Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as PD-1 inhibitor, PD1, Retifanlimab, Epacadostat, INCB024360, MGA012, INCMGA 0012, Retifanlimab-dlwr
INCMGA00012 · 34 trials · 64 indications
PFS was defined as the time from the date of randomization to the date of the first documented disease progression (PD), according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) by blinded independent central review committee (BICR), or death due to any cause, whichever occurred first. PD: progression of a target or non-target lesion or presence of a new lesion.
Overall survival was defined as the time between the date of randomization and the date of death due to any cause.
ORR was defined as the percentage of participants who had a complete response (CR), disappearance of all target lesions or partial response (PR), \>=30% decrease in the sum of the longest diameter of target lesions per RECIST v1.1 by investigator determination.
ORR was defined as the percentage of participants who had complete response (CR) or partial response (PR) per RECIST v1.1 by investigator determination.
ORR was defined as the percentage of participants who had a complete response (CR), disappearance of all target lesions or partial response (PR), \>=30% decrease in the sum of the longest diameter of target lesions per RECIST v1.1 by investigator determination. Responses are based on investigator assessments per RECIST 1.1 without confirmation using all available scans.
The primary efficacy endpoint for the study is the ORR. The ORR is defined as the number of patients with CR and PR divided by the number of patients in the analysis set. Tumor response will be defined as best response based on local investigator's assessment according to RECIST criteria v.1.1.
Overall survival is defined as the time interval from date of treatment start to date of a documented death event (death due to any cause) or date of censoring. If a patient has not had an event, OS will be censored at the date of last follow up.
Overall survival is defined as the time interval from date of treatment start to date of a documented death event (death due to any cause) or date of censoring. If a patient has not had an event, OS will be censored at the date of last follow up.
Overall survival is defined as the time interval from date of treatment start to date of a documented death event (death due to any cause) or date of censoring. If a patient has not had an event, OS will be censored at the date of last follow up.
DFS is defined the occurrence of progression of local disease, distant metastases, second primary or death. 1-year DFS, will be analyzed using the Kaplan-Meier method and be compared using a 0.05-level one-sided two-proportion test. DFS will be compared among the three subgroups: favorable response subgroup, intermediate response subgroup, unfavorable response subgroup.
Defined as the proportion of participants having a best objective response of complete response (CR) or partial response (PR), as determined by investigator assessment per Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1.
Objective radiographic response (ORR), as measured by modified Response Assessment in Neuro-Oncology (RANO) criteria. ). The response is classified as Complete Response (CR), Partial Response (PR), Stable Disease (SD), and Progressive Disease (PD).
PFS was defined as the time from the date of randomization to the date of the first documented progression, as determined by investigator assessment per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1), or death due to any cause, whichever occurred first.
RNA expression analysis (Nanostring) to determine changes in Interferon gamma expression signature before and during treatment
Flow cytometry to determine changes in immune infiltrate in the tumor before and during treatment
Multicolor immunohistochemstry to determine changes in immune infiltrate in the tumor before and during treatment
Defined as the proportion of participants having a CR or PR according to RECIST v1.1, as assessed by Independent Central Review committee
Will be determined by the number, frequency, duration, and severity of adverse events (AEs) using Common Terminology Criteria for Adverse Events (CTCAE) v 5.0; laboratory tests and vital signs.
Radiographic response rates in target tumors according to tumor-associated criteria: * VS, non-VS, and meningiomas: Dombi criteria (2013) * Ependymomas: RECIST 1.12
ORR was defined as the percentage of participants with a best overall response of complete response (CR) or partial response (PR), per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (v1.1), as determined by the investigator, at any post-Baseline visit until new anti-cancer therapy or first Progressive Disease. CR: disappearance of all target and non-target lesions and no appearance of any new lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to \<10 millimeters (mm). PR: complete disappearance or at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum diameters, no new lesions, and no progression of non-target lesions.
ORR is defined as the percentage of participants who have a confirmed complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) based on blinded independent central review (BICR).
ORR is defined as the proportion of participants who have a confirmed complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 based on blinded independent central review (BICR).
To determine the safety of fixed doses of DEC205mAb-NY-ESO-1 fusion protein with adjuvant poly-ICLC given as a vaccine in combination with INCB024360 300mg, number of Participants with Dose Limiting Toxicities is reported
Percentage of Participants with Progression Free Survival Using irRC Criteria for Phase II Patients are reported. irRC criteria disease progression is defined as at least 25% increase in tumor burden compared with nadir (at any single time point) in two consecutive observations at least 4 weeks apart.
All patients enrolled in this study will be eligible for the analysis of toxicity. The toxicity rate will be estimated using a one-sided, 95%, exact binomial confidence interval (Clopper-Pearson).
Dose Limiting Toxicities DLTs Adverse Events The National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 Treatment related Dose Limiting Toxicities (DLTs) will be monitored through the first 2 cycles of the study therapy (28 days). Follow up safety assessments will continue beyond the first 28 days and throughout the treatment on the trial to monitor for late onset treatment related adverse effects or toxicities
* Safety will be defined as a \< 33% treatment-related DLT rate related to vaccination alone or in combination with retifanlimab, by the end of the DLT observation period for a given cohort. * A DLT will be defined as any grade 3 toxicity or greater according to CTCAE v5 considered at least possibly related to study treatment (exceptions are listed in the protocol). * The DLT observation period begins with date of first vaccine administration and continues for 30 days from administration of first dose of retifanlimab. For patients in Cohort A, this is Day 87 (first dose of retifanlimab is given with vaccine Dose 3 on Day 57), and for patients in Cohort B, this is Day 30 (first dose of retifanlimab is given with vaccine Dose 1 on Day 1).
