Prior exposure to immune-mediated therapy, including durvalumab and tremelimumab, except for anti-PD-1 or anti-PD-L1 therapy (including durvalumab) in NSCLC patients; this includes anti-CTLA-4 agents (prior treatment with these agents is NOT allowed in either cohort) and, excludes therapeutic anticancer vaccines, excluding therapeutic anticancer vaccines; exposure to other investigational agents may be permitted after discussion with the study principal investigator (PI)
Patients may have received prior anti-CTLA4 or other anti-PD-1/anti-PD-L1 therapy, not both, provided that it is completed >= 4 weeks prior to registration
Patients must not have had prior immunotherapy with anti-PD-L1, anti-PD-1, anti-CTLA4 or similar drugs; patients must not be planning to receive any of the prohibited therapies during the screening or treatment phases of the study
Prior IL-15 treatment or cytotoxic therapy, immunotherapy, radiotherapy, major surgery, antitumor vaccines or monoclonal antibodies in the 4 weeks prior or for checkpoint inhibitors such as anti-CTLA-4 or anti PD1/PD-L1 or nitrosoureas or mitomycin C for 6 weeks prior to C1D1.
6. Part A: Prior exposure to immunotherapy such as but not limited to other anti-CTLA-4, anti-PD-1, or anti-PD-L1 antibodies excluding vaccines. Part B: Exclusion of prior immunotherapy exposure will be limited to anti-PD-1, anti-PD-L1, or anti-PD-L2;
Prior treatment with cluster of differentiation 137 (CD137) agonist or immune checkpoint blockade therapies, anti-programmed-death-1 (anti-PD-1), and anti-PD-L1 therapeutic antibody
Has received pembrolizumab, or prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody as part of any previous therapy, including trials
Subjects previously treated with T cell immune-modulating antibodies, including anti-CTLA-4, anti-PD-1 and/or anti-PD-L1 agents
Patient with melanoma, ovarian cancer, renal cell carcinoma, colorectal cancer, and other solid tumors who have received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PDL2 antibody; melanoma patients who received anti-PD-1 antibodies in the adjuvant setting are allowed to participate as long as their last anti-PD-1 antibody was given at least 6 months prior to their planned start of study therapy
Patients should be excluded if they have had prior systemic treatment with an anti-CTLA4 antibody and anti-PD1/PDL1 antibody; prior treatment with single agent anti-CTLA4, anti-PD1 or anti-PDL1 antibody is allowed
Subject on prior chemotherapeutic, immunomodulator (such as anti-CTLA-4, anti-PD-1 or anti-PD-L1 inhibitor), investigational, or other therapies for the treatment of cancer must wait at least 28 days after the last dose of these therapies before administration of the first dose of the IMP.
Prior treatment with PV-10 or any anti-PD-1 antibody
Prior therapy with any anti-PD-1, anti-PD-L1, L2, anti-4-1BB (CD137), or anti-CTLA 4 therapy.
Prior treatment with CD137 agonists or immune checkpoint-blockade therapies, including anti-CD40, anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies.
Prior treatment with T-cell co-stimulating or immune checkpoint blockade therapies, including anti?CTLA-4, anti?PD-1, and anti?PD-L1 therapeutic antibodies
Prior treatment with cluster of differentiation 137 (CD137) agonists or immune checkpoint-blockade therapies, including anti-cluster of differentiation 40 (anti-CD40), anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4), anti-programmed death-1 (anti-PD-1), and anti-PD-L1 therapeutic antibodies
Received prior therapy with an anti-PD-1, anti-PD-L1, or anti-CTLA-4 antibody
For Cohort Expansion, patients who have previously received an immune checkpoint inhibitor (e.g., anti-PD-L1, anti-PD-1, anti-CTLA-4) are not eligible for this study.
