Patients must have histologically documented solid tumors or histologically confirmed diagnosis of lymphoma or multiple myeloma requiring therapy and meet one of the following criteria:\r\n* Patients must have progressed following at least one line of standard systemic therapy and there must not be other approval/standard therapy available that has been shown to prolong overall survival (i.e. in a randomized trial against another standard treatment or by comparison to historical controls); patients who cannot receive other standard therapy that has been shown to prolong overall survival due to medical issues will be eligible, if other eligibility criteria are met; if the patient is currently receiving therapy, the clinician must have assessed that the current therapy is no longer benefitting the patient prior to enrolling on MATCH, regardless of whether it is considered standard OR\r\n* Patients for whose disease no standard treatment exists that has been shown to prolong overall survival\r\n* NOTE: No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer; in situ cervical cancer; adequately treated stage I or II cancer from which the patient is currently in complete remission; any other cancer from which the patient has been disease-free for 5 years
Patients must have progressed following at least one line of standard systemic therapy and there must not be other approved/standard therapy available that has been shown to prolong overall survival (i.e. in a randomized trial against another standard treatment or by comparison to historical controls); patients who cannot receive other standard therapy that has been shown to prolonged survival due to medical issues will be eligible, if other eligibility criteria are met; OR \r\n* Patients for whose disease no standard treatment exists that has been shown to prolong overall survival
Patient must meet at least one of the following criteria: a. Progressed or recurrent despite standard therapy, b. No standard therapy exists for this malignancy, c. Patient is intolerant of standard therapy, d. Patient is not a candidate for standard therapy, e. For AML and MDS patients: patient is not a candidate for allogeneic hematopoietic stem cell transplantation, f, For sarcoma patients: f-1. Patient has disease that is metastatic or unresectable, f-2. Patient with metastatic disease has had at least one prior line of therapy for metastatic disease, f-3. No curative multimodality options exist
Phase I part: Patients with advanced/metastatic solid tumors, with measurable or non-measurable disease as determined by RECIST version 1.1 (refer to Appendix 1), who have progressed despite standard therapy or are intolerant of standard therapy, or for whom no standard therapy exists.
2. Part A, must have a histologically or cytologically documented, incurable, or metastatic solid tumor that has progressed on, or been intolerant to, all standard systemic therapy options for the tumor type in the metastatic setting, or must have a tumor type for which no such standard systemic option exists;
Subjects with histological- or cytological-confirmed, advanced cancer, who have progressed on (or not been able to tolerate) standard therapy or for whom no standard anticancer therapy exists
Participants must have received, and then progressed, relapsed, or been intolerant to, at least 1 standard treatment regimen in the advanced or metastatic setting according to solid tumor histologies
Participants must have received and then progressed or been intolerant to at least 1 standard treatment regimen in the advanced or metastatic setting if such a therapy exists
Must have progressed following standard therapy, or for whom, in the opinion of the Investigator, no effective standard therapy exists, is tolerated or is appropriate.
Patients with advanced/metastatic cancer, with measurable disease as determined by RECIST version 1.1, who have progressed despite standard therapy or are intolerant to standard therapy, and for whom no effective therapy is available. Patients must fit into one of the following groups:
Disease that has progressed on standard therapy or for whom there is no other therapy option available
Patients without a curative therapy or whose tumor does not have standard chemotherapy
Patients with advanced melanoma, endometrial carcinoma, pancreatic or TNBC, with measurable or non-measurable disease who have progressed despite standard therapy or are intolerant of standard therapy, or for whom no standard therapy exists.