The recommended phase 2 dose (RP2D) is defined as the dose level immediately below the maximally administered dose at which 0 or 1 of a cohort of 3 to 6 patients experienced a dose-limiting toxicity (DLT) during first 2 cycles.
Neoadjuvant Rectal Score (NAR Score) is calculated by following formula: NAR = (\[5pN \- 3(cT - pT) + 12\]2)/9.61 (with higher scores representing poorer prognosis), where cT=clinical tumor stage, pT=pathologic tumor stage, and pN=pathologic nodal stage.
Defined as any adverse event either reported for the first time or worsening of a pre-existing event after first dose of study drug.
Defined as any adverse event either reported for the first time or worsening of a pre-existing event after first dose of study drug.
Defined as any adverse event either reported for the first time or worsening of a pre-existing event after first dose of study drug.
Defined as any adverse event either reported for the first time or worsening of a pre-existing event after first dose of study drug.
A TEAE is any AE either reported for the first time or worsening of a pre-existing event after first dose of epacadostat, pembrolizumab, or chemotherapy. Serious adverse event is defined as an event that meets 1 of the following criteria: is fatal or life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability, incapacity, or a substantial disruption of a person's ability to conduct normal life functions, constitutes a congenital anomaly or birth defect,is a medically important event that may jeopardize the participant or may require medical or surgical intervention to prevent 1 of the outcomes listed above.
A DLT was defined as the occurrence of any of the protocol-specified toxicities occurring up to and including Day 28 for the cohorts where mFOLFOX6 and nab-paclitaxel/gemcitabine are administered and Day 21 for all other chemotherapy regimens in Phase 1, except those with a clear alternative explanation (eg, disease progression) or transient (≤ 72 hours) abnormal laboratory values without associated clinically significant signs or symptoms based on investigator determination.
ORR was defined as the percentage of participants having a complete response (CR) or partial response (PR) as determined by investigator assessment of radiographic disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
Safety is based on evaluation of adverse events (AEs) and serious adverse events (SAEs) from the time of study drug administration through the End of Study visit.
Maximum Tolerated Dose of INCMGA00012
Adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug/treatment
ORR was defined as the percentage of participants having a complete response (CR) or partial response (PR) as determined by investigator assessment of radiographic disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
A DLT was defined as occurrence of any treatment-emergent adverse event (TEAE) in Phase 1 Parts 1 and 2. DLT included all TEAE of specified grades such as 1) Hematologic toxicities - any Grade 4 thrombocytopenia or neutropenia, anemia, febrile neutropenia, ≥ Grade 3 hemolysis, thrombocytopenia and 2) Nonhematologic toxicities - Grade 4 AE, nausea, vomiting, or diarrhea, electrolyte abnormality, ≥ Grade 3 aspartate aminotransferase (AST), alanine aminotransferase (ALT), or total bilirubin elevation, Grade 2 AST/ALT with symptomatic liver inflammation, AST or ALT \> 3 × upper limit of normal (ULN) and concurrent total bilirubin \> 2 × ULN without initial findings of cholestasis, and any other ≥ Grade 3 toxicity. A TEAE is any AE either reported for the first time or worsening of a pre-existing event after first dose of study drug and up to 100 days after last dose of study drug.
A DLT was defined as occurrence of any treatment-emergent adverse event (TEAE) in Phase 1 Parts 1 and 2. DLT included all TEAE of specified grades such as 1) Hematologic toxicities - any Grade 4 thrombocytopenia or neutropenia, anemia, febrile neutropenia, ≥ Grade 3 hemolysis, thrombocytopenia and 2) Nonhematologic toxicities - Grade 4 AE, nausea, vomiting, or diarrhea, electrolyte abnormality, ≥ Grade 3 aspartate aminotransferase (AST), alanine aminotransferase (ALT), or total bilirubin elevation, Grade 2 AST/ALT with symptomatic liver inflammation, AST or ALT \> 3 × upper limit of normal (ULN) and concurrent total bilirubin \> 2 × ULN without initial findings of cholestasis, and any other ≥ Grade 3 toxicity. A TEAE is any AE either reported for the first time or worsening of a pre-existing event after first dose of study drug and up to 100 days after last dose of study drug.
An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (e.g., a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A TEAE is any AE either reported for the first time or worsening of a pre-existing event after first dose of study drug and up to 100 days after last dose of study drug.
ORR was defined as the percentage of participants having a complete response (CR) or partial response (PR) as determined by investigator assessment of radiographic disease per RECIST v1.1. CR per RECIST v 1.1 was defined as disappearance of all target lesions. PR per RECIST v 1.1 was defined as At least a 30% decrease in the sum of diameters (SOD) of target lesions, taking as reference the Baseline sum diameters. Data is reported as per dose received by the participants with a particular cancer type. CR per Cheson criteria was defined as complete disappearance of all detectable clinical evidence of disease and disease-related symptoms. PR per Cheson criteria was defined as at least a 50% decrease in sum of the product of the diameters (SPD) of up to 6 of the largest dominant nodes or nodal masses.
PFS is defined as the time from randomization to the first documented progressive disease per RECIST v1.1 or death due to any cause, whichever occurs first.
OS rate is defined as the proportion of participants alive 9 months after the start of treatment.
An adverse event is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after a participant provides informed consent. A TEAE is any adverse event either reported for the first time or worsening of a pre-existing event after first dose of study drug. Serious adverse event (SAE) is defined as an event that meets 1 of the following criteria: is fatal or life threatening, results in persistent or significant disability or incapacity, constitutes a congenital anomaly or birth defect, is clinically meaningful (i.e. defined as an event that jeopardizes the participant or requires potential medical or surgical intervention to prevent 1 of the outcomes listed above) or requires inpatient hospitalization or prolongation of existing hospitalization.