Prior treatment with cluster of differentiation 137 (CD137) agonists or immune checkpoint blockade therapies, including anti-CD40, anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4), anti-programmed death-1 (anti-PD-1), and anti-PD-L1 therapeutic antibodies
INCLUSION CRITERIA - For Parts 1-4:\n\n          -  Willing and able to provide written informed consent\n\n          -  Histologically confirmed diagnosis of a locally advanced (not amenable to curative\n             therapy such as surgical resection) or metastatic melanoma, RCC, NSCLC, urothelial\n             carcinoma, or TNBC\n\n          -  Male or female patients, age 18 years or older at the time of signing the informed\n             consent form (ICF)\n\n          -  Life expectancy > 12 weeks\n\n          -  Patients must not have received prior interleukin-2 (IL-2) therapy\n\n          -  Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1\n\n          -  Measurable disease per RECIST 1.1\n\n          -  Demonstrated adequate organ function within 14 days of treatment initiation\n\n          -  Oxygen saturation ? 92% on room air.\n\n          -  Subjects must be recovered from the effects of any prior chemotherapy, immunotherapy,\n             other prior system anticancer therapy, radiotherapy, or surgery. Clinically\n             significant toxic effect(s) of the most recent prior chemotherapy must be resolved to\n             Grade 1 or less (except alopecia and sensory neuropathy).\n\n          -  Women of childbearing potential must agree to use highly effective methods of birth\n             control. All participants must agree to use double barrier contraception during study\n             participation for at least 6 months after the last dose of study drugs.\n\n          -  Patients with stable brain metastases may be enrolled if certain criteria are met.\n\n          -  Fresh and archival tumor tissue available\n\n          -  Additional criteria may apply.\n\n        INCLUSION CRITERIA - For Part 2:\n\n          -  MELANOMA:\n\n               -  Histologically confirmed stage III (unresectable) or stage IV melanoma, as per\n                  American Joint Committee on Cancer (AJCC) staging system\n\n               -  Ocular melanoma will be excluded\n\n          -  Melanoma Subpopulation A 1st-line (1L):\n\n               -  Have not received prior anti-cancer therapy for advanced or metastatic melanoma\n\n               -  Known BRAF status, or consent to testing, as per regionally acceptable V600\n                  mutational status testing\n\n          -  Melanoma Subpopulation B (2nd- and 3rd-line (2-3L), anti-PD-1 or anti-PD-L1 therapy\n             relapsed/refractory):\n\n               -  2-3L, patients must have confirmed radiographic disease progression no earlier\n                  than 4 weeks after initial disease progression but within 3 months from last dose\n                  of anti-PD-1 or anti PD-L1 containing regimen. Patients must consent to providing\n                  pre-study scans (if available) to confirm radiographic progression.\n\n               -  Patients may have received no more than 1 prior anti-angiogenic therapy or\n                  cytotoxic chemotherapy regimen.\n\n          -  RENAL CELL CARCINOMA (RCC):\n\n               -  Advanced (not amenable to curative surgery or radiation therapy) or metastatic\n                  (AJCC stage IV) RCC\n\n               -  Histologically confirmed RCC with a clear-cell component.\n\n          -  RCC Subpopulation A (1L):\n\n               -  1L, patients may have not received prior anti-cancer therapy for advanced or\n                  metastatic RCC.\n\n          -  RCC Subpopulation B (2-3L, anti-PD-1 or anti-PD-L1 relapsed/refractory):\n\n               -  2-3L, patients must have confirmed radiographic disease progression no earlier\n                  than 4 weeks after initial disease progression but within 3 months from last dose\n                  of anti-PD-1 or anti-PD-L1 containing regimen. Patients must consent to providing\n                  pre-study scans (if available) to confirm radiographic.\n\n               -  Patients may have received no more than 1 prior anti-angiogenic therapy or\n                  cytotoxic chemotherapy regimen.\n\n          -  NON-SMALL CELL LUNG CANCER (NSCLC):\n\n               -  Histologically confirmed or cytologically confirmed diagnosis of stage IV NSCLC\n\n                    -  Patients with nonsquamous NSCLC must lack epidermal growth factor receptor\n                       (EGFR)-sensitizing mutation and/or anaplastic lymphoma kinase (ALK)\n                       translocation\n\n          -  NSCLC Subpopulation A (1L):\n\n               -  1L, patients must not have received prior anti-cancer therapy for advanced or\n                  metastatic NSCLC. Patients must have known PD-L1 status as per validated\n                  immunohistochemistry testing. Up to 20 patients will be enrolled in each\n                  subgroup:\n\n                    -  PD-L1 negative (PD-L1 < 1%),\n\n                    -  PD-L1 positive (PD-L1 ? 50%),\n\n                    -  PD-L1 low/intermediate (PD-L1 ? 1% - < 50%).\n\n               -  For patients who do not have known PD-L1 status, testing must be done using an\n                  FDA-approved PD-L1 test.\n\n          -  NSCLC Subpopulation B (2L, I-O therapy naïve):\n\n               -  2L, patients must have experienced disease recurrence or progression during or\n                  after one prior platinum doublet-based chemotherapy regimen for advanced or\n                  metastatic disease. Patients who received platinum-containing adjuvant,\n                  neoadjuvant, or definitive chemoradiation therapy given for locally advanced\n                  disease and developed recurrent (local or metastatic) disease within 6 months of\n                  completing therapy are eligible. Patients must not have received any prior\n                  immune-oncology regimens, including but not limited to checkpoint inhibitors such\n                  as anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody, or any\n                  other antibody or drug specifically targeting T cell co-stimulation or checkpoint\n                  pathways, indoleamine 2,3 dioxygenase pathway inhibitors, cancer vaccines,\n                  adoptive cell therapies, or other cytokine therapies.\n\n          -  NSCLC Subpopulation C (2-3L, anti-PD-1 or anti-PD-L1 relapsed/refactory):\n\n               -  2-3L, patients must have confirmed radiographic disease progression no earlier\n                  than 4 weeks after initial disease progression but within 3 months from last dose\n                  of anti-PD-1 or anti-PD-L1 containing regimen. Patients must consent to providing\n                  pre-study scans (if available) to confirm radiographic.