NCT03679767 - A Study of INCMGA00012 in Participants With Selected Solid Tumors (POD1UM-203) | Crick

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Confirmed diagnosis of one of the following: treatment-naïve metastatic non-small cell lung cancer with high PD-L1 expression (tumor proportion score ≥ 50%) and no epidermal growth factor receptor (EGFR), alkaline phosphatase (ALK), or ROS activating genomic tumor aberrations; locally advanced or metastatic urothelial carcinoma in participants who are not eligible for cisplatin therapy and whose tumors express PD-L1 with a combined positive score ≥ 10; unresectable or metastatic melanoma; locally advanced or metastatic renal cell carcinoma with clear cell component (with or without sarcomatoid features) and