ORR was percentage of participants with best overall response \[complete response (CR) or partial response (PR)\], per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
| Arm | Type | Description |
|---|---|---|
| Group A : carboplatin+paclitaxel+placebo | PLACEBO_COMPARATOR | Participants will receive carboplatin on Day 1,paclitaxel on Day1,8, 15, and placebo on Day 1 of each 28 day cycle |
| Group B : carboplatin+paclitaxel+retifanlimab | EXPERIMENTAL | Participants will receive carboplatin on Day 1,paclitaxel on Day1,8, 15, and retifanlimab on Day 1 of each 28 day cycle |
| INCMGA00012 + chemotherapy (nonsquamous NSCLC) | EXPERIMENTAL | INCMGA00012 with pemetrexed + cisplatin OR carboplatin followed by INCMGA00012 plus pemetrexed until progression. |
| Placebo + chemotherapy (nonsquamous NSCLC) | ACTIVE_COMPARATOR | Placebo with pemetrexed + cisplatin OR carboplatin followed by placebo plus pemetrexed until progression. Participants assigned to placebo + chemotherapy will have the option of receiving open-label monotherapy INCMGA00012 in a crossover period after documentation of progressive disease. |
| INCMGA00012 + chemotherapy (squamous NSCLC) | EXPERIMENTAL | INCMGA00012 with carboplatin + paclitaxel OR nab-paclitaxel followed by INCMGA00012 until progression. |
| Placebo + chemotherapy (squamous NSCLC) | ACTIVE_COMPARATOR | Placebo with carboplatin + paclitaxel OR nab-paclitaxel followed by placebo until progression. Participants assigned to placebo + chemotherapy will have the option of receiving open-label monotherapy INCMGA00012 in a crossover period after documentation of progressive disease. |
| Pembrolizumab 200 mg + Epacadostat 100 mg BID | EXPERIMENTAL | Pembrolizumab + epacadostat |
| Pembrolizumab 200 mg + placebo BID | ACTIVE_COMPARATOR | Pembrolizumab + placebo |
| Pembrolizumab + Epacadostat | EXPERIMENTAL | - |
| SoC (Sunitinib or Pazopanib) | ACTIVE_COMPARATOR | Standard of care (SoC) (sunitinib or pazopanib monotherapy). |
| Pembrolizumab | EXPERIMENTAL | - |
| EXTREME | ACTIVE_COMPARATOR | EXTREME regimen includes cetuximab + cisplatin or carboplatin + 5-fluorouracil. |
| Interventional arm | EXPERIMENTAL | Patients will receive INCMGA00012 500 mg by intravenous infusion on Day1 of each cycle. |
| Regimen A: Retifanlimab+RT+bevacizumab | EXPERIMENTAL | * Retifanlimab will be given intravenously over the course of 30 to 60 minutes at a dose of 500 mg on Day 1 of each 28-day cycle. * Bevacizumab will be given intravenously at a dose of 10 mg/kg on Days 1 and 15 of each 28-day cycle. * Ten fractions of radiation therapy will be given at a dose of 3.5 Gy per fraction * Retifanlimab and bevacizumab will be started approximately two weeks before the first day of radiation therapy * Treatment may continue for up to two years. |
| Regimen B: Retifanlimab+RT+bevacizumab+epacadostat | EXPERIMENTAL | * Retifanlimab will be given intravenously over the course of 30 to 60 minutes at a dose of 500 mg on Day 1 of each 28-day cycle. * Bevacizumab will be given intravenously at a dose of 10 mg/kg on Days 1 and 15 of each 28-day cycle. * Ten fractions of radiation therapy will be given at a dose of 3.5 Gy per fraction * Retifanlimab and bevacizumab will be started approximately two weeks before the first day of radiation therapy * Epacadostat will be administered orally at 400 mg BID. * Treatment may continue for up to two years. |
| Chemoradiation based on HPV ctDNA response | EXPERIMENTAL | All participants will receive CRT for one cycle (4 weeks), while undergoing HPV ctDNA testing. Investigators will then modify the treatment plan based on HPV ctDNA response: * Favorable response: Dose reduction (total of 28 fractions of CRT) * Intermediate response: Standard dose (total of 30 fractions of CRT) * Unfavorable response: Dose-intensification (total of 34 fractions of CRT) and Retifanlimab to follow CRT |
| Treatment (retifanlimab, tuparstobart, and verzistobart) | EXPERIMENTAL | INDUCTION PHASE: Patients receive retifanlimab IV over 30 minutes every 4 weeks and tuparstobart and verzistobart IV over 30 minutes every 2 weeks. Treatment continues for up to day 169 in the absence of disease progression or unacceptable toxicity. Patients undergo computed tomography CT/MRI during screening and on study and blood sample collection on study and may undergo during screening. Patients may also undergo a tumor biopsy during screening and on study. MAINTENANCE PHASE: Patients receive retifanlimab, tuparstobart and verzistobart IV over 30 minutes every 6 weeks. Treatment continues for up to day 715 in the absence of disease progression or unacceptable toxicity. Patients undergo CT/MRI on study and blood sample collection on study and may undergo during follow-up. Patients may also undergo tumor biopsy on study and during follow-up. |
| Arm A (failed prior TMZ + one other alkylating chemotherapy) | EXPERIMENTAL | Subjects in Arm A are alkylator-refractory and at high risk for progression of disease, have failed temozolmide and another alkylating agent. Subjects in Arm A will receive 28-day cycles of treatment, with ATRA 45mg/m2/day given orally in two equally divided doses on days 1 through 14 and retifanlimab 500mg IV on day 1. |
