Female patients of childbearing potential who are sexually active and unwilling to use a medically acceptable method of contraception during the trial and for  months after the last administration of BI , i.e. combination of two forms of effective contraception (defined as hormonal contraception, intrauterine device, transdermal patch, implantable or injectable contraceptive, bilateral tubal ligation etc.).
At a minimum, subjects must agree to the use of two methods of contraception, with one method being highly effective and the other method being either highly effective or less effective as listed below:\r\n* HIGHLY EFFECTIVE METHODS OF CONTRACEPTION\r\n** Male condoms with spermicide\r\n** Hormonal methods of contraception including combined oral contraceptive pills, vaginal ring, injectables, implants, and intrauterine devices (IUDs) such as Mirena by WOCBP subjects or male subjects WOCBP partner; female partners of male subjects participating in the study may use hormone based contraceptives as one of the acceptable methods of contraception since they will not be receiving study drug\r\n** Progestogen only hormonal contraception associated with inhibition of ovulation\r\n** Intrauterine hormone-releasing system (IUS)\r\n** Nonhormonal IUDs, such as ParaGard\r\n** Tubal ligation\r\n** Vasectomy\r\n** Complete Abstinence - complete abstinence is defined as complete avoidance of heterosexual intercourse and is an acceptable form of contraception for all study drugs; subjects who choose complete abstinence are not required to use a second method of contraception, but female subjects must continue to have pregnancy tests; acceptable alternate methods of highly effective contraception must be discussed in the event that the subject chooses to forego complete abstinence\r\n* LESS EFFECTIVE METHODS OF CONTRACEPTION\r\n** Diaphragm with spermicide\r\n** Cervical cap with spermicide\r\n** Vaginal sponge\r\n** Male Condom without spermicide\r\n** Progestin only pills by WOCBP subjects or male subjects WOCBP partner\r\n** Female condom - a male and female condom must not be used together\r\n* UNACCEPTABLE METHODS OF CONTRACEPTION\r\n** Periodic abstinence (calendar, symptothermal, post-ovulation methods)\r\n** Withdrawal (coitus interruptus)\r\n** Spermicide only\r\n** Lactation amenorrhea method (LAM)\r\n* NOTE: azoospermic males and WOCBP who are continuously not heterosexually active are exempt from contraceptive requirements; however, WOCBP participants must still undergo pregnancy testing as described
Women of child bearing potential (WCBP), defined as a sexually mature woman not surgically sterilized or not post-menopausal for at least  consecutive months if =<  years or  months if >  years, must have a negative serum pregnancy test within  hours prior to the first dose of study drug and must agree to use highly effective methods of birth control throughout the study; highly effective methods of contraception include total abstinence, sterilization of patient and/or patients partner, or use of combination of two methods, including barrier methods (double barrier method is acceptable), intrauterine device (IUD) or intrauterine system (IUS), and hormonal implants or combined oral contraceptives
Participants of childbearing potential (as defined above) must be willing to use effective contraception during treatment and up to  months after stop of trial treatment. Acceptable methods of contraception are intrauterine devices, bilateral tubal occlusion, vasectomized, or total abstinence. Oral, injectable, or implant hormonal contraceptives are not allowed.
Appropriate contraception should be used from the time of screening, throughout the duration of study participation, and for four months after the last dose of AZD; acceptable methods of contraception include abstinence, tubal ligation, intra-uterine devices, and vasectomized partner; all methods of contraception (with the exception of total abstinence) should be used in combination with the use of a condom by the male sexual partner for intercourse; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, the participants treating physician should be informed immediately; additionally, male patients should refrain from donating sperm from the start of dosing until  months after discontinuing AZD; if male patients wish to father children they should be advised to arrange for freezing of sperm samples prior to the start of study treatment
Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through  days after the last dose of trial treatment; women of childbearing potential (WOCBP) should agree to methods of contraception described in the protocol; WOCBP is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal; menopause is defined clinically as  months of amenorrhea in a woman over  in the absence of other biological or physiological causes; in addition, women under the age of  must have a documented serum follicle stimulating hormone (FSH) level >  mIU/mL; women of childbearing potential (WOCBP) receiving nivolumab will be instructed to adhere to contraception for a period of  weeks after the last dose of investigational product; men receiving nivolumab and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of  weeks after the last dose of investigational product; these durations have been calculated using the upper limit of the half-life for nivolumab ( days); and are based on the protocol requirement that WOCBP use contraception for  half-lives plus  days and men who are sexually active with WOCBP use contraception for  half-lives plus  days; *HIGHLY EFFECTIVE METHODS OF CONTRACEPTION:\r\n** Male condoms with spermicide\r\n** Hormonal methods of contraception including combined oral contraceptive pills, vaginal ring, injectables, implants and intrauterine devices (IUDs) such as Mirena by WOCBP subject or male subjects WOCBP partner female partners of male