Dose escalation phase only: Subject not responding to standard therapy or for whom no standard treatment exists
Dose expansion phase: Subject not responding to standard therapy or for whom no standard treatment exists with:
Histopathologically confirmed diagnosis of an advanced solid tumor such as breast cancer or midline carcinoma with NUT rearrangement, that has progressed despite standard therapy, or for which no standard therapy exists. For enrollment in the expansion cohorts, histopathological confirmation of triple-negative breast cancer or high-grade serous ovarian cancer is required.
have metastatic or unresectable advanced solid tumors that have recurred or progressed following standard therapy or
Participants must have received, and then progressed, relapsed, or been intolerant to, at least 1 standard treatment regimen in the advanced or metastatic setting according to solid tumor histologies
Participants must have received, and then progressed, relapsed, or been intolerant to, all standard treatment regimens with proven survival benefit in the advanced or metastatic setting according to tumor type, if such a therapy exists
Patients must have histologically confirmed metastatic or unresectable malignancy that is refractory to standard therapy or for which no standard therapy exists and where irinotecan is deemed a reasonable treatment option
Dose expansion groups of FAZ053 single agent and FAZ053 in combination with PDR001: Patients with advanced/metastatic solid tumors with at least one measurable lesion as determined by RECIST version 1.1 who may or may not have received prior treatment with an immune checkpoint inhibitor (for FAZ053 single agent no treatment with an anti-PD-L1 inhibitor is permitted), who have progressed despite standard therapy, or for whom no standard therapy is available and fit into one of the following groups:
Must have progressed following standard therapy, or for whom, in the opinion of the Investigator, no effective standard therapy exists, is tolerated or appropriate.
All patients participating in this clinical trial must have progressed following standard therapy, or for whom, in the opinion of the Investigator, no effective standard therapy exists, is tolerated or appropriate.
Patients must have histologically documented solid tumors whose disease has progressed on standard therapy or for which there is no available standard therapy
Phase I: histologically confirmed solid tumors that have progressed on standard therapy known to prolong survival or for which no standard treatment options exist
Diagnosed with a locally advanced or metastatic malignancy that has progressed despite standard therapy, or for which no effective standard therapy exists
Patient must have an advanced (metastatic or recurrent) pathologically proven solid tumor which has not responded to standard therapy or which has progressed following standard therapy for advanced disease and/or for which no standard therapy is known to be effective; patients in expansion cohort A must have accessible tumor for biopsy
Relapsed following or progressed through standard therapy
Have a disease for which no standard effective therapy exists (i.e., a therapy that demonstrates a significant increase in survival)
Patients for whom no standard curative therapy exists
Part A of the study will include patients that have histological confirmation of a solid malignancy (other than HCC) that is refractory to standard therapy or for which no standard of care regimen currently exists.
Subjects must have received prior standard therapy appropriate for their tumor type and stage of disease, or in the opinion of the Investigator, would be unlikely to tolerate or derive clinical benefit from appropriate standard of care therapy.
Subject has received at least one prior standard therapy (or generally accepted upfront therapy if no standard exists) and have no known curative therapy.
Participants must have received, and then progressed or been intolerant to, at least 1 standard treatment regimen
Diagnosis of O-AML that is refractory to or intolerant to standard therapy and is no longer likely to respond to such therapy (at least one line of therapy); or Diagnosis of MDS/CMML that is refractory to or intolerant to standard therapy and is no longer likely to respond to such therapy (at least one line of therapy)
During dose escalation, subjects with advanced solid tumors that have progressed following at least one standard regimen
All patients participating in this clinical trial must have progressed following standard therapy or, in the opinion of the Investigator, no effective standard therapy exists, is tolerated, appropriate or is considered equivalent to study treatment.
If an approved first-line standard therapy for the patient’s tumor is available, subjects must have failed, be intolerant to, be ineligible for, or have refused that treatment; enrollment of patients for whom no standard therapy exists or who decline standard therapy should be discussed with the principal investigator prior to enrollment; patients must have progressive disease on study entry
All patients must have received prior first line standard therapy or declined standard therapy
Patients for whom no standard curable therapy exists
Diagnosis of one of the following: 1. Part 1: Histologically- or cytological-confirmed diagnosis of non-resectable or metastatic solid malignancy. At the time of enrollment, subjects either: have progressed on prior therapy (radiographic documentation of progression is adequate for study participation) AND have no standard-of-care therapy that would be expected to achieve a durable clinical response, OR refuse standard therapy, OR are not candidates for standard therapy, OR have a disease for which no generally-accepted standard-of-care exists. 2. Part 2: Histologically- or cytologically-confirmed diagnosis of metastatic or non-resectable triple-negative breast cancer (TNBC) (estrogen receptor [ER]-/ progesterone receptor [PR]-/Human Epidermal Growth Factor Receptor 2 [Her2]-, as defined by local laboratory standards); metastatic or non-resectable transitional cell carcinoma of the bladder, ureter, or renal pelvis; recurrent GBM; or non-Hodgkin's lymphoma. At the time of enrollment, subjects either: have progressed on prior therapy (radiographic documentation of progression is adequate for study participation) AND have no standard-of-care therapy that would be expected achieve a durable clinical response, OR refuse standard therapy, OR are not candidates for standard therapy.