| Arm B (failed only one prior alkylating chemotherapy) | EXPERIMENTAL | Subject in Arm B are patients who have failed only one prior alkylating chemotherapy regimen and have gone at least 12 months since the last treatment. Subjects in Arm B will receive 28-day cycles of treatment, with ATRA 45mg/m2/day given orally in two equally divided doses on days 1 through 14 and retifanlimab 500mg IV on day 1. |
| Arm C (surgical arm, ATRA alone pre-operatively) | EXPERIMENTAL | Subject in Arm C will receive ATRA 45mg/m2/day orally in two equally divided doses for 14 days pre-surgery, then undergo surgery. Following surgery all patients will receive 28-day cycles of treatment, with ATRA 45mg/m2/day given orally in two equally divided doses on days 1-14 and retifanlimab 500mg IV on day 1. |
| Arm D (surgical arm, ATRA + retifanlimab pre-operatively) | EXPERIMENTAL | Subject in Arm D will receive the combination of ATRA 45mg/m2/day orally in two equally divided doses for 14 days pre-surgery plus a 500mg IV dose of retifanlimab 14 days prior to the date of surgery. Following surgery all patients will receive 28-day cycles of treatment, with ATRA 45mg/m2/day given orally in two equally divided doses on days 1-14 and retifanlimab 500mg IV on day 1. |
| Treatment Group 1: Retifanlimab Monotherapy | EXPERIMENTAL | Retifanlimab will be administered intravenously every 4 weeks. Placebos for INCAGN02385 and INCAGN02390 will be administered intravenously every 2 weeks. |
| Treatment Group 2: Retifanlimab + INCAGN02385 | EXPERIMENTAL | Retifanlimab will be administered intravenously every 4 weeks. INCAGN02385 and Placebo for INCAGN02390 will be administered intravenously every 2 weeks. |
| Treatment Group 3: Retifanlimab + INCAGN02385 + INCAGN02390 | EXPERIMENTAL | Retifanlimab plus INCAGN02385 and INCAGN02390 will be administered intravenously. Retifanlimab will be administered intravenously every 4 weeks. INCAGN02385 and INCAGN02390 will be administered every 2 weeks. |
| Capecitabine, oxaliplatin and retifanlimab | EXPERIMENTAL | IV and PO Capecitabine 1000 mg/m2, oxaliplatin 130 mg/m2, every three weeks (up to 2 cycles) IV retifanlimab 500mg, every four weeks |
| Group A - retifanlimab | EXPERIMENTAL | Select participants naïve to checkpoint inhibitors will be administered retifanlimab intravenously |
| Group B - retifanlimab | EXPERIMENTAL | Select participants naïve to checkpoint inhibitors will be administered retifanlimab intravenously |
| Group C - retifanlimab + epacadostat | EXPERIMENTAL | Select participants who are allowed on prior checkpoint inhibitors will be administered retifanlimab intravenously in combination with oral epacadostat (IDO1 inhibitor) |
| Group D - retifanlimab + pemigatinib | EXPERIMENTAL | Select participants who are allowed on prior checkpoint inhibitors will be administered retifanlimab intravenously in combination with oral pemigatininb (FGFR 1,2,3 inhibitor) |
| Group E - retifanlimab + epacadostat | EXPERIMENTAL | Select participants naïve to checkpoint inhibitors will be administered retifanlimab intravenously in combination with oral epacadostat |
| Group F - retifanlimab + INCAGN02385 and INCAGN02390 | EXPERIMENTAL | Select participants who are allowed on prior checkpoint inhibitors will be administered retifanlimab in combination with INCAGN02385 and INCAGN02390 intravenously |
| Treatment (pelareorep, retifanlimab) | EXPERIMENTAL | Patients receive pelareorep IV over 60 minutes on days 1, 2, 15, and 16. Patients also receive INCMGA00012 IV over 60 minutes on day 3. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
| Cohort A | EXPERIMENTAL | Subjects in this arm (N=16) receive a single priming dose of both INCMGA00012 (500mg) and INCAGN01876 (300mg) prior to stereotactic radiosurgery (SRS), then undergo SRS (8 Gy x 3 fractions). Following SRS, INCMGA00012 (500mg IV every 4 weeks) and INCAGN01876 (300mg IV every 2 weeks) are resumed and continued until disease progression, unacceptable toxicity, or for 2 years, whichever occurs first. |
| Cohort B sub-arm #1 | EXPERIMENTAL | Subjects in this arm (N=8) receive neoadjuvant immunotherapy INCMGA00012 (500mg) + INCAGN01876 (300mg) + SRS. Subjects then undergo surgery. Postoperatively, the immunotherapy combination of INCMGA00012 (500 mg IV every 4 weeks) and INCAGN01876 (300mg IV every 2 weeks) is resumed and continued until disease progression, unacceptable toxicity, or for 2 years, whichever occurs first. |
| Cohort B sub-arm #2 | EXPERIMENTAL | Subjects in this arm (N=8) receive neoadjuvant immunotherapy INCMGA00012 + INCAGN01876 (without SRS). Subjects then undergo surgery. Postoperatively, the immunotherapy combination of INCMGA00012 (IV every 4 weeks) and INCAGN01876 (IV every 2 weeks) is resumed and continued until disease progression, unacceptable toxicity, or for 2 years, whichever occurs first. |