subjects participating in the study may use hormone based contraceptives as one of the acceptable methods of contraception since they will not be receiving study drug\r\n** Non-hormonal IUDs, such as ParaGard \r\n** Tubal ligation\r\n** Vasectomy\r\n** Complete abstinence; complete abstinence is defined as complete avoidance of heterosexual intercourse and is an acceptable form of contraception for all study drugs; subjects who choose complete abstinence are not required to use a second method of contraception, but female subjects must continue to have pregnancy tests; acceptable alternate methods of highly effective contraception must be discussed in the event that the subject chooses to forego complete abstinence\r\n* LESS EFFECTIVE METHODS OF CONTRACEPTION:\r\n** Diaphragm with spermicide\r\n** Cervical cap with spermicide\r\n** Vaginal sponge\r\n** Male condom without spermicide\r\n** Progestin only pills by WOCBP subject or male subjects WOCBP partner\r\n** Female condom; a male and female condom must not be used together
Women of child-bearing potential, defined as all women capable of becoming pregnant, unless they are using two effective methods of contraception (unless patient is practicing total abstinence) during dosing and for  days after last dose, i.e., final vaccine; effective contraception methods include:\r\n* Female sterilization at least eight weeks before taking study treatment\r\n* Male sterilization (at least six months prior to screening)\r\n* Use of oral, injected or implanted hormonal methods of contraception or placement of an intrauterine device or other forms of hormonal contraception that have comparable efficacy (failure rate < %); in case of use of oral contraception, women should have been stable on the same pill for a minimum of  months before taking study treatment
At a minimum, subjects must agree to the use of two methods of contraception, with one method being highly effective and the other method being either highly effective or less effective as listed below: \r\n* Highly effective methods of contraception\r\n** Male condoms with spermicide\r\n** Hormonal methods of contraception including combined oral contraceptive pills, vaginal ring, injectables, implants, and intrauterine devices (IUDs) such as Mirena by WOCBP subjects or male subjects WOCBP partner.\r\n** Nonhormonal IUDs, such as ParaGard\r\n** Tubal ligation\r\n** Vasectomy.\r\n**Complete Abstinence*\r\n*** Complete abstinence is defined as complete avoidance of heterosexual intercourse and is an acceptable form of contraception for all study drugs. Subjects who choose complete abstinence are not required to use a second method of contraception, but female subjects must continue to have pregnancy tests. Acceptable alternate methods of highly effective contraception must be discussed in the event that the subject chooses to forego complete abstinence. \r\n* Less effective methods of contraception\r\n** Diaphragm with spermicide\r\n** Cervical cap with spermicide\r\n** Vaginal sponge\r\n** Male Condom without spermicide\r\n*** A male and female condom must not be used together\r\n** Progestin only pills by WOCBP subjects or male subjects WOCBP partner\r\n** Female Condom\r\n*** A male and female condom must not be used together
Women of childbearing potential must have a negative serum or urine pregnancy\r\n* NOTE: Women of childbearing potential is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal. Menopause is defined clinically as  months of amenorrhea in a woman over  in the absence of other biological or physiological causes. In addition, women under the age of  must have a documented serum follicle stimulating hormone (FSH) level less than  mIU/mL\r\n* NOTE: Women of childbearing potential (WOCBP) receiving nivolumab will be instructed to adhere to contraception for a period of  months after the last dose of investigational product. Men receiving nivolumab and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of  months after the last dose of investigational product. These durations have been calculated using the upper limit of the half-life for nivolumab ( days) and are based on the protocol requirement that WOCBP use contraception for  half-lives plus  days and men who are sexually active with WOCBP use contraception for  half-lives plus  days\r\n* HIGHLY EFFECTIVE METHODS OF CONTRACEPTION\r\n** Male condoms with spermicide\r\n** Hormonal methods of contraception including combined oral contraceptive pills, vaginal ring, injectables, implants and intrauterine devices (IUDs) such as Mirena by WOCBP subject or male subjects WOCBP partner. Female partners of male subjects participating in the study may use hormone based contraceptives as one of the acceptable methods of contraception since they will not be receiving study drug\r\n** Nonhormonal IUDs, such as ParaGard\r\n** Tubal ligation\r\n** Vasectomy\r\n** Complete Abstinence\r\n***Complete abstinence is defined as complete avoidance of heterosexual intercourse and is an acceptable form of contraception for all study drugs. Subjects who choose complete abstinence are not required to use a second method of contraception, but female subjects must continue to have pregnancy tests. Acceptable alternate methods of highly effective contraception must be discussed in the event that the subject chooses to forego complete abstinence\r\n* LESS EFFECTIVE METHODS OF CONTRACEPTION\r\n** Diaphragm with spermicide\r\n** Cervical cap with spermicide\r\n** Vaginal sponge\r\n** Male Condom without spermicide\r\n** Progestin only pills by WOCBP subject or male subjects WOCBP partner\r\n** Female condom (a male and female condom must not be used together)