Patients must have a histologically-confirmed metastatic or locally advanced solid tumor that has failed to respond to standard therapy, progressed despite standard therapy, or for which standard therapy does not exist
Patient has an advanced malignancy that has progressed or recurred following standard therapy for advanced disease, and for which no curative therapies are available.
Histologically or cytologically documented, locally advanced or metastatic solid malignancy that has progressed on available standard systemic therapy, and for whom no effective therapy or standard of care exists.
Have refused standard therapy
Progressed, or been intolerant to, at least one standard treatment regimen, except for subjects in 1st line cohorts.
PHASE I COMPONENT: Histologic confirmation of relapsed/refractory solid tumors, including tumors of the central nervous system that have failed to respond to standard therapy, progressed despite standard therapy, or for which standard therapy does not exist; patients with diffuse pontine glioma are not required to have histologic confirmation of disease, and are eligible with radiologic confirmation
Failure to respond to or refractory to approved/standard therapy; or for whom standard therapy does not exist, or is not tolerable; or for whom approved/standard therapy is not considered to be sufficient or appropriate by the Investigator.
PROCUREMENT: Cancer is:\r\n* Recurrent or persistent after standard therapy OR\r\n* Patient is unable to receive standard therapy
TREATMENT: Cancer is:\r\n* Recurrent or persistent after standard therapy OR\r\n* Patient is unable to receive standard therapy
Patients with a recurrent/metastatic or refractory solid tumor that has progressed or did not respond to standard therapy, or for which no standard anticancer therapy exists or is too toxic
For initial VSTs and subsequent infusions: patients will be eligible following any type of allogeneic transplant if they have CMV, adenovirus, EBV, BK virus and/or HHV6 infection/disease persistent or recurrent despite 14 days of standard therapy OR after failure of treatment after 7 days of standard therapy OR if unable to tolerate standard therapy; patients with persistent human polymavirus type II (JC) virus infection will be eligible as well
Have histologic or cytological proof of advanced cancer that has progressed and for which there is no further standard anticancer therapy available in the opinion of the investigator.
Failure to respond to standard therapy (usually combination chemotherapy with or without radiation and surgery) or development of progressive disease at any phase of standard therapy (any new lesion or an increase in size > 25% of a pre-existing lesion); patients may enter this study with or without re-induction therapy for recurrent tumor
Additional inclusion for part A: Has a histological confirmation of a solid malignancy (other than HCC) that is refractory to standard therapy or for which no standard of care regimen currently exists.
Patients will undergo standard pre-transplant work-up as dictated by standard practice guidelines the results of which may be used for screening for this study
Stage IIB-IV mycosis fungoides or Sezary syndrome, who have failed at least 1 standard systemic therapy or are not candidates for standard therapy
Disease that has progressed after standard therapies or for which standard therapy is otherwise unsuitable (example, intolerance).
Patients who refuse standard therapy are excluded from the study
Dose escalation: Patients with accessible tumors and with measurable disease as determined by RECIST 1.1 who have received at least one but no more than three prior lines of treatment for their disease and progressed despite standard treatment or are intolerant of standard treatment, or for whom no standard treatment exists
Dose expansion: Patients with advanced/metastatic solid tumors: head and neck squamous cell carcinoma (HNSCC), melanoma, accessible tumors and visceral tumors (LHC165 combination with PDR001 only). Patients must have measurable disease as determined by RECIST 1.1, and have progressed despite standard treatment or are intolerant to standard treatment, or for whom no standard treatment exists and have received at least one but no more than three prior lines of treatment for their disease.