| Sub-study A (brigatinib) - CLOSED TO ENROLLMENT | EXPERIMENTAL | Subjects treated in this arm will receive brigatinib 90 mg by mouth daily for 7 days and then increased to 180 mg by mouth daily if the drug is tolerated. |
| Sub-study B (neratinib) | EXPERIMENTAL | The first three participants treated in this arm will receive neratinib 200 mg mg by mouth daily. If these participants tolerate the medication well, subsequent participants will receive neratinib 240 mg by mouth daily. |
| Experimental: sub-study C (retifanlimab plus bevacizumab) | EXPERIMENTAL | Subjects on this arm will receive retifanlimab by IV infusion at a dose of 375 mg every 3 weeks on a continuous schedule for 48 weeks. Subjects will also receive bevacizumab by IV infusion at a dose of 7.5 mg/kg every 3 weeks on an intermittent schedule. One cycle last 42 days and the study will last for 52 total weeks (48 treatment weeks and 4 follow-up weeks). |
| Retifanlimab: Chemotherapy: Naïve | EXPERIMENTAL | - |
| Retifanlimab: Chemotherapy: Refractory | EXPERIMENTAL | - |
| Melanoma: retifanlimab 500 mg | EXPERIMENTAL | Participants with melanoma received retifanlimab 500 milligrams (mg) every 4 weeks (Q4W), administered by intravenous (IV) infusion over 30 minutes on Day 1 of each 28-day cycle. |
| NSCLC: retifanlimab 500 mg | EXPERIMENTAL | Participants with non-small cell lung cancer (NSCLC) received retifanlimab 500 mg Q4W, administered by IV infusion over 30 minutes on Day 1 of each 28-day cycle. |
| UC: retifanlimab 500 mg | EXPERIMENTAL | Participants with urethelial carcinoma (UC) received retifanlimab 500 mg Q4W, administered by IV infusion over 30 minutes on Day 1 of each 28-day cycle. |
| RCC: retifanlimab 500 mg | EXPERIMENTAL | Participants with renal cell carcinoma (RCC) received retifanlimab 500 mg Q4W, administered by IV infusion over 30 minutes on Day 1 of each 28-day cycle. |
| Retifanlimab 500 mg | EXPERIMENTAL | Retifanlimab 500 milligrams (mg) intravenously every 4 weeks (Q4W). |
| Pembrolizumab + Chemotherapy + Epacadostat | EXPERIMENTAL | Participant received pembrolizumab 200 mg intravenous (IV) infusion, every 3 weeks (Q3W) on Day 1 of each 21 day cycle for up to 35 cycles + epacadostat 100 mg tablets, orally, twice daily (BID) in each 21 day cycle for up to 35 cycles + platinum-doublet chemotherapy (pemetrexed 500 mg/m\^2 IV infusion, Q3W + cisplatin 75 mg/m\^2 IV infusion, Q3W or carboplatin 5-6 mg/mL/min IV infusion Q3W for 4 cycles followed by pemetrexed maintenance; or paclitaxel 200 mg /m\^2 IV infusion, Q3W + carboplatin 5-6 mg/mL/min IV infusion Q3W for 4 cycles). |
| Pembrolizumab + Chemotherapy + Placebo | EXPERIMENTAL | Participant received pembrolizumab 200 mg IV infusion, Q3W on Day 1 of each 21 day cycle for up to 35 cycles + epacadostat matching placebo tablets, orally, BID in each 21 day cycle for up to 35 cycles + platinum-doublet chemotherapy (pemetrexed 500 mg/m\^2 IV infusion, Q3W + cisplatin 75 mg/m\^2 IV infusion, Q3W or carboplatin 5-6 mg/mL/min IV infusion Q3W for 4 cycles followed by pemetrexed maintenance; or paclitaxel 200 mg /m\^2 IV infusion, Q3W + carboplatin 5-6 mg/mL/min IV infusion Q3W for 4 cycles). |
| Pembrolizumab + Placebo | ACTIVE_COMPARATOR | Participants received pembrolizumab 200 mg by IV infusion, Q3W starting on Day 1 of each cycle for up to 35 administrations in combination with matching placebo orally, twice daily. Placebo administration was discontinued after the implementation of protocol amendment 05. |
| Arm I (CDX-1401, poly ICLC) | EXPERIMENTAL | Patients receive DEC-205/NY-ESO-1 fusion protein CDX-1401 and poly ICLC as in Phase I. |
| Arm II (CDX-1401, poly ICLC, IDO1 inhibitor INCB024360) | EXPERIMENTAL | Patients receive DEC-205/NY-ESO-1 fusion protein CDX-1401, poly ICLC, and IDO1 inhibitor INCB024360 as in Phase I. |
| Retifanlimab + 9-ING-41 + Chemotherapy | EXPERIMENTAL | 1. Chemotherapy: oxaliplatin 85 mg/m2 IV, leucovorin 400 mg/m2 IV, irinotecan 150 mg/m2 IV, and 5-FU continuous IV infusion 2400 mg/m2 over 46 hours every 14 days 2. Retifanlimab: IV at 500 mg on day 1 of every other cycle (Cycles 1, 3, 5, etc) 3.9-ING-41: IV at 9.3 mg/kg twice weekly (days 1, 3, 8 and 11) for the first 4 cycles, then weekly (days 1 and 8) thereafter |
| Cohort A: Personalized neoantigen DNA vaccine + retifanlimab | EXPERIMENTAL | * Cohort A will receive the personalized neoantigen DNA vaccine via electroporation mediated IM injection alone during the first two priming doses, then concurrently with retifanlimab during the subsequent boosting doses (Doses 3 through 6) * The personalized neoantigen DNA vaccine will be given once every 28 days for up to 6 doses. Retifanlimab is given at a fixed dose of 500 mg every 28 days. * Patients may receive up to 6 doses of personalized neoantigen DNA vaccine and up to 12 months total of retifanlimab |