Females of childbearing potential: \r\n* Must not be breast feeding;\r\n* Must have a negative serum or urine pregnancy test; \r\n* Must agree to use adequate contraception for a minimum of two weeks prior to receiving study medication until  months after discontinuation of the study medication. \r\n** NOTE: Acceptable methods of contraception include total and true sexual abstinence, hormonal contraceptives that are not prone to drug-drug interactions (IUS levonorgestrel intra uterine system [Mirena], medroxyprogesterone injections [Depo-Provera]), copper-banded intra-uterine devices, and vasectomized partner. All hormonal methods of contraception should be used in combination with the use of a condom by their sexual male partner. Females of childbearing potential are defined as those who are not surgically sterile (ie, bilateral tubal ligation, bilateral oophorectomy, or complete hysterectomy) or postmenopausal (defined as  months with no menses without an alternative medical cause)
Women of childbearing potential (WOCBP) and men must agree to use adequate contraception prior to study entry and for the duration of study participation and for  days after the last dose of therapy; highly effective contraceptive measures include: stable use of oral contraceptives such as combined estrogen and progestogen and progestogen only hormonal contraception or other prescription pharmaceutical contraceptives for  or more menstrual cycles prior to screening; intrauterine device (IUD); intrauterine hormone releasing system (IUS); bilateral tubal ligation; vasectomy and sexual abstinence\r\n* WOCBP must have a negative serum or urine pregnancy test within  days of initiation of dosing\r\n* Contraception is not required for men with documented vasectomy\r\n* Postmenopausal women must be amenorrheic for at least  months in order not to be considered of childbearing potential\r\n* Pregnancy testing and contraception are not required for women with documented hysterectomy or tubal ligation
Female subjects of childbearing potential and their male partners, and male subjects must be willing to use a highly effective method of contraception from the time consent is signed until  months after treatment discontinuation; highly effective forms of contraception include complete sexual abstinence or use of a condom plus an additional contraceptive method that together result in a failure rate of < % per year; barrier methods (ex: condom) used alone, periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception
Women of childbearing potential and fertile men who are sexually active must agree to use a highly effective method of contraception (less than [<]  percent [%] / year failure rate) during the study and for  days after the last dose of study drug. Contraception must be consistent with local regulations regarding the use of birth control methods for participants participating in clinical trials. When a woman is of childbearing potential the following are required: Participants must agree to practice a highly effective method of contraception (failure rate of <% per year when used consistently and correctly). Examples of highly effective contraceptives for women include user-independent methods (for example, implantable progestogen-only hormone contraception associated with inhibition of ovulation; intrauterine device; intrauterine hormone-releasing system; vasectomized partner) and user-dependent methods (for example: combined [estrogen- and progestogen-containing] hormonal contraception associated with inhibition of ovulation [oral/intravaginal/ transdermal]; progestogen-only hormone contraception associated with inhibition of ovulation [oral/injectable]. In addition to the highly effective method of contraception, a man who is sexually active with a woman of childbearing potential must agree to use a barrier method of contraception (for example a condom with spermicidal foam/gel/film/cream/suppository). Additionally, a man who is sexually active with a woman who is pregnant must use a condom. Women and men must agree not to donate eggs (ova, oocytes) or sperm, respectively, during the study and for  days after the last dose of study drug
At a minimum, subjects must agree to the use of two methods of contraception, with one method being highly effective and the other method being either highly effective or less effective as listed below:\r\n* HIGHLY EFFECTIVE METHODS OF CONTRACEPTION\r\n** Hormonal methods of contraception including combined oral contraceptive pills, vaginal ring, injectables, implants and intrauterine devices (IUDs) by WOCBP subject or male subjects WOCBP partner\r\n** Nonhormonal IUDs \r\n** Tubal ligation \r\n** Vasectomy\r\n** Complete abstinence\r\n*** Complete abstinence is defined as complete avoidance of heterosexual intercourse and is an acceptable form of contraception for all study drugs; subjects who choose complete abstinence are not required to use a second method of contraception, but female subjects must continue to have pregnancy tests; acceptable alternate methods of highly effective contraception must be discussed in the event that the subject chooses to forego complete abstinence\r\n* LESS EFFECTIVE METHODS OF CONTRACEPTION\r\n** Diaphragm with spermicide \r\n** Cervical cap with spermicide \r\n** Vaginal sponge \r\n** Male condom without spermicide \r\n** Male condoms with spermicide \r\n** Progestin only pills by WOCBP subject or male subjects WOCBP partner \r\n** Female condom\r\n*** A male and female condom must not be used together
If fertile, willing to use highly effective form of contraception (defined as a combination of at least two of the following methods: condom or other barrier methods, oral contraceptives, implantable contraceptives, intrauterine devices) during the dosing period and for at least  months after the dosing period
Patients with reproductive potential must be willing to use, in combination with her partner,  acceptable methods of effective contraception or practice sexual abstinence throughout the study and continue for  months after study duration; subjects who are surgically sterile (e.g., history of bilateral tubal ligation, hysterectomy) or whose sexual partner is sterile (e.g., history of vasectomy) are not required to use additional contraceptive measures
