A Study of INCAGN01876 in Participants With Advanced or Metastatic Solid Tumors

Study Overview
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Brief Summary
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This was an open-label, non-randomized Phase 1/2 safety study of INCAGN01876 in participants with advanced or metastatic solid tumors that was conducted in 2 parts. Part 1 is dose escalation and safety expansion which determines the optimal dose and maximum number of tolerated doses. Part 2 is dose expansion in which Part 1 recommended dose will be evaluated.

Official Title
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A Phase 1/2, Open-Label, Dose-Escalation, Safety and Tolerability Study of INCAGN01876 in Subjects With Advanced or Metastatic Solid Tumors

Conditions
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Advanced Malignancies, Metastatic Cancer

Intervention / Treatment
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* Drug: INCAGN01876


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Locally advanced or metastatic disease; locally advanced disease must not be amenable to resection with curative intent. Part 1: Participants with advanced or metastatic solid tumors. Part 2: Participants with advanced or metastatic adenocarcinoma of endometrium, melanoma, non-small cell lung cancer, and renal cell carcinoma. Participants who have disease progression after treatment with available therapies that are known to confer clinical benefit, or who are intolerant to treatment, or participants who refuse standard treatment. Presence of measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1. Exclusion Criteria: Laboratory and medical history parameters not within the protocol-defined range. Receipt of anticancer medications or investigational drugs within protocol-defined intervals before the first administration of study drug. Has not recovered to ≤ Grade 1 from toxic effects of prior therapy and/or complications from prior surgical intervention before starting therapy. Receipt of a live vaccine within 30 days of planned start of study therapy. Active autoimmune disease. Prior treatment with any tumor necrosis factor super family agonist. Known active central nervous system metastases and/or carcinomatous meningitis. Evidence of active, non-infectious pneumonitis or history of interstitial lung disease. Evidence of hepatitis B virus or hepatitis C virus infection or risk of reactivation.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase 1: 20.0 Milligram Per Kilograms (mg/kg) Every 2 Weeks (Q2W)<br>Participants received IV infusion of study drug at a dose of 20.0 mg/kg every Q2W starting on Day 1 of each cycle for up to 15 months. | Drug: INCAGN01876<br>* Initial cohort dose of INCAGN01876 monotherapy at the protocol-defined starting dose, with subsequent cohort escalations based on protocol-specific criteria. The recommended dose will be taken forward into expansion cohorts.<br>|
| Experimental: Phase 1: 0.03 mg/kg Q2W<br>Participants received intravenous (IV) infusion of study drug at a dose of 0.03 mg/kg every Q2W starting on Day 1 of each cycle for up to 15 months. | Drug: INCAGN01876<br>* Initial cohort dose of INCAGN01876 monotherapy at the protocol-defined starting dose, with subsequent cohort escalations based on protocol-specific criteria. The recommended dose will be taken forward into expansion cohorts.<br>|
| Experimental: Phase 1: 0.1 mg/kg Q2W<br>Participants received IV infusion of study drug at a dose of 0.1 mg/kg every Q2W starting on Day 1 of each cycle for up to 15 months. | Drug: INCAGN01876<br>* Initial cohort dose of INCAGN01876 monotherapy at the protocol-defined starting dose, with subsequent cohort escalations based on protocol-specific criteria. The recommended dose will be taken forward into expansion cohorts.<br>|
| Experimental: Phase 1: 0.3 mg/kg Q2W<br>Participants received IV infusion of study drug at a dose of 0.3 mg/kg every Q2W starting on Day 1 of each cycle for up to 15 months. | Drug: INCAGN01876<br>* Initial cohort dose of INCAGN01876 monotherapy at the protocol-defined starting dose, with subsequent cohort escalations based on protocol-specific criteria. The recommended dose will be taken forward into expansion cohorts.<br>|
| Experimental: Phase 1: 1.0 mg/kg Q2W<br>Participants received IV infusion of study drug at a dose of 1.0 mg/kg every Q2W starting on Day 1 of each cycle for up to 15 months. | Drug: INCAGN01876<br>* Initial cohort dose of INCAGN01876 monotherapy at the protocol-defined starting dose, with subsequent cohort escalations based on protocol-specific criteria. The recommended dose will be taken forward into expansion cohorts.<br>|
| Experimental: Phase 1: 3.0 mg/kg Q2W<br>Participants received IV infusion of study drug at a dose of 3.0 mg/kg every Q2W starting on Day 1 of each cycle for up to 15 months. | Drug: INCAGN01876<br>* Initial cohort dose of INCAGN01876 monotherapy at the protocol-defined starting dose, with subsequent cohort escalations based on protocol-specific criteria. The recommended dose will be taken forward into expansion cohorts.<br>|