| Cohort B: Personalized neoantigen DNA vaccine + retifanlimab | EXPERIMENTAL | * Cohort B will receive the personalized neoantigen DNA vaccine via electroporation mediated IM injection plus concurrent retifanlimab beginning with Dose 1 and continuing for a total of 6 doses. * The personalized neoantigen DNA vaccine will be given once every 28 days for up to 6 doses. Retifanlimab is given at a fixed dose of 500 mg every 28 days. * Patients may receive up to 6 doses of personalized neoantigen DNA vaccine and up to 12 months total of retifanlimab |
| Dose Escalation Cohort (Phase I): Epacadostat + SCRT + Chemotherapy + Surgery | EXPERIMENTAL | * Epacadostat at the designated dose level starting on the 1st day of radiation therapy and continuing throughout chemotherapy until the day of surgery. * Standard of care preoperative therapy will consist of a total of approximately 20-24 weeks of short-course pelvic radiation and chemotherapy: * Cycle 0 Days 1-7(Week 1): Short-course pelvic radiation therapy (SCRT), 5 fractions over 1 week * Cycle 0 Days 8-21 or 8-28 (Weeks 2-4): Treatment break for 2 to 3 weeks; for patients enrolled at Washington University and Dana Farber only, tumor biopsy will be obtained between the end of RT and prior to chemotherapy (target Days 14-28) * Cycles 1-6: (6) 21-day cycles of CAPOX for a total of 18 weeks. CAPOX is typically capecitabine at 1000 mg/m\^2 PO BID (days 1-14 of each cycle) and oxaliplatin 130 mg/m\^2 IV Q3W. * Surgery will follow approximately 4 to 6 weeks after completion of CAPOX |
| Phase II Treatment Cohort: Epacadostat + SCRT + Chemotherapy + Surgery | EXPERIMENTAL | * Epacadostat 400 mg BID 1st day of radiation therapy and continuing for \~28 days, until biopsy (with the exception of patients enrolling to dose expansion and starting on epacadostat with neoadjuvant chemotherapy prior to approval of post-sIRB A2) * Preoperative therapy approximately 20-24 weeks of chemoradiation: * Week 1: SCRT, typically 5 Gy x 5 fractions over 1 week, with epacadostat 400 mg BID starting on D1 of SCRT * Weeks 2-4: Epacadostat monotherapy 400 mg BID \& continued for a minimum of 21 days, until the day prior to chemotherapy * For patients enrolled at Washington University and Dana Farber Cancer Institute ONLY, tumor biopsy between the end of RT and prior to initiation of chemotherapy. Tumor biopsy target of between Days 15-28 * Weeks 3-6: 4-5 weeks after completion of SCRT \& after completion of approximately 21-35 days of epacadostat, SOC neoadjuvant chemotherapy of CAPOX or FOLFOX will be initiated * Surgery will occur approximately 4-6 weeks after chemotherapy |
| Phase II Biomarker Cohort: SCRT + Chemotherapy + Surgery | ACTIVE_COMPARATOR | Washington University and Dana Farber only: Patients enrolled to this cohort will not receive epacadostat. Patients will undergo standard of care preoperative therapy consisting of approximately 20 to 24 weeks of chemoradiation. All treatment will be administered in this cohort as per institutional standard. The expected schedule for these patients will consist of 1 week of short-course pelvic radiation therapy, followed by a treatment break, followed by neoadjuvant chemotherapy. Approximately 4 to 6 weeks after completion of neoadjuvant chemotherapy, patients may undergo surgery. Tumor biopsy may occur at screening and after completion of RT, prior to starting neoadjuvant chemotherapy. |
| INCMGA00012 | EXPERIMENTAL | Single-agent INCMGA00012. |
| INCB001158 75 mg | EXPERIMENTAL | Single-agent INCB001158. |
| INCB001158 100 mg | EXPERIMENTAL | Single-agent INCB001158. |
| INCMGA00012 + INCB001158 | EXPERIMENTAL | Combination of INCMGA00012 and INCB001158. |
| Group A | EXPERIMENTAL | INCMGA00012 with epacadostat. |
| Group B | EXPERIMENTAL | INCMGA00012 with INCB050465. |
| Treatment Group A | EXPERIMENTAL | Epacadostat + pembrolizumab + mFOLFOX6 (oxaliplatin, leucovorin, 5-fluorouracil) |
| Treatment Group B | EXPERIMENTAL | Epacadostat + pembrolizumab + gemcitabine and nab-paclitaxel |
| Treatment Group C | EXPERIMENTAL | Epacadostat + pembrolizumab + carboplatin and paclitaxel |
| Treatment Group D | EXPERIMENTAL | Epacadostat + pembrolizumab + pemetrexed and investigators choice of platinum agent |
| Treatment Group E | EXPERIMENTAL | Epacadostat + pembrolizumab + cyclophosphamide |
| Treatment Group F | EXPERIMENTAL | Epacadostat + pembrolizumab + gemcitabine and investigators choice of platinum agent |
| Treatment Group G | EXPERIMENTAL | Epacadostat + pembrolizumab + investigators choice of platinum agent and 5-fluorouracil |
| Dose Escalation-Q2W | EXPERIMENTAL | INCMGA00012 treatment once every 2 weeks. |
| Dose Escalation- Q3W | EXPERIMENTAL | INCMGA00012 treatment once every 3 weeks. |
| Dose Escalation- Q4W | EXPERIMENTAL | INCMGA00012 treatment once every 4 weeks. |
| Expansion Cohort | EXPERIMENTAL | INCMGA00012 treatment for locally advanced or metastatic solid tumors. |
| MEDI4736 + INCB024360 | EXPERIMENTAL | MEDI4736 at selected dose levels every 2 weeks + INCB024360 25 mg BID as starting dose, followed by dose escalations until MTD or PAD is identified |