At a minimum, subjects must agree to use one highly effective (which have a failure rate of < % when used consistently and correctly) OR one less effective method of contraception as listed below:\r\n* WOCBP and female partners of male subjects, who are WOCBP, are expected to use one of the highly effective methods of contraception listed below; male subjects must inform their female partners who are WOCBP of the contraceptive requirements of the protocol and are expected to adhere to using contraception with their partner; contraception methods are as follows:\r\n** Progestogen only hormonal contraception associated with inhibition of ovulation\r\n** Hormonal methods of contraception including oral contraceptive pills containing combined estrogen + progesterone, vaginal ring, injectables, implants and intrauterine devices (IUDs) such as Mirena\r\n** Nonhormonal IUDs, such as ParaGard\r\n** Bilateral tubal occlusion\r\n** Vasectomised partner with documented azoospermia  days after procedure\r\n** Intrauterine hormone-releasing system (IUS)\r\n** Complete abstinence\r\n* Less effective methods of contraception\r\n** Diaphragm with spermicide\r\n** Cervical cap with spermicide\r\n** Vaginal sponge with spermicide\r\n** Male or female condom with or without spermicide\r\n** Progestogen-only oral hormonal contraception, where inhibition of ovulation is not the primary mode of action\r\n* Unacceptable methods of contraception\r\n** Periodic abstinence (calendar, symptothermal, post-ovulation methods)\r\n** Withdrawal (coitus interruptus)\r\n** Spermicide only\r\n** Lactation amenorrhea method (LAM)
Females of child-bearing potential should use reliable methods of contraception from the time of screening until  months after discontinuing osimertinib; acceptable methods of contraception include total and true sexual abstinence, tubal ligation, hormonal contraceptives that are not prone to drug-drug interactions (intra uterine system [IUS] levonorgestrel intra uterine system (Mirena), medroxyprogesterone injections (Depo-Provera), copper-banded intra-uterine devices, and vasectomized partner; all hormonal methods of contraception should be used in combination with the use of a condom by their male sexual partner for intercourse
Female patients who are of child-bearing potential (as defined above) should use enhanced methods of contraception from the time of screening until  days after the final dose of study drug; cessation of birth control after this point should be discussed with a responsible physician; acceptable methods of contraception include true abstinence in line with the preferred and usual lifestyle choice of the subject, tubal ligation, vasectomized partner, and methods listed in the table below; all methods of contraception (with the exception of total abstinence) should be used in combination with the use of a condom by their male sexual partner for intercourse; periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of birth control; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
All female subjects of child bearing age must be either surgically sterile, postmenopausal for at least  year, or using an acceptable method of contraception; examples of adequate methods of contraception include abstinence, intrauterine device, hormonal contraception, use of spermicide and a condom by sexual partner, or partner with a vasectomy; adequate contraception must be used from the beginning of the screening period until at least  weeks after the last dose of KW-; male subjects with partners of childbearing potential must use a barrier method of contraception from the day of the first dose of KW- until at least  weeks after the last dose
Male subjects must agree to use one of the contraception methods listed below; this criterion must be followed from the time of the first dose of study medication until  weeks after the last dose of study medication; however, it is advised that contraception be used for a total of  weeks following the last dose; methods: a) abstinence, defined as sexual inactivity consistent with the preferred and usual lifestyle of the subject; periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception; b) condom (during non-vaginal intercourse with any partner - male or female) OR c) condom and occlusive cap (diaphragm or cervical/vault caps) plus spermicidal agent (foam/gel/film/cream/suppository) (during sexual intercourse with a female)
Male subject's using contraception should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. Males are eligible to participate if they as detailed below: Agree to use a male condom and female partner to use an additional highly effective contraceptive method with a failure rate of <% per year when having sexual intercourse with a WOCBP who is not currently pregnant.
Continued sexual activity in men** or women of childbearing potential*** who are unwilling to practice highly effective contraception during the study and until  months after the last dose of study drug (highly effective contraceptive measures include stable use of oral contraceptives such as combined estrogen and progestogen and progestogen only hormonal contraception or other prescription pharmaceutical contraceptives for  or more menstrual cycles prior to screening; intrauterine device [IUD]; intrauterine hormone-releasing system [IUS]; bilateral tubal ligation; vasectomy, and sexual abstinence). (**Contraception is not required for men with documented vasectomy ***Postmenopausal women must be amenorrheic for at least  months in order not to be considered of childbearing potential. Pregnancy testing and contraception are not required for women with documented hysterectomy or tubal ligation.)