| Experimental: Phase 1: 5.0 mg/kg Q2W<br>Participants received IV infusion of study drug at a dose of 5.0 mg/kg every Q2W starting on Day 1 of each cycle for up to 15 months. | Drug: INCAGN01876<br>* Initial cohort dose of INCAGN01876 monotherapy at the protocol-defined starting dose, with subsequent cohort escalations based on protocol-specific criteria. The recommended dose will be taken forward into expansion cohorts.<br>|
| Experimental: Phase 1: 10.0 mg/kg Q2W<br>Participants received IV infusion of study drug at a dose of 10.0 mg/kg every Q2W starting on Day 1 of each cycle for up to 15 months. | Drug: INCAGN01876<br>* Initial cohort dose of INCAGN01876 monotherapy at the protocol-defined starting dose, with subsequent cohort escalations based on protocol-specific criteria. The recommended dose will be taken forward into expansion cohorts.<br>|
| Experimental: Phase 1: 400 mg/kg Every 4 Weeks (Q4W)<br>Participants received IV infusion of study drug at a dose of 400 mg/kg every Q2W starting on Day 1 of each cycle for up to 15 months. | Drug: INCAGN01876<br>* Initial cohort dose of INCAGN01876 monotherapy at the protocol-defined starting dose, with subsequent cohort escalations based on protocol-specific criteria. The recommended dose will be taken forward into expansion cohorts.<br>|
| Experimental: Phase 2: 300 mg/kg Q2W<br>Participants received IV infusion of study drug at a dose of 300 mg/kg every Q2W starting on Day 1 of each cycle for up to 15 months. | Drug: INCAGN01876<br>* Initial cohort dose of INCAGN01876 monotherapy at the protocol-defined starting dose, with subsequent cohort escalations based on protocol-specific criteria. The recommended dose will be taken forward into expansion cohorts.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Any Treatment-Emergent Adverse Event (TEAE) and as Per the Severity | AE is defined as any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. A treatment-emergent AE is any AE either reported for first time or worsening of a pre-existing event after the first dose of study drug. Grade 1 AEs is defined as Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 AEs is defined as Moderate; minimal, local, or non-invasive intervention indicated; limiting age-appropriate activities of daily living. Grade 3 AEs is defined as the severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living and Grade 4 AEs as life-threatening consequences; urgent intervention indicated. Data is reported for Grade 3 and higher severity for this outcome measure. | From screening through 60 days after end of treatment, up to Month 15 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Plasma Concentration (Cmax) |  | Day 1 of Cycles 1 and 6 post-dose | 
| Time to Maximum Concentration (Tmax) |  | Day 1 of Cycles 1 and 6 post-dose | 
| Minimum Observed Plasma Concentration Over the Dose Interval (Cmin) |  | Day 1 of Cycles 2, 3, 4, 6, and 7 post-dose | 
| Area Under the Plasma Time Curve From Time = 0 to the Last Measurable Concentration (AUC0-t) |  | Day 1 of Cycles 1 and 6 post-dose | 
| Objective Response Rate (ORR) Per RECIST v1.1 and Modified RECISTv1.1 (mRECIST) | ORR is defined as the percentage of participants having complete response (CR) or partial response (PR), as determined by investigator assessment of radiographic disease assessments. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm. | Baseline and every 8 weeks for the first 12 months and then every 12 weeks thereafter up to 15 months | 
| Duration of Response (DOR) Per RECIST and mRECIST | DOR is defined as the time from earliest date of disease response (CR or PR) until earliest date of disease progression, as determined by investigator assessment of radiographic disease assessments per RECIST v1.1 and mRECIST, or death due to any cause if occurring sooner than progression. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm. | Baseline and every 8 weeks for the first 12 months and then every 12 weeks thereafter up to 15 months | 
| Duration of Disease Control Per RECIST and mRECIST | Duration of disease control (CR, PR, and stable disease [SD]), as measured from first report of SD or better until disease progression, as determined by investigator assessment of radiographic disease assessments per RECIST v1.1 and mRECIST, or death due to any cause if occurring sooner than progression. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm. Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started. | Baseline and every 8 weeks for the first 12 months and then every 12 weeks thereafter up to 15 months | 
| Progression Free Survival (PFS) Per RECIST and mRECIST | PFS is defined as the time from date of first dose of study drug until the earliest date of disease progression, as determined by investigator assessment of objective radiographic disease assessments per RECIST v1.1 and mRECIST, or death due to any cause if occurring sooner than progression. Progression is defined by RECIST and mRECIST as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study and an absolute lesion increase of at least 5 mm or the appearance of new lesions. | Baseline and every 8 weeks for the first 12 months and then every 12 weeks thereafter up to 15 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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glucocorticoid-induced tumor necrosis factor receptor (GITR), Solid tumor, adenocarcinoma of the endometrium, melanoma, non-small cell lung cancer (NSCLC), renal cell carcinoma (RCC)