| Phase 1 Part 1 Epacadostat 25mg BID +Nivolumab | EXPERIMENTAL | Epacadostat 25mg oral twice daily (BID) continuous daily dosing in combination with Nivolumab administered intravenously (IV) at 3mg/kg Q2W |
| Phase 1 Part 1 Epacadostat 50mg BID +Nivolumab | EXPERIMENTAL | Epacadostat 50mg oral twice daily (BID) continuous daily dosing in combination with Nivolumab administered intravenously (IV) at 3mg/kg Q2W |
| Phase 1 Part 1 Epacadostat 100mg BID +Nivolumab | EXPERIMENTAL | Epacadostat 100mg oral twice daily (BID) continuous daily dosing in combination with Nivolumab administered intravenously (IV) at 3mg/kg Q2W. |
| Phase 1 Part 1 Epacadostat 300mg BID +Nivolumab | EXPERIMENTAL | Epacadostat 300mg oral twice daily (BID) continuous daily dosing in combination with Nivolumab administered intravenously (IV) at 3mg/kg Q2W. |
| Phase 1 Part 2 Epacadostat 100mg BID +Nivolumab +5-FU/Platinum | EXPERIMENTAL | Epacadostat 100mg oral twice daily (BID) continuous daily dosing in combination with Nivolumab 360mg Q3W and 5-FU/Platinum( Carboplatin or Cisplatin+5-Fluorouracil) administered intravenously (IV). |
| Phase 1 Part 2 Epacadostat 100mg BID +Pemetrexed/Platinum | EXPERIMENTAL | Epacadostat 100mg oral twice daily (BID) continuous daily dosing in combination with Nivolumab 360 mg Q3W and Pemetrexed/Platinum (Carboplatin orCisplatin+Pemetrexed) administered intravenously (IV). |
| Phase 1 Part 2 Epacadostat 100mg BID +Paclitaxel/Platinum | EXPERIMENTAL | Epacadostat 100mg oral twice daily (BID) continuous daily dosing in combination with Nivolumab 360 mg Q3W and Paclitaxel/Platinum(Carboplatin+Cisplatin+Paclitaxel)administered intravenously (IV). |
| Phase 2 Epacadostat 100mg BID + Nivolumab | EXPERIMENTAL | Epacadostat 100mg oral twice daily (BID) continuous daily dosing in combination with Nivolumab 240mg Q2W or 480 mg Q4W based on tumor type administered intravenously (IV). |
| Phase 2 Epacadostat 300mg BID + Nivolumab | EXPERIMENTAL | Epacadostat 300mg oral twice daily (BID) continuous daily dosing in combination with Nivolumab 240mg Q2W administered intravenously (IV). |
| Phase 1: MK-3475 + INCB024360 | EXPERIMENTAL | Phase 1: MK-3475 + INCB024360 25 mg twice a day (BID) as starting dose, followed by dose escalations (Phase 1) until recommended phase 2 dose of INCB024360 is determined |
| Phase 2: MK-3475 + INCB024360 | EXPERIMENTAL | (recommended phase 2 dose) |
| INCB024360 | EXPERIMENTAL | - |
| Name | Type | Description |
|---|---|---|
| carboplatin | DRUG | carboplatin will be administered intravenous on Day 1 of each 28 day cycle |
| paclitaxel | DRUG | paclitaxel will be administered intravenous on Days 1,8, and 15 of each 28 day cycle |
| retifanlimab | DRUG | retifanlimab will be administered intravenous on Day 1 of each 28 day cycle |
| Placebo | DRUG | Placebo administered intravenously every 3 weeks on Day 1 of each cycle for up to 35 cycles. |
| Pemetrexed | DRUG | Pemetrexed administered intravenously every 3 weeks on Day 1 of each cycle. |
| Cisplatin | DRUG | Cisplatin administered intravenously every 3 weeks on Day 1 of each cycle for 4 cycles. |
| nab-Paclitaxel | DRUG | nab-Paclitaxel administered intravenously every 3 weeks on Days 1, 8, and 15 of each cycle for 4 cycles. |
| Pembrolizumab | DRUG | Pembrolizumab administered intravenously Day 1 of each cycle every 3 weeks. |
| Epacadostat | DRUG | Epacadostat administered orally twice daily. |
| Sunitinib | DRUG | Sunitinib 50 mg administered orally once daily; 4 weeks on, 2 weeks off for 6-wk cycle. |
| Pazopanib | DRUG | Pazopanib 800 mg administered orally once daily. |
| Cetuximab | DRUG | Cetuximab administered intravenously on Cycle 1 Day 1 followed by administration every week. |
| 5-Fluorouracil | DRUG | 5-Fluorouracil administered intravenously every 3 weeks for \</= 6 cycles. |
| Bevacizumab | DRUG | -The first infusion will be over the course of 90 minutes; if tolerated, the second infusion will be over the course of 60 minutes; if tolerated, all subsequent infusions will be over 30 minutes |
| Radiation therapy | RADIATION | -The gross tumor maximum diameter (to be irradiated) to be \</= 6 cm in the first 6 patients. If more than 1 target is irradiated, then the sum of all the target maximum diameters should be \</= 6 cm. No more than 3 separate targets for RT is allowed. |
| HPV ctDNA Response based radiation | RADIATION | Total radiation doses per response group: * Favorable response: 5040 cGy in 28 fractions * Intermediate response: 5400 cGy in 30 fractions * Unfavorable response: 6120 cGy in 34 fractions |
| Chemotherapy | DRUG | 1. Mitomycin-C(MMC) 12 mg/m2 on day 1 AND one of the following: 2. Capecitabine 825 mg/m2 twice daily on all days of radiotherapy for all response groups OR 5-Fluorouracil: 1000 mg/m²/day as a continuous infusion for 96 hours on days 1-4 and 29-32 |
| Biopsy | PROCEDURE | Undergo tumor biopsy |
| Biospecimen Collection | PROCEDURE | Undergo blood sample collection |
| Computed Tomography | PROCEDURE | Undergo CT/MRI |
| Magnetic Resonance Imaging | PROCEDURE | Undergo CT/MRI |
| Tuparstobart | DRUG | Given IV |