\n\n          -  UROTHELIAL CARCINOMA (UC)\n\n               -  Histologically or cytologically documented locally advanced or transitional cell\n                  carcinoma of the urothelium including renal pelvis, ureters, urinary bladder, or\n                  urethra. Patients with mixed histologies are required to have a dominant\n                  transitional cell pattern.\n\n               -  For patients who received prior adjuvant/neoadjuvant chemotherapy or\n                  chemo-radiation for urothelial carcinoma, a treatment-free interval of more than\n                  12 months between the last treatment administration and the date of recurrence is\n                  required to be considered treatment naive in the metastatic setting.\n\n          -  UC Subpopulation A (1L)\n\n               -  Enrollment of urothelial carcinoma 1L patients will target accrual of up to 20\n                  patients who are cis-ineligible and up to 20 patients, who after consultation\n                  with the Investigator, choose to forego front-line chemotherapy\n\n               -  Treatment naive and cisplatin-eligible patients who refuse standard of care.\n\n          -  UC Subpopulation B (1L) cisplatin-ineligible\n\n               -  Treatment naive and cisplatin-ineligible patients who meet at least one of the\n                  following criteria:\n\n                    -  Creatinine clearance (calculated or measured) < 60 mL/min\n\n                    -  Common Terminology Criteria for Adverse Events (CTCAE) v4.03 Grade ? 2\n                       audiometric hearing loss\n\n                    -  CTCAE v4.03 Grade ? 2 peripheral neuropathy\n\n                    -  New York Heart Association (NYHA) Class III heart failure\n\n               -  No prior chemotherapy for inoperable locally advanced or metastatic urothelial\n                  carcinoma. Prior local intravesical chemotherapy is allowed if completed at least\n                  4 weeks prior to the initiation of study treatment.\n\n               -  Patients must not have received any prior immune-oncology regimens, including but\n                  not limited to checkpoint inhibitors such as anti-PD-1, anti-PD-L1, anti-PD-L2,\n                  anti-CD137, or anti-CTLA-4 antibody, or any other antibody or drug specifically\n                  targeting T cell co-stimulation or checkpoint pathways, indoleamine\n                  2,3-dioxygenase pathway inhibitors, cancer vaccines, adoptive cell therapies, or\n                  other cytokine therapies.\n\n          -  UC Subpopulation C (3L, anti-PD-1 or anti-PD-L1 relapse/refractory)\n\n               -  Patients must have progressed on only one prior line of therapy that contains\n                  platinum-based chemotherapy in the metastatic setting or post platinum-based\n                  chemotherapy in an adjuvant setting with progression < 6 months.\n\n               -  Patients must have received only one prior line of therapy with an anti-PD-1 or\n                  anti-PD-L1 containing regimen, which must be their most recent anti-cancer\n                  treatment.\n\n               -  Patients must have confirmed radiographic disease progression no earlier than 4\n                  weeks after initial disease progression but within 3 months from last dose of\n                  anti-PD-1 or anti-PD-L1 containing regimen. Patients must consent to providing\n                  pre-study scans (if available) to confirm radiographic.\n\n          -  TRIPLE-NEGATIVE BREAST CANCER (1-2L, I-O therapy naïve)\n\n               -  Less than 1% of tumor cell nuclei test positive for estrogen and progesterone\n                  receptors determined by using standard immunohistochemistry (IHC)\n\n               -  Human epidermal growth factor 2 (HER2) negative as determined by local\n                  pathologist, using IHC or in situ hybridization\n\n               -  Patients may have received only 1 prior line of therapy with chemotherapy,\n                  adjuvant setting excluded, or patient refuses standard of care.\n\n               -  Must not have received any prior immune-oncology regimens, including but not\n                  limited to checkpoint inhibitors such as anti-PD-1, anti-PD-L1, anti-PD-L2,\n                  anti-CD137, or anti-CTLA-4 antibody, or any other antibody or drug specifically\n                  targeting T cell co-stimulation or checkpoint pathways, indoleamine 2,\n                  3-dioxygenase pathway inhibitors, cancer vaccines, adoptive cell therapies, or\n                  other cytokine therapies.\n\n        INCLUSION CRITERIA - For Parts 3 and 4:\n\n          -  RENAL CELL CARCINOMA (1L):\n\n               -  Advanced (not amenable to curative surgery or radiation therapy) or metastatic\n                  (AJCC stage IV) RCC.\n\n               -  Histologically confirmed RCC with a clear-cell component.\n\n               -  Patients must not have received prior anti-cancer therapy for advanced or\n                  metastatic RCC\n\n          -  NON-SMALL CELL LUNG CANCER (1L):\n\n               -  Histologically confirmed or cytologically confirmed diagnosis of stage IV NSCLC\n\n               -  Patients with nonsquamous NSCLC must lack epidermal growth factor receptor\n                  (EGFR)-sensitizing mutation and/or anaplastic lymphoma kinase (ALK)\n                  translocation.\n\n               -  Patients must not have received prior anti-cancer therapy for advanced or\n                  metastatic NSCLC.\n\n        EXCLUSION CRITERIA - For Parts 1-4:\n\n          -  Use of an investigational agent or an investigational device within 28 days before\n             administration of first dose of NKTR--214\n\n          -  Females who are pregnant or breastfeeding\n\n          -  Participants who have an active autoimmune disease requiring systemic treatment within\n             the past 3 months or have a documented history of clinically severe autoimmune disease\n             that requires systemic steroids or immunosuppressive agents\n\n          -  History of organ transplant that requires use of immune suppressive agents\n\n          -  History of allergy or hypersensitivity to study drug components\n\n          -  Active malignancy not related to the current diagnosed malignancy\n\n          -  Evidence of clinically significant interstitial lung disease or active, noninfectious\n             pneumonitis\n\n          -  Prior surgery or radiotherapy within 14 days of therapy\n\n          -  Participants who have had < 28 days since the last chemotherapy, biological therapy,\n             or < 14 days from approved tyrosine kinase inhibitor (TKI) therapy (sunitinib,\n             sorafenib, vemurafenib, dabrafenib, cobimetinib, erlotinib, gefitinib, afatinib,\n             osimertinib), or systemic or inhaled steroid therapy at doses greater than 10mg of\n             prednisone or equivalent before administration of the first dose of study medication\n\n          -  Participant's inability to adhere to or tolerate protocol or study procedures\n\n          -  Additional criteria may apply.