Patients with confirmed diagnosis of advanced malignancy, whose disease failed to respond to or progressed after standard therapy; they could not tolerate standard therapy; or such measures are not acceptable to the subject.
Patients with histologically or cytologically confirmed, advanced solid tumors which have progressed despite standard therapy or for whom no standard therapy exists.
Must have received or been intolerant to standard therapy.
Patients must have histologically confirmed solid tumors that have progressed on standard therapy known to prolong survival or for which no standard treatment options exist
Patients must have histologically confirmed solid tumors that have progressed on standard therapy known to prolong survival or for which no standard treatment options exist
Patient must have non-resectable disease that has progressed following standard therapy or has not adequately responded to standard therapy, or the patient must be intolerant to or have declined available standard therapies, or there must be no accepted standard therapy for their disease.
TUMOR BIOPSY SEQUENCING: Patients with histologically documented solid tumors whose disease has progressed following at least one line of standard therapy and/or no standard of treatment exists that has been shown to prolong survival
TREATMENT: Patients with histologically documented solid tumors whose disease has progressed following at least one line of standard therapy or for which no standard therapy exists that has been shown to prolong survival
Subjects must be diagnosed with a glioma, cholangiocarcinoma or other solid malignant tumor that has progressed despite standard therapy, or for which no effective standard therapy exists, with biopsy-confirmed evidence of an IDH1 or IDH2 mutation associated with neomorphic activity of the encoded proteins
Advanced or metastatic cancer for which no standard therapy exists or that has\n             progressed despite standard therapy
DOSE ESCALATION PHASE: Histological or cytopathological diagnosis of an advanced cancer that is refractory to standard therapy or for which no standard therapy exists
Patients with histologically or cytologically proven advanced solid cancer and have undergone treatment with at least one regimen of standard therapy, either cytotoxic chemotherapy, a molecularly targeted agent, or immunotherapy, or have a form of cancer for which no standard therapy exists; patients with prostate cancer may continue on androgen-deprivation therapy if they are currently receiving it
Locally recurrent or metastatic disease that has progressed on or following standard treatment, or is not a candidate for standard treatment
During dose escalation, subjects with advanced solid tumors (except for primary CNS metastases) that have progressed following at least one standard regimen
Histologically or cytologically proven metastatic or locally advanced tumors for which no standard therapy exists, or where standard therapy has failed, or in patients otherwise ineligible for standard therapy, or for an indication that anti-programmed cell death protein 1 (PD-1) therapy has been shown to be effective in studies in HIV-uninfected participants; disease-specific criteria will be applied for certain common cancers and cancers strongly associated with HIV; however, enrollment will not be confined to these tumors
Subjects must have received and have progressed, or are refractory to standard regimens
Phase I only: any (or no) prior therapy for metastatic disease is allowed, including cetuximab; if a patient has not received prior standard therapy, s/he must have been offered and refused prior standard therapy
Subjects who have progressed or have been intolerant to any standard treatment regimen or refused standard treatment, or for which adequate standard therapy does not exist.
Patient must have received at least 1 prior standard therapy for their disease
Subjects who have progressed on (or not been able to tolerate) standard anticancer therapy or for whom no standard anticancer therapy exists. Must have disease that is objectively measurable
Group 2: BRAFV600 positive metastatic colorectal carcinoma (CRC), or advanced non-small cell lung carcinoma (NSCLC) after failure of at least two lines of prior standard therapy or for whom no further standard therapy is indicated.
Histologically or cytologically confirmed advanced solid tumors (excluding HCC) that have progressed following standard therapy, or for which no standard therapy exists (including surgery or radiation therapy) or participants with RR-DTC.