| Verzistobart | DRUG | Given IV |
| All-trans retinoic acid | DRUG | All-trans retinoic acid (ATRA) 45mg/m2 orally in two equally divided doses on days 1-14 of each 28-day cycle, continued until disease progression, unacceptable toxicity, or 2 years from the first dose of study medication, whichever occurs first. |
| INCAGN02385 | DRUG | INCAGN02385 350mg will be administered intravenously every 2 weeks. |
| INCAGN02390 | DRUG | INCAGN02390 400 mg will be administered intravenously every 2 weeks. |
| Capecitabine | DRUG | PO Capecitabine |
| Oxaliplatin | DRUG | IV Oxaliplatin |
| pemigatinib | DRUG | pemigatinib will be administered orally QD. |
| Pelareorep | BIOLOGICAL | Given IV |
| Quality-of-Life Assessment | OTHER | Ancillary studies |
| Questionnaire Administration | OTHER | Ancillary studies |
| INCMGA00012 | DRUG | 500mg IV neoadjuvant treatment; 500 mg adjuvant treatment |
| INCAGN01876 | DRUG | 300mg IV neoadjuvant treatment; 300 mg adjuvant treatment |
| SRS | DRUG | administered over the course of 3 consecutive business days (8 Gy x 3 fractions, one fraction per day, total dose 24 Gy). |
| Brain surgery | PROCEDURE | maximal safe surgical resection of the tumor. |
| Brigatinib | DRUG | Oral daily per predetermined dosage per protocol. |
| Neratinib | DRUG | Oral daily per predetermined dosage per protocol. |
| Platinum-based chemotherapy | DRUG | Investigator selected one of the following regimens: pemetrexed + cisplatin, pemetrexed + carboplatin, or paclitaxel + carboplatin, depending on histology. |
| DEC-205/NY-ESO-1 Fusion Protein CDX-1401 | BIOLOGICAL | Given via intracutaneous injection |
| Laboratory Biomarker Analysis | OTHER | Correlative studies |
| Pharmacological Study | OTHER | Correlative studies |
| Poly ICLC | DRUG | Given SC |
| 9-ING-41 | DRUG | a maleimide-based ATP-competitive and selective glycogen synthase kinase-3β (GSK-3β) inhibitor with an IC50 of 0.71 μM. 9-ING-41 significantly leads to cell cycle arrest, autophagy and apoptosis in cancer cells |
| Personalized Neoantigen DNA vaccine | BIOLOGICAL | The sites of immunization may be rotated for each of the immunizations. |
| TDS-IM v 2.0 electroporation device | DEVICE | Each DNA vaccination will be 1 mL vaccine administered intramuscularly using an integrated electroporation administration system |
| Short-course radiation therapy | RADIATION | Short-course pelvic radiation therapy, 5 Gy x 5 fractions over 1 week |
| CAPOX chemotherapy | DRUG | Standard of care |
| FOLFOX chemotherapy | DRUG | Standard of care |
| INCB001158 | DRUG | Part 1: INCB001158 75 or 100 mg twice daily administered orally. |
| Retifanlimab + INCB001158 | DRUG | Part 2: INCB001158 at the recommended Phase 2 dose selected from Part 1 in combination with INCMGA00012 . |
| INCB050465 | DRUG | Part 1: INCB050465 at the protocol-defined starting dose administered orally once daily, with dose escalation to determine the maximum tolerated dose. Part 2: INCB050465 at the recommended dose from Part 1. |
| Leucovorin | DRUG | Leucovorin |
| Gemcitabine | DRUG | Gemcitabine |
| Cyclophosphamide | DRUG | Cyclophosphamide |
| Investigator's choice of platinum agent | DRUG | Investigator's choice of platinum agent: carboplatin or cisplatin |
| MEDI4736 | DRUG | MEDI4736 administered intravenously (IV) every two weeks (q2w) |
| INCB024360 | DRUG | INCB024360: Oral daily dosing |
| Nivolumab | DRUG | specified dose and dosing schedule |
| MK-3475 | DRUG | IV infusion |
Inclusion Criteria: * Able to comprehend and willing to sign a written ICF for the study. * Are 18 years of age or older (or as applicable per local country requirements). * Histologically or cytologically verified, inoperable locally recurrent or metastatic SCAC. * No prior systemic therapy...
INCMGA00012 is an investigational monoclonal antibody being studied for glioblastoma, an aggressive brain cancer. It is being evaluated in patients with recurrent glioblastoma in combination with other treatments. It is not approved for any indication and remains in clinical development.
INCMGA00012 is being developed by Incyte Corporation, which trades on the Nasdaq under the ticker INCY. Incyte is the sponsor of the clinical program evaluating this monoclonal antibody in glioblastoma.
INCMGA00012 is in Phase 2 clinical development. The program consists of one active trial that is currently active but not recruiting. The drug is investigational and has not been approved by the FDA for any indication.
INCMGA00012 is being studied in the Phase 2 trial NCT04225039, titled Anti-GITR/Anti-PD1/Stereotactic Radiosurgery, in Recurrent Glioblastoma. The trial is active but not recruiting, is controlled, is not randomized or double blinded, and has enrolled 39 patients in the United States.
INCMGA00012 is also written as INCMGA00012. These refer to the same investigational monoclonal antibody being developed by Incyte Corporation for glioblastoma. Searches using either form point to the same drug candidate and the same clinical program.