Previous therapy with histone deacetylase (HDAC) inhibitor and/or anti PD 1, anti PD L1, or anti CTLA4 immunotherapy.
Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti CTLA-4, anti-PD1 and anti-PD-L1 therapeutic antibodies
Last dose of prior immunotherapies including but not limited to: interferon alpha, interferon-beta, interleukin (IL)-2, conjugated IL-2, cergutuzumab amunaleukin (CEA-IL2v) , cytokines, anti-cytotoxic T lymphocyte antigen-4, anti-PD-L1, or anti-PD-1 <28 days prior to first cergutuzumab amunaleukin infusion
Patients must not have had prior immunotherapy with anti-PD-L1, anti-PD-1, anti-CTLA4 or similar drugs.
Have received an anti-PD1 or anti PDL1 monoclonal antibody
Previous systemic exposure to anti-CTLA-4 antibody or anti-PD1 antibody
Refractory patients who are naïve to anti-PD-1/PDL-1 therapy OR Relapsed after 3 or more lines of therapies; and are naïve to anti-PD-1/PDL-1 therapy OR
Participants may have had prior immuno-oncology (IO) therapy (including but not limited to anti-CTLA4 and anti-PD1/L1) excluding prior CSF1R directed agents for the study arm containing cabiralizumab
Patients must have prior exposure to an anti-PD1 or anti-PDL1 mAb, if eligible for immunotherapy in the judgment of the local investigator
Prior exposure to investigational immunotherapies, including anti-CTLA4, anti-OX40, anti-CD40, anti-CD27, anti-TNFR antibodies or other investigational immunotherapies, is acceptable
Has received prior therapy with an anti-CTLA-4, anti-PD-1, anti-PD-L1, or anti-PDL2 agent
Immune-checkpoint inhibitors (e.g., anti-PD-1, anti-PD-L1, or anti-CTLA-4), monoclonal antibodies, antibody-drug conjugates, radioimmunoconjugates, or T-cell or other cell-based therapies: 4 weeks (2 weeks with documented disease progression).
ARM I INCLUSION CRITERIA: Subjects are currently on checkpoint inhibitor (anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody, or antibodies to tumor necrosis factor family including OX40) or tumor vaccine for systemic disease who develop new brain metastases, must have documented stable systemic disease within 30 days of signing consent
ARM I INCLUSION CRITERIA: Subjects who have completed prior checkpoint inhibitor (anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody, or antibodies to tumor necrosis factor family including OX40) or tumor vaccine for systemic disease but are now off therapy with documented stable systemic disease within 30 days of signing consent may be enrolled after discussion with the Merck & Co clinical team
Prior therapy with an anti-PD-1, anti PD-L1, anti-PD-L2, anti-CD137 antibody, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) agents
Prior or concurrent immunotherapy, including treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA-4 antibody; tumor vaccines; interferon, or interleukins.
Patients must not have received prior pembrolizumab or other anti-PD1/PDL1 therapies for their metastatic disease
No prior treatment with cancer immunotherapy including, but not limited to, other anti-CTLA-4, anti-PD-1, anti-PD-L1, and anti-programmed cell death ligand 2 anti- (PD-L2) antibodies, excluding therapeutic anticancer vaccines
Patients can be either naive for any previous systemic treatment or have had any number of prior systemic therapies. However, patients must not have received prior anticancer therapy with anti-PD1, anti-PD-L1, or anti-CTLA-4 immune checkpoint inhibitors.
Patients must not have received prior anticancer therapy with anti-PD1, anti-PD-L1, or anti- CTLA-4 immune checkpoint inhibitors.
Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137 or anti CTLA-4 antibody
Prior exposure to immune-mediated therapy, including but not limited to, other anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA 4), anti-PD1, anti –PD-L1, or anti-programmed death ligand 2 (PD-L2) antibodies, including therapeutic anticancer vaccines is NOT permitted
Has prior exposure to anti-PD1/PD-L1 or anti-CTLA4 therapy
Prior treatment with anti-PD-1/PD-L1, and anti-CTLA-4 is NOT allowed; prior intravesical Bacillus Calmette–Guérin (BCG) therapy is allowed
No prior exposure to immune-mediated therapy including, but not limited to, other anti CTLA-4, anti-PD-1, anti-PD-L1, and anti-programmed cell death ligand 2 (anti-PD-L2) antibodies, including therapeutic anticancer vaccines; the exception to this is those whose tumors are microsatellite instable-high (MSI-hi) and are refractory to anti-PD1 monotherapy
Prior checkpoint inhibitor therapy including anti-PD1, anti-PD-L1, anti-CTLA4, anti- CD137, or anti-PD-L2 therapy
Prior treatment with an anti-PD-1, anti-PD-L1 or anti-CTLA-4 antibody
Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti?CTLA-4, anti?PD-1, and anti?PD-L1 therapeutic antibodies\r\n* Prior cancer vaccines and cellular immunotherapy are permitted
Exclusion criteria related to study medication (any cancer immunotherapy including CD137 agonists, anti-PD-1, anti-PD-L1, or anti-CTLA4 or any MEK or ERK inhibitor)
Colorectal patients are excluded if they have had prior systemic treatment with an anti-CTLA4, anti-PD1 or PDL1 antibody; pancreatic patients are excluded if they have previously received anti-CTLA-4 therapy; prior PD-1 or PDL1 therapy will be permitted for pancreas patients
Patients may not have had prior therapy with a checkpoint inhibitor (e.g. anti-CTLA-4, anti-PD-1 or anti-PD-L1 therapy)
Prior therapy with atezolizumab or other immunotherapies including CD137 agonists, anti-programmed death (PD)-1, anti-cytotoxic T-lymphocyte associated protein 4 (CTLA-4), and anti-PD-L1 therapeutic antibodies
Prior history of receiving immune modulators including, but not limited to, anti-CTLA4, anti-PD1, anti-PD-L1
Tumor progression or recurrence during or after treatment with anti-PD1, anti-PDL1, anti-PDL2, anti-CTLA4, or other immune checkpoint inhibitor where the most recent dose was given within 3 months prior to study registration
Patients must not have received prior anticancer therapy with any immune checkpoint inhibitors such as anti-CLTA-4, anti-PD1, or anti-PD-L1
Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PDL-2 antibody
patients who have received all therapy known to confer clinical benefit (including anti-PD-1 or anti-PDL1 therapies, if relevant), or for whom no therapy of proven efficacy exists, or who are not amenable to standard therapies. Patients with anti- PD-1 or anti-PDL1 experience must have a minimum of 60 days between the last dose of the previous anti PD-1/PD-L1 and Cycle 1 Day 1 of BI 754091 treatment.
patients who are anti-PD-1 and anti-PDL-1naïve but have failed conventional treatment (excluding anti-PD-1 treatment), or for whom no therapy of proven efficacy exists, or who are not amenable to standard therapies.
No prior immune checkpoint inhibitors (e.g., anti-CTLA4, anti-PD-1 or anti-PDL1 are allowed
Patients with ongoing toxicities related to prior therapies targeting T cell coregulatory proteins (immune checkpoints) such as anti-PD-1, anti-PD-L1, or anti-CTLA-4 antibody are excluded
Patients must have no more than one prior systemic therapeutic regimen. This includes chemotherapy, biologic therapy, biochemotherapy, or investigational treatment. This does not include any therapies given in the adjuvant setting. No prior anti-CTLA4 therapy. Prior anti PD-1 or anti-PDL-1 antibody therapy is acceptable.
Prior exposure to any anti-PD-1 or anti-PD-L1 antibody, or any anti-cytotoxic T-lymphocyte-associated protein (CTLA) 4 antibodies
Patients who have received prior therapy with immune checkpoint inhibitors (e.g. anti-PD-1, anti-PD-L1, anti-LAG3, anti-CTLA-4) or immune costimulatory molecules (e.g. anti-CD137, anti-OX40, anti-GITR) directed agents
Prior therapy with anti-PD1, anti-PD-L1 or anti-cytotoxic T-lymphocyte protein (CTLA)-4 antibody
Subjects must have no prior exposure to immunotherapy, such as, but not limited to other anti-CTLA-4, anti-PD-1, or anti-PD-L1 antibodies excluding vaccines
Patients with a history of prior treatment with immunotherapy agents (including, but not limited to: interleukin [IL]-2, interferon, anti-PD-1, anti-PD-L1, anti-programmed cell death 1 ligand 2 [PD-L2], anti-cluster of differentiation [CD]137, anti-tumor necrosis factor receptor superfamily member 4 [OX-40], anti-CD40, or anti-cytotoxic t-lymphocyte-associated protein 4 [CTLA-4] antibodies)
Prior exposure to immune-mediated therapy, including but not limited to, other anti cytotoxic T-lymphocyte-associated protein 4 (CTLA 4), anti-PD-1, anti-PD-L1, or anti-PD-L2 antibodies, including therapeutic anticancer vaccines. Prior local intervesical chemotherapy or immunotherapy is allowed if completed at least 28 days prior to the initiation of study treatment.
For Dose escalation: subjects with cervical, ovarian, bladder and colorectal cancer (CRC), head and neck, gastric and hepatocellular cancer naive to immuno-oncology agents; 1st line melanoma and 1st line/2nd line NSCLC; Renal Cell Carcinoma naive to IO; NSCLC progressing while on or after therapy with anti-PD1/anti-PDL-1 and melanoma subjects progressed while-on or after treatment with anti-PD1 or anti-PDL1 with or without anti-CTLA-4.