Individuals of reproductive potential and their partners willing to practice total abstinence or use a highly effective method of contraception (failure rate < % per year) during treatment and for  months following the last dose of rucaparib; the following are allowable only:\r\n* Ongoing use of progesterone-only injectable or implantable contraceptives (eg, Depo Provera, Implanon, Nexplanon)\r\n* Placement of an intrauterine device or intrauterine system\r\n* Bilateral tubal occlusion\r\n* Sterilization, with appropriate post-vasectomy documentation of absence of sperm in ejaculate\r\n* True, complete (as opposed to periodic) abstinence
Negative pregnancy test done =<  hours prior to registration for women of childbearing potential only; Note: all female subjects will be considered to be of child-bearing potential unless they are postmenopausal (at least  months consecutive amenorrhea, in the appropriate age group and without other known or suspected cause), or have been sterilized surgically (i.e., bilateral tubal ligation >=  menstrual cycle prior to randomization, or have undergone a hysterectomy and/or bilateral oophorectomy)\r\n* All female subjects will be considered to be of child-bearing potential unless they are postmenopausal (at least  months consecutive amenorrhea, in the appropriate age group and without other known or suspected cause), or have been sterilized surgically (i.e., bilateral tubal ligation >=  menstrual cycle prior to randomization, or have undergone a hysterectomy and/or bilateral oophorectomy); female subjects of child-bearing potential must agree to use highly effective contraception during the study treatment and for  months after the final dose of study treatment; female subjects exempt from this requirement are subjects who practice total abstinence; if currently abstinent, the subject must agree to use a double barrier method of contraception (i.e., condom and occlusive cap [diaphragm or cervical/vault caps]) with spermicide or until they are established on highly effective contraception for at least one menstrual cycle if they become sexually active during the study treatment and for  months after the final dose of study treatment\r\n* Highly effective contraception includes:\r\n** Placement of intrauterine device or system\r\n** Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault cap) with spermicide\r\n** Vasectomized partner with confirmed azoospermia\r\n* Male subjects and their female partner who are of child-bearing potential (as defined above), and are not practicing total abstinence, must agree to use highly effective contraception during study treatment and for  months after the final dose of study treatment; if currently abstinent, the subject must agree to use a double barrier method of contraception if they become sexually active, or until they are established on highly effective contraception as described above
Subjects with reproductive potential must be willing to use, in combination with his/her partner,  highly effective methods of effective contraception or practice sexual abstinence throughout the study and continue for  months after the study duration; subjects who are surgically sterile (e.g. history of bilateral tubal ligation, hysterectomy) or whose sexual partner is sterile (e.g. history of vasectomy) are not required to use additional contraceptive measures
At a minimum, participants must agree to the use of one highly effective method of contraception as listed below:\r\n* Highly effective methods of contraception have a failure rate of < % when used consistently and correctly; WOCBP participants and female partners of male participants who are WOCBP are expected to use one of the highly effective methods of contraception listed below; male participants must inform their female partners who are WOCBP of the contraceptive requirements of the protocol and are expected to adhere to using contraception with their partner; contraception methods are as follows:\r\n** Progestogen-only hormonal contraception associated with inhibition of ovulation\r\n** Hormonal methods of contraception, including oral contraceptive pills containing combined estrogen + progesterone, vaginal ring, injectables, implants, and intrauterine devices (IUDs) such as Mirena\r\n** Nonhormonal IUDs, such as ParaGard\r\n** Bilateral tubal occlusion\r\n** Vasectomized partner with documented azoospermia  days after procedure\r\n*** Vasectomized partner is a highly effective birth control method provided that partner is the sole sexual partner of the WOCBP trial participant and that the vasectomized partner has received medical assessment of the surgical success\r\n** Intrauterine hormone-releasing system (IUS)\r\n** Complete abstinence\r\n*** Complete abstinence is defined as the complete avoidance of heterosexual intercourse\r\n*** Complete abstinence is an acceptable form of contraception for all study drugs and must be used throughout the duration of the study treatment (plus  half-lives of the investigational drug plus  days);\r\n*** It is not necessary to use any other method of contraception when complete abstinence is elected;\r\n*** Participants who choose complete abstinence must continue to have pregnancy tests\r\n*** Acceptable alternate methods of highly effective contraception must be discussed in the event that the participant chooses to forego complete abstinence\r\n*** The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the participant\r\n* UNACCEPTABLE METHODS OF CONTRACEPTION\r\n** Periodic abstinence (calendar, symptothermal, post-ovulation methods)\r\n** Spermicide only\r\n** Lactation amenorrhea method (LAM)