Refractory to or intolerant of standard therapy
Standard treatment interrupted, except if anti-HER2 therapy
Has stable, or no evidence of, extracranial disease and not receiving systemic therapy for extracranial disease; Note: patients with stable disease must have already received standard therapy or are intolerant to standard therapy
Patients with advanced/metastatic cancer, with measurable disease as determined by RECIST version 1.1, who have progressed despite standard therapy or are intolerant to SOC, or for whom no standard therapy exists. Patients must fit into one of the following groups: • CRC •NSCLC • TNBC• RCC
Has progressed after prior therapy and there is no further effective standard anticancer therapy available (including subject refuses or is intolerant)
Participants must have relapsed disease despite standard therapy
Diagnosis of advanced or recurrent, histologically or cytologically confirmed, solid malignancy that is either metastatic or unresectable. At time of enrollment, subjects either refuse standard curative or palliative therapy, are not candidates for standard curative or palliative therapy, have a disease for which no non-investigational therapy exists, OR have progressed on prior therapy (up to three lines of prior cytotoxic agents are permitted).
Patients must have received standard therapy (or generally accepted upfront therapy if no standard exists) and have no known curative therapy
Have histological or cytological diagnosis of locally advanced/metastatic HER2 solid tumors that has progressed or become intolerant to standard therapy or for which no standard therapy is available
Patient with histologically-confirmed Stage IV malignant metastatic adenocarcinoma of the pancreas; (a) who has relapsed from or is refractory to standard therapy and for whom no therapy exists that would be curative or might provide significant benefit or (b) who are intolerant to or refuse standard chemotherapy and, therefore, for whom experimental therapy is a reasonable option.
Must have received and have progressed, are refractory, or are intolerant to standard therapy appropriate for the specific tumor type. Subjects should not have received more than 5 prior lines of therapy for recurrent or metastatic disease including both standards of care and investigational therapies
Subjects must have histologically or cytologically confirmed, IDH1 gene-mutated advanced solid tumors, including glioma, that have recurred or progressed following standard therapy, or that have not responded to standard therapy.
Patient has a confirmed solid tumor diagnosis according to the following: a. Phase 1: patient has a recurrent or refractory solid tumor that has progressed or did not respond to standard therapy, or for which no standard anticancer therapy exists b. Phase 2: patient has radiologically documented measurable disease by RECIST 1.1 (for neuroblastoma, evaluable disease by MIBG/Curie score is also acceptable) in one of the following tumor types and has failed up to three lines of treatment i. Group 1: neuroblastoma ii. Group 2: rhabdomyosarcoma iii. Group 3: Ewing's sarcoma Phase 1 portion or in preclinical studies
Part A1 only: Patients with histological or cytological diagnosis of HNSCC, HCC, melanoma, or clear cell RCC who progressed on or are intolerant to standard therapy, for which no standard therapy is available or who decline standard therapy.
Patients must have histologically documented solid tumors whose disease has progressed on standard therapy that is known to be associated with a survival advantage or have disease for which there is no known standard therapy
Patient has advanced solid malignancy that has progressed despite standard therapy, or for which no effective standard therapy exists
Failure to respond to standard therapy, or for whom standard therapy does not exist.
The participant has a histologic or cytologic diagnosis of a solid tumor (non-prostate, non-breast) that is metastatic and is refractory to or progressed (or relapsed) following standard therapies, or has disease for which no standard therapy exists; presence of metastatic bone lesion(s) is required
Progressed or not tolerated standard therapy, and no further standard therapy is available
Show objective disease progression after the last administration of the last standard therapy or have stopped standard therapy due to intolerability (excluding ASPS subjects who have not received prior therapy) within 6 months of enrollment.
Patients must have a histologically-confirmed metastatic or locally advanced cancer that has failed to respond to standard therapy, progressed despite standard therapy, or for which standard therapy that increases survival by at least three months does not exist
In investigators opinion, no curative standard therapy exists
Histological or cytological diagnosis of advanced/metastatic solid tumor malignancy. Dose Finding Cohorts: Tumor types will be limited to CRC, SCCHN, squamous NSCLC, bladder, or ovarian carcinomas which have progressed on standard therapy, or for which no standard therapy is available.
Part 1: Subjects with solid tumors that are refractory to, relapsed after or intolerant to standard therapy, or for whom no standard therapy exists or who are considered by the investigator to be inappropriate for standard therapy.