Prior immunotherapy is allowed (previous immune checkpoint inhibitors; anti-CTLA-4, anti-PD-1, anti-PD-L1 and/or combinations), except for the patients enrolled to the immunotherapy naïve group of the phase IB dose expansion.
Patients with a history of prior treatment with anti-CTLA-4, anti-PD 1 antibody, or anti-PDL1 antibody
Prior exposure to immune-mediated therapy, including anti-PD-1, anti-PD-L1 (including durvalumab) or anti-CTLA-4 directed therapy (including tremelimumab); therapeutic anticancer vaccines are not included in this category; exposure to other investigational agents may be permitted after discussion with the study principal investigator (PI)
Prior exposure to immunotherapy including, but not limited to, anti-PD1 or anti-PDL1 antibodies is allowed but not required.
Prior treatment with cluster of differentiation (CD) 137 agonists or immune checkpoint blockade therapies, or anti-programmed cell death-1 (PD-1) or anti-PD-L1 therapeutic antibodies
Prior treatment with CD137 agonists or immune checkpoint-blockade therapies, including anti-CD40, anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies
Prior exposure to anti-PD-1, anti-PD-L1, CCR2/5, or anti-CTLA4 antibodies
Patients who have had prior exposure to immune-mediated therapy defined as prior exposure to T-cell and natural killer cell directed therapy (e.g. anti-PD-1, anti-PD-L1, anti-CD137, and anti-CTLA4, etc).
Prior treatment with cluster of differentiation (CD)137 agonists or immune checkpoint blockade therapies, including anti Cytotoxic T Lymphocyte-Associated 4 (CTLA4), anti-programmed death 1 (PD-1), and anti-PD-L1 therapeutic antibodies
Prior treatment with immune checkpoint blockade therapies (anti-cytotoxic T-lymphocyte-associated protein 4 [anti-CTLA-4], anti-programmed death-1 [anti-PD-1] or anti-PD-L1) or immune agonists (anti-cluster of differentiation [CD]137, anti-CD40, anti-OX40)
Patients who have had prior treatment with anti-PD1 or anti-CTLA4 therapy
Prior treatment with immune checkpoint blockade therapies (anti-cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], anti-programmed death-1 [PD-1] or anti-PD-L1) or immune agonists (anti-cluster of differentiation [CD] 137, anti-CD40, anti-OX40)
Patients who have had a grade one or grade two gastrointestinal adverse event during or after receiving anti-CTLA-4, anti-PD1 or anti-PD, without a colonoscopy verifying complete resolution of the adverse event
Immune-checkpoint inhibitors (i.e., anti-PD-1, anti-PD-L1, or anti-CTLA-4): 4 weeks
Melanoma immune checkpoint-naïve: Subjects must not have received immunotherapy with anti-PD-1, anti-PD-L1, or anti-CTLA-4 therapy. Exception: Prior anti?CTLA-4 in the adjuvant setting would be permitted.
Subjects must not have received prior immunotherapy with anti-PD-1, anti-PD-L1, or anti-CTLA-4 therapy.
Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-CTLA-4, anti PD-1, and anti PD-L1 therapeutic antibodies, or any other antibody or drug targeting T-cell costimulation.
PRIOR/CONCURRENT THERAPY CRITERIA: Prior treatment with an anti-PD-1 or anti-PDL1 is not required
Subject has had prior therapy with T-cell immune modulating antibodies, including anti-CTLA-4, anti-PD-1 or anti-PD-L1.
Patients must not have any prior exposure to immunotherapy such as, but not limited to anti-programmed death 1 (PD-1) or anti-PD-L1 antibodies; prior exposure to the following is allowed: anti-cytotoxic T lymphocyte antigen 4 (CTLA-4) antibodies, live attenuated vaccines, anti-EGFR agents and sargramostim (GM-GSF)
Subject had prior exposure to immunotherapy, including, but not limited to, other anti- CTLA-4,anti-PD-1, anti-PD-L1 monoclonal antibody or inhibitor, cell-based therapies, or cancer vaccines
Prior treatment with cluster of differentiation 137 (CD137) agonists or immune checkpoint blockade therapies, including anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA4), anti-programmed death-1 (PD-1), or anti-PD-L1 therapeutic antibodies
Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-CTLA4, anti-PD-1, and anti-PD-L1 therapeutic antibodies
Prior treatment with cluster of differentiation (CD) 137 agonists or immune checkpoint blockade therapies, anti-programmed death-1 (PD-1), and anti-PD-L1 therapeutic antibody
Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies
Prior exposure to tremelimumab or durvalumab or other anti-CTLA-4, anti-PD-1, anti-PD-L1 antibodies
No prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody.
Prior treatment with cluster of differentiation 137 (CD137) agonists or immune checkpoint blockade therapies, anti-programmed death-1 (anti-PD-1), and anti-PD-L1 therapeutic antibody
Received therapy with any immunotherapeutic agents including, but not limited to, any anti-PD1 or anti-PDL1 antibody therapy, with these exceptions: Melanoma patients having received and progressed on anti-CTLA4 (cyctotoxic T lymphocyte-associated antigen 4) may participate in the trial; Bladder cancer patients having received intra-vesical BCG may participate in the trial.