Women of child-bearing potential and men must agree to use adequate contraception prior to study entry, for the duration of study participation, and up to  days following completion of therapy; for women this should include one highly effective method of contraception and one barrier method as defined below\r\n* Highly effective methods include:\r\n** Total abstinence from sexual intercourse (minimum one complete menstrual cycle prior to study drug administration);\r\n** Vasectomized partner;\r\n** Medroxyprogesterone acetate depot injection;\r\n** Placement of a copper-banded intrauterine device (IUD) or intrauterine system (IUS);\r\n** Bilateral tubal ligation;\r\n* Barrier methods include:\r\n** Condom;\r\n**Occlusive cap (e.g. diaphragm or cervical/vault caps) with spermicide\r\n* Please note: use of other oral, injected or implanted hormonal methods of contraception cannot be considered highly effective as it is currently unknown whether vistusertib may reduce their effectiveness; periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of contraception\r\n* Additionally, male subjects (including those who are vasectomized) whose partners are pregnant or might be pregnant must agree to use condoms for the duration of the study and for  days following completion of therapy
HIGHLY EFFECTIVE METHODS OF CONTRACEPTION\r\n* Male condoms with spermicide\r\n* Hormonal methods of contraception including combined oral contraceptive pills, vaginal ring, injectables, implants and intrauterine devices (IUDs) such as Mirena by WOCBP subject or male subjects WOCBP partner. Female partners of male subjects participating in the study may use hormone based contraceptives as one of the acceptable methods of contraception since they will not be receiving study drug\r\n* Nonhormonal IUDs, such as ParaGard\r\n* Tubal ligation\r\n* Vasectomy\r\n* Complete abstinence\r\n** Complete abstinence is defined as complete avoidance of heterosexual intercourse and is an acceptable form of contraception for all study drugs. Subjects who choose complete abstinence are not required to use a second method of contraception, but female subjects must continue to have pregnancy tests. Acceptable alternate methods of highly effective contraception must be discussed in the event that the subject chooses to forego complete abstinence.
Women of child-bearing potential and men must agree to use adequate contraception prior to study entry, for the duration of study participation and for  months after study participation; acceptable methods of contraception include hormonal, barrier methods, intrauterine device, tubal ligation/vasectomy or abstinence; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; acceptable methods of contraception include hormonal, barrier methods, intrauterine device, tubal ligation/vasectomy or abstinence; women should not breast feed while on treatment with MK- and hydroxychloroquine
Female subjects in child bearing age must be using acceptable contraception methods such as hormonal contraception or two forms of barrier contraception. Acceptable contraception must be used consistently from  days before screening until  years following surgery Exclusion Criteria: Pre-operative exclusion criteria:
Women of child-bearing potential (according to recommendations of the Clinical Trial Facilitation Group [CTFG]; see protocol for details) must not be pregnant or breastfeeding and must have a negative pregnancy test at screening. Women of child-bearing potential and men with female partners of child-bearing potential must agree to practice  highly effective contraceptive measures of birth control (as described in the protocol) and must agree not to become pregnant or father a child while receiving treatment with study drug and for at least  months after completing treatment. Contraceptive measures which may be considered highly effective comprise combined hormonal contraception (oral, vaginal, or transdermal) or progestogen-only hormonal contraception (oral, injectable, implantable) associated with inhibition of ovulation, intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion, sexual abstinence, and surgically successful vasectomy. Abstinence is acceptable only if it is consistent with the preferred and usual lifestyle of the subject. Periodic abstinence (eg, calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of birth control.
Women of childbearing potential must agree and commit to the use of a highly effective non-hormonal method of contraception, ie, intrauterine device, bilateral tubal ligation, vasectomized partner, or abstinence (only when it is the preferred lifestyle of the patient), from the time of informed consent until  days after the last dose of the investigational products. Men and their female partners of childbearing potential must agree and commit to use a highly effective method of contraception (ie, any of the above methods or hormonal contraception associated with inhibition of ovulation) while on treatment and for  months after last dose of investigational products
Women of child-bearing potential should use reliable methods of contraception from the time of screening until  months after discontinuing study treatment; acceptable methods of contraception include tubal ligation, tricycle combined oral or transdermal contraceptives, copper-banded intra-uterine devices and vasectomized partner; hormonal contraceptives should be combined with a barrier method of contraception; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; women of child-bearing potential must have a negative pregnancy test prior to entry; male patients should use reliable methods of contraception such as barrier contraception i.e. condoms during sexual activities with women of child-bearing potential and refrain from sperm donation during the trial and for a washout period of at least  months; if male patients wish to father children they should be advised to arrange for freezing of sperm samples prior to the start of study treatment
Males and females of childbearing potential are permitted in the study so long as they consent to avoid getting their partner pregnant or becoming pregnant, respectively, by using a highly effective contraception method, as described below, throughout the study and for up to  days after completion. Highly effective methods of contraception include: intra-uterine device (nonhormonal or hormonal), bilateral tubal occlusion, vasectomy, sexual abstinence, or barrier methods (e.g., condom, diaphragm) used in combination with hormonal methods associated with inhibition of ovulation. Women of non-childbearing potential may be included if they are either surgically sterile or have been postmenopausal for ?  year. Women who have documentation of at least  months of spontaneous amenorrhea and have an FSH level >  mIU/mL will be considered postmenopausal.