Tumor progression following at least one prior standard therapy
Patients for whom no standard curable therapy exists
Advanced or metastatic solid tumor that has progressed or was not responsive to standard therapy
Phase I: Patients with advanced/metastatic solid tumors, with measurable or non-measurable disease as determined by modified RECIST version 1.1 who have progressed despite standard therapy or be intolerant of standard therapy, or for whom no standard therapy exists, who have tumors harboring one of the following: confirmed PIK3CA mutation or amplification, PTEN loss of function, EGFR mutation, cMET activation and/or HER2 overexpression. Endometrial carcinoma will not be selected for any molecular status.
Phase II: Patients with advanced/metastatic solid tumors, with at least one measurable lesion as determined by modified RECIST version 1.1, who progressed despite standard therapy or be intolerant of standard therapy, or for whom no standard therapy exists, fitting in one of the following groups: Group 1: patients with PIK3CA mutated or amplified ER positive (ER+) breast cancer ; Group 2: patients with endometrial carcinoma (not selected for any molecular status); Group 3: patients with solid tumors (with the exception of PIK3CA mutant/amplified ER+ breast cancer and endometrial carcinoma) harboring PIK3CA mutation or amplification/any PTEN status; Group 4: patients with solid tumors (with the exception of endometrial carcinoma) harboring PTEN loss of function/ PIK3CA wild type; Group 5: non-small cell lung cancer harboring cMET activation and/or EGFR mutation. Up to 3 lines of chemotherapy allowed in advanced/metastatic setting.
Patients with locally advanced or metastatic solid tumors who have either relapsed following, or progressed through, standard therapy; have a current disease state for which there is no standard effective therapy; is not a candidate for, or is unwilling to undergo, standard therapy in cases where no curative option exists.
Advanced malignancy, metastatic or unresectable, that has recurred or progressed following standard therapy or failed standard therapy; or for which no standard therapy currently exists, or for which subject is not a candidate for, or is unwilling to undergo, standard therapy.
Pathologically confirmed advanced G/GEJ/E adenocarcinoma (Cohort 1) or other solid tumor (Cohort 2) for which subject has received prior therapy for advanced disease, for which no standard therapy exists, or subject refuses standard therapy
Patients must have either progressed on least one standard therapy or there must be no standard treatment exists that has been shown to prolong survival for the patient’s disease; patients may have received any number of prior cytotoxic agents
Subjects must have confirmed advanced solid tumor and have progressed, are refractory, or are intolerant to standard therapy appropriate for tumor type. Subjects should not have received more than 3 prior lines of therapy for recurrent or metastatic disease including both standards of care and investigational therapies.
Diagnosis of teratoma for which no additional standard surgical or medical therapy exists
progressed or recurred despite standard therapy
no standard therapy exists
patient is intolerant of standard therapy
At least two-weeks since receipt of prior standard or investigational therapy
Patients must have histologically or cytologically confirmed solid malignancy that is metastatic or unresectable, for which standard curative measures do not exist, that has progressed on at least one line of standard therapy or for which no standard therapies exists
All patients must have received prior first line standard therapy or declined standard therapy, and have been either non-responders (progressive disease) or have recurred
Histologically or cytologically confirmed advanced solid tumor, including glioma, or angioimmunoblastic T-cell lymphoma (AITL) that has recurred or progressed following standard therapy, or that has not responded to standard therapy
Histological or cytological diagnosis of advanced/metastatic solid tumor malignancy which has progressed on standard therapy or for which no standard therapy is available.
Histologically- or cytologically-confirmed melanoma or clear-cell RCC that are refractory to standard therapy or for which no standard therapy exists
Histologically or cytologically confirmed gastrointestinal (GI) carcinoma, which has progressed on standard therapies (surgery, radiotherapy, endocrine therapy, chemotherapy), for which effective therapy is not available or for which patients are not a candidate for or intolerant of such therapies.
Patients must have histologic or cytologic evidence of a solid neoplasm for which no standard therapy is available, or have progressed despite standard therapy, or are intolerant to standard therapy.