Prior treatment with an anti PD-1, anti PD-L1, or anti CTLA-4 agent; participants who entered clinical remission with one of those agents and proceeded to ASCT without intervening relapse may be eligible after discussion with the study chair; note that for patients who enter remission with checkpoint blockade therapy, this will not count towards the 3 lines of prior therapy
Prior immunotherapies including but not limited to CD137, anti-PD-1, anti-PD-L1, and CTLA4.
CD137 agonists, immune checkpoint inhibitors including but not limited to CTLA-4, anti-PD-1, and anti-PD-L1 therapies
Patients who have had prior exposure to checkpoint blockade therapy, such as anti-PD-1/PD-L1, anti-cytotoxic T-lymphocyte associated protein 4 (CTLA4), anti-CD137, and anti-OX40 antibody therapy, are not eligible
Prior anti-cancer therapy including: Fludarabine or alemtuzumab within 12 months prior to D1C1; radioimmunoconjugate within 12 weeks prior to D1C1; monoclonal antibody or antibody drug conjugate (ADC) within 5 half-lives or 4 weeks prior to D1C1 ; radiotherapy, chemotherapy, hormonal therapy, or targeted small-molecule therapy within 2 weeks prior to D1C1; anti-programmed death-1 (anti-PD-1), anti-programmed death-ligand 1 (anti-PD-L1), anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4), anti-CD137/41-BB agonist, or anti-CD40 agonist antibodies
Prohibited prior treatments and/or therapies: a) prior therapy with an anti-killer cell immunoglobulin-like receptors (KIR), anti-programmed cell death 1 (PD-1), or anti-programmed cell death ligand 1 (PD-L1), antibody ; b) prior treatment regimens with any immune cell modulating antibody such as anti-cluster of differentiation (CD)137 and anti-OX40; however, prior anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4) therapy is allowed if the last dose is 101 days or more from the first dose of study drug; c) exposure to any other investigational drug within 2 weeks prior to the first dose of study drug (within 101 days for anti-CTLA4 therapy); d) any anti-cancer therapy (e.g., chemotherapy, biologics, vaccines, radiotherapy with curative intent, or hormonal treatment) within 2 weeks prior to the first dose of study drug administration (within 101 days for anti-CTLA4 therapy administration); e) use of non-oncology vaccines containing live virus for prevention of infectious diseases within 4 weeks prior to study drug; the use of the inactivated seasonal influenza vaccine (Fluzone) is allowed; f) systemic corticosteroid at immunosuppressive doses (> 10 mg/day of prednisone or equivalent), must be discontinued at least 2 weeks prior to enrollment
Prior therapy with anti-PD-1, anti-PDL1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody
Prior exposure to doxorubicin, PLD or any other anthracycline, motolimod and other TLR agonists, MEDI4736 or checkpoint inhibitors, such as anti-CTLA4 and anti-PD1/anti-PD-L1 antibodies.
Received prior therapies: ibrutinib, or other BTK inhibitor and/or anti-PD1, anti-PD-L1, anti-PD-L2, anti-CD137, or CTLA-4 antibody
Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-cluster of differentiation (CD)137; patients who received anti-cytotoxic T-lymphocyte antigen 4 (CTLA4) (ipilimumab, tremelimumab) will NOT be excluded and are eligible for inclusion
Prior exposure to any anti-PD-1 or anti-PD-L1 antibody or anti CTLA4
Prior BTK inhibitor or anti PD1, anti PDL1, anti PD-L2 and anti-CD137, anti-cytotoxic T-lymphocyte associated antigen (CTLA-4) antibody
Patients with a history of prior treatment with anti-PD-1, anti-PD-ligand (L)1, anti-PD-L2, anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4) antibodies, or who have received both GVAX or CRS-207 will be excluded
Prior exposure to tremelimumab or MEDI4736 or other anti-CTLA-4, anti-PD-1, anti-PDL1 antibodies
Ocular melanoma; and have received no more than one line of systemic therapy for metastatic disease. Patients must not have received immune modifying agents (eg. anti PD-L1, anti PD-1, anti CTLA4, TNF agonist, etc.) for metastatic disease, or
Cutaneous/acral melanoma; and have 1) only previously received systemic therapy for advanced/metastatic disease with the following therapies: BRAF and MEK inhibitors, anti PD-L1, anti PD-1, or anti-CTLA4 and 2) have received checkpoint inhibitor (anti PD-L1, anti PD-1, or anti-CTLA4) based treatment as most recent line of therapy on which disease progressed, as long as progression did not occur in the first 3 months of receiving checkpoint inhibitor treatment. Arm 2 only:
Prior histone deacetylase (HDAC) inhibitor and/or anti-PD1, anti-PDL1, anti-PD-L2, anti-CD137 or anti-cytotoxic T- lymphocyte associated antigen 4 (CTLA-4) antibody allowed as long patient received clinical benefit from it, best response was not progressive disease and it was not the most recent treatment
Prior therapy with any antibody/drug targeting T-cell co-regulatory proteins (immune checkpoints) such as anti-PD-1, anti-PD-L1, or anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) antibodies. For subjects with metastatic melanoma, prior treatment with CTLA-4-blocking antibody is permissible.