Females of child-bearing potential: willing to use two forms of effective contraception, and to continue use for  weeks ( months) post last dose of study medication; effective contraception is defined as:\r\n* An intrauterine device with a documented failure rate of less than % per year\r\n* Male partner sterilization prior to the female subjects entry, and this male is the sole sexual partner for that female\r\n* Complete abstinence from sexual intercourse for  days prior to enrollment, throughout study treatment, and for at least  months after the last dose of study treatment; abstinence is only acceptable when in line with the preferred and usual lifestyle of the subject; periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods, etc) and withdrawal are not acceptable methods of contraception\r\n* Double-barrier contraception: condom and occlusive cap (diaphragm or cervical/vault caps) with a vaginal spermicidal agent (foam/gel/cream/suppository)\r\nNote: hormonal-based methods (e.g., oral contraceptives) are not permitted as contraception; female subjects who are lactating must discontinue nursing prior to the first dose of study treatment and must refrain from nursing throughout the treatment period and for  months following the last dose of study treatment; females of non-childbearing potential are those who are postmenopausal (defined as greater than  year without menses with an appropriate clinical profile, e.g., age appropriate, >  years in the absence of hormone-replacement therapy (HRT); in questionable cases, the subject must have a follicle-stimulating hormone (FSH) value >  mIU/mL and an estradiol value <  pg/mL (<  pmol/L); or who have had a bilateral tubal ligation or tubal occlusion, bilateral oophoredtomy or hysterectomy; men with a female partner of childbearing potential must have either had a prior vasectomy or agree to use effective contraception as described from D of treatment, throughout the treatment period, and for  weeks after the last dose of study treatment; if a subject becomes pregnant during the treatment period of the study, the study treatments should be stopped immediately
Female patients of childbearing potential are required to have a negative serum pregnancy test within  days prior to the first dose of study medication\r\n* Females are required to use an effective method of contraception from the time of negative serum pregnancy test, throughout the study duration, and for  months after the last dose of study medication; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; men treated or enrolled on this protocol must also agree to use adequate contraception prior to study enrollment, for the duration of study participation, and for  weeks after completion of the last dose of study drug\r\n* Specific contraception requirements for females: female subjects of childbearing potential must not become pregnant and are required to be sexually inactive by abstinence or use contraceptive methods with a failure rate of < %; sexual inactivity by abstinence must be consistent with the preferred and usual lifestyle of the subject; periodic abstinence (e.g. calendar, ovulation, symptothermal, post ovulation methods) and withdrawal are not acceptable methods of contraception; contraceptive methods with a failure rate of < % include the following: \r\n** Intrauterine device (IUD) or intrauterine system (IUS) that meets the < % failure rate as stated in the product label\r\n** Male partner sterilization (vasectomy with documentation of azoospermia) prior to the female subject's entry into the study, and this male is patient's sole sexual partner; for this definition, \documented\ refers to the outcome of the investigator's/qualified physician designee's medical examination of the subject or review of the subject's medical history for study eligibility, as obtained via a verbal interview with the subject or from the subject's medical records\r\n** Double barrier method: condom and occlusive cap (diaphragm or cervical/vault caps) plus spermicidal agent (foam/gel/film/cream/suppository); these allowed methods of contraception are only effective when used consistently, correctly and in accordance with the product label; the investigator is responsible for ensuring subjects understand how to properly use these methods of contraception\r\n* Specific contraception requirements for males: to prevent pregnancy in a female partner or to prevent exposure of any partner to the investigational product from a male subject's semen, male subjects must use one of the following contraceptive methods during the study and for a total of  weeks following the last dose of study drug (based upon the lifecycle of sperm): \r\n** Abstinence, defined as sexual inactivity consistent with the preferred and usual lifestyle of the subject for  days prior to first dose of study drug, through the dosing period, and for at least  weeks after the last dose of study drug; periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception\r\n** Condom (during non-vaginal intercourse with any partner - male or female) OR \r\n** Condom and occlusive cap (diaphragm or cervical/vault caps) plus spermicidal agent (foam/gel/film/cream/suppository) (during sexual intercourse with a female)
Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, must have a negative serum pregnancy test before initiation of study treatment and must also use highly effective methods of contraception while enrolled in the study. The use of highly effective contraception should continue for at least  days after the last dose of study treatment or until the last day of TFR/TFR-, or for the duration of a monthly cycle of oral contraception, whichever is longer. Acceptable forms of highly effective contraception methods include: a. Total abstinence (when this is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception and male/female sterilization defined as:
Patients of childbearing or child fathering potential must be willing to use an acceptable method of birth control prior to study entry and for the duration of the study; acceptable methods of contraception include hormonal, barrier methods, intrauterine device, tubal ligation/vasectomy or abstinence
A highly effective method of contraception is defined as one that results in a low failure rate (ie, less than % per year) when used consistently and correctly. Acceptable methods of contraception are described in Table ..-. Sustained abstinence is an acceptable practice; however, periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of contraception
Female subjects of child-bearing potential who are unwilling to use highly effective contraception (e.g., combined (estrogen and progestogen containing) or progestogen-only hormonal contraceptives, intrauterine devices, bilateral tubal ligation, vasectomized partner, sexual abstinence or equivalent measures) for the duration of study treatment
Before enrollment, a woman must be one of the following:\r\n* Not of childbearing potential, defined as:\r\n** Postmenopausal (>  years of age with amenorrhea for at least  months or any age with amenorrhea for at least  months and a serum follicle stimulating hormone [FSH] level >  IU/mL)\r\n** Permanently sterilized (e.g., tubal occlusion, hysterectomy, bilateral salpingectomy) \r\n** Otherwise be incapable of pregnancy\r\n* Of childbearing potential and practicing a highly effective method of birth control (consistent with local regulations regarding the use of birth control methods for subjects participating in clinical studies) during the study and for  months after receiving the last dose of study agent NOTE: Examples include established use of oral, injected or implanted hormonal methods of contraception; placement of an intrauterine device (IUD) or intrauterine system (IUS); barrier methods: condom with spermicidals (including foam/gel/film/cream/suppository) or occlusive cap (diaphragm or cervical/vault caps) with spermicidals; male partner sterilization (the vasectomized partner should be the sole partner for that subject); true abstinence (when this is in line with the preferred and usual lifestyle of the subject); Note: If the childbearing potential changes after start of the study (e.g., woman who is not heterosexually active becomes active) a woman must begin a highly effective method of birth control, as described above
At a minimum, subjects must agree to the use of one method of highly effective contraception as listed below:\r\n* HIGHLY EFFECTIVE METHODS OF CONTRACEPTION\r\n** Male condoms with spermicide\r\n** Hormonal methods of contraception including combined oral contraceptive pills, vaginal ring, injectables, implants and intrauterine devices (IUDs) such as Mirena by WOCBP subject or male subjects WOCBP partner\r\n** Female partners of male subjects participating in the study may use hormone based contraceptives as one of the acceptable methods of contraception since they will not be receiving study drug\r\n** IUDs, such as ParaGard\r\n** Tubal ligation\r\n** Vasectomy\r\n** Complete abstinence\r\n*** Complete abstinence is defined as complete avoidance of heterosexual intercourse and is an acceptable form of contraception for all study drugs; female subjects must continue to have pregnancy tests; acceptable alternate methods of highly effective contraception must be discussed in the event that the subject chooses to forego complete abstinence
Women of child-bearing potential (WOCBP) and men able to father a child must agree to use highly effective contraception while on study drug and for  days after the last dose of avelumab; WOCBP must have a negative pregnancy test within  days of initiation of dosing; highly effective contraceptive measures include: stable use of oral contraceptives such as combined estrogen and progestogen and progestogen only hormonal contraception or other prescription pharmaceutical contraceptives for  or more menstrual cycles prior to screening; intrauterine device (IUD); intrauterine hormone-releasing system (IUS); bilateral tubal ligation; vasectomy and sexual abstinence\r\n* Contraception is not required for men with documented vasectomy\r\n* Postmenopausal women must be amenorrheic for at least  months in order not to be considered of childbearing potential\r\n* Pregnancy testing and contraception are not required for women with documented hysterectomy or tubal ligation
Women of child-bearing potential and men must agree to use adequate contraception prior to the study entry, for the duration of study participation and up to  weeks following completion of therapy\r\n* Acceptable contraception includes:\r\n** Total abstinence from sexual intercourse \r\n** Surgically sterilized subject or partner (i.e. male vasectomy, tubal ligation, female hysterectomy or bilateral oophorectomy)\r\n** Use of  of the following:\r\n*** Barrier methods: diaphragm, condom (by the partner), copper intrauterine device, sponge, or spermicide\r\n*** Hormonal contraception (pills, patch, intrauterine device, or injections)