Progressed or refractory to at least 1 prior line of standard therapy
Patients with cytopathologically or histopathologically confirmed diagnosis of an advanced solid tumor which has progressed despite standard therapy, or for which no standard therapy exists or patients with locally advanced or metastatic basal cell carcinoma who are not amendable or eligible for standard therapy.
Advanced malignant solid tumors for which no curative therapy exists that has recurred or pgrogressed following standard therapy
Progressed, or been intolerant to, at least one standard treatment regimen
Tumors that are relapsed or refractory to at least 1 prior anti-cancer systemic therapy and for which no standard therapy exists
Patients must have histologically or cytologically confirmed advanced malignant solid tumor that has recurred or progressed following standard therapy, or that has not responded to standard therapy, or for which there is no standard therapy, or who are not candidates for standard therapy
RCC patients only: Tumor progression after receiving standard/approved chemotherapy and/or targeted agent, where there is no approved therapy or for tumors where sorafenib based therapy would be standard therapy (Phase I)
Diagnosed with a locally advanced or metastatic malignancy that has progressed despite standard therapy, or for which no effective standard therapy exists. Only patients with tumors characterized by genetic abnormalities in ALK were enrolled.
Diagnosed with advanced refractory solid malignancies or intolerant of standard therapy for the stage of the disease (because there is currently no standard approved therapy for adenoid cystic carcinoma, therefore there is no requirement of prior therapy for this patient population)
Dose-escalation stage: Participants with histologically documented incurable, locally advanced, or metastatic epithelial malignancy that has progressed despite standard therapy or for which no standard therapy exists
Expansion stage: Participants with one of the following epithelial, histologically-documented, incurable, locally advanced, or metastatic tumor that has progressed despite standard therapy or for which no standard therapy exists: CRC, NSCLC, HNSCC, or pancreatic cancer
Disease that has progressed after standard therapy for the specific tumor type, or for which standard therapy has proven to be ineffective, intolerable, or is considered inappropriate, or if no further standard therapy exists; exceptions: NSCLC, head and neck squamous cell cancer (HNSCC), bladder cancer, MSI-H/dMMR cancers and melanoma expansion cohorts in Part 2B pembrolizumab combination. 1) Subjects must not have received more than 5 prior lines of therapy for advanced disease including both standards of care and investigational therapies. 2) Subjects who received prior anti-Programmed cell death protein 1(PD-1)/ Ligand-1 (L1) therapy must have received at least 4 months of treatment (Part 1B and Part 2B).
Phase I-Ib part (including dose ranging part): Patients with advanced/metastatic solid tumors, with measurable or non-measurable disease as determined by RECIST v1.1, who have progressed despite standard therapy or are intolerant of standard therapy, or for whom no standard therapy exists and who did not receive prior anti-PD-1/PD-L1 treatment.
Phase II part (MBG453 single agent): Patients with advanced/metastatic solid tumors in the indication in which at least one confirmed PR or CR was seen during the dose escalation phase I part. Patients must have measurable disease as determined by RECIST v1.1, have progressed despite standard therapy or be intolerant to standard therapy.
Phase II part (MBG453 in combination PDR001): Patients with advanced/metastatic tumors in the below selected indications, with at least one measurable lesion as determined by RECIST v1.1, who have received standard therapy and are intolerant of standard therapy or have progressed following their last prior therapy.:
Has progressed after prior therapy and either a) there is no further effective standard anticancer therapy available (including subject refusal) or b) is intolerant to standard anticancer therapy.
Histologically confirmed advanced malignancy defined as any of the following tumors for which no further standard or curative therapy exists or is considered appropriate by the Investigator:
Participants with hepatocellular carcinoma or Intrahepatic Cholangiocarcinoma (ICC) who have progressed despite standard therapy or are intolerant of standard therapy
Confirmed locally advanced and/or metastatic solid tumor in participants who have progressed on a standard therapy, are intolerant to standard therapy, and/or are non-amenable to standard therapy
Patients with a histologically/cytologically confirmed diagnosis of advanced disease of any of the following tumors that progressed to standard therapy or for whom no standard therapy exists:
Must have received and progressed on or failed one standard/approved treatment for cancer type, if available