Participants in the Monotherapy Expansion Cohort must have one of the following advanced or recurrent malignancies: cutaneous melanoma showing primary progression following treatment with an anti-programmed cell death (PD) or anti-PDL1 regimen; or anti-PD1 or anti-PD-L1 treatment-naïve colorectal or gastric cancer, including gastroesophageal junction cancer of Siewert Type II and Type III.
Participants in the Combination Expansion Cohorts must have one of the following advanced or recurrent malignancies: non-small cell lung adenocarcinoma or cutaneous melanoma showing primary progression following treatment with an anti-PD1 or anti-PD-L1 regimen; or anti-PD1 or anti-PD-L1 treatment-naïve colorectal or gastric cancer, including gastroesophageal junction cancer of Siewert Type II and Type III.
Previous treatment with anti-CD27 antibody, ipilimumab or other anti-CTLA-4 targeted therapies. Previous therapy with other checkpoint blockers such as anti-PD-1 or anti-PD-L1 is acceptable, unless treatment was discontinued for intolerance.
Prior treatment with an anti-PD-1, anti-PD-L1, or anti-PD-L2 antibody; neuroblastoma (NB)-patients who have received prior anti-cytotoxic T-lymphocyte antigen (CTLA)-4 antibody therapy are eligible assuming such therapy was discontinued within 28 days of enrollment
Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or CTLA-4 antibody.
Prior treatment with cluster of differentiation (CD) 137 agonists or immune checkpoint blockade therapies, anti-programmed death-1 (anti-PD-1), and anti-PD-L1 therapeutic antibodies
Recipient of any blood product and immunotherapy (such as anti-PD1, anti-PDL-1 and anti-CTLA4) within 3 months of enrollment;
Prior treatment with ibrutinib or other BTK inhibitor anti-CD137 or CTLA-4 antibody. The following are exceptions to this criterion: Subjects previously treated with an anti-PD1, anti-PD-L1, or anti-PD-L2 antibody.
Prior exposure to immunotherapy, such as, but not limited to, other anti-CTLA-4, anti-PD-1, or anti-PD-L1 antibodies, excluding therapeutic cancer vaccines
Patients who have received prior anti-CTLA4 or anti-PD1 therapy less than 8 weeks prior to enrollment
NSCLC Cohort (CIT-Treated): Participants with histologically confirmed incurable, advanced NSCLC previously treated with anti-PD-L1/PD-1 with or without anti-CTLA-4 (investigational or approved)
Colorectal cancer (CRC) Cohort: Participants with histologically confirmed incurable, advanced adenocarcinoma of the colon or rectum not previously treated with anti-PD-L1/PD-1 and/or anti-CTLA-4 (investigational or approved)
In the NSCLC CIT-Treated exploration cohort in Phase 1b, the most recent systemic treatment should have been anti-PD?L1/PD-1 and/or anti-CTLA-4 as monotherapy or in combination
In the NSCLC CIT-Naïve expansion cohort in Phase 1b, prior treatment with anti-PD?L1/PD-1 and/or anti-CTLA-4 (investigational or approved) is not allowed
No prior exposure to immune-mediated therapy defined as prior exposure to T-cell and natural killer cell directed therapy (e.g., anti-PD-1, anti-PD-L1, anti-CD137, and anti-CTLA4, etc).
Participants with a history of treatment with an anti-PD-1, anti-PD-L1, anti-CTLA-4 or other investigational agents that target immune checkpoint inhibitors
Prior treatment with cluster of differentiation (CD) 137 agonists or immune checkpoint blockade therapies, anti PD1, and anti-PD-L1 therapeutic antibody
Prior treatment with checkpoint inhibitors and other immunotherapy treatments, including anti-LAG-3, anti-PD-1, anti-PD-L1 or anti-CTLA-4 antibodies, if less than 5 half lives before study drug administration
Prior therapy with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti CTLA 4, or anti-CD38 antibody, or allogeneic stem cell transplantation
Histologically or cytologically documented cancer to which anti-PD1 or anti-PDL1 are approved therapies
History of prior treatment with immune checkpoint antibodies (e.g. anti-PD1, anti-PDL1, anti-CTLA4 antibody) or co-stimulatory agonist antibodies (e.g. anti-41BB, anti-OX40)\r\n* Prior intravesical treatment with Bacillus Calmette-Guerin (BCG) is allowed; however, the last dose must be at least 6 weeks from time of enrollment and patients must have documented progressive disease at least 6 weeks from completion of last BCG
Patients that plan to receive off-label use of anti-PD1 or anti-PDL1
Patients must not have had prior exposure to any immune checkpoint inhibitors including anti-PD-1, anti-PD-L1 gents, anti-PD-L2 agents, or anti-CTLA-4 monoclonal antibodies
Patients who have previously received anti-PD1 or anti-PD-L1 therapy; patients who have previously received anti-CTLA-4 therapy (e.g. ipilimumab) are eligible for study
Prior therapy with any antibody/drug that targets the T cell coregulatory proteins, including but not limited to, anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti-OX-40,and anti-CD40 antibodies. However, half the patients must have progressed on anti Cytotoxic T lymphocyte-associated antigen 4 (anti-CTLA4) monoclonal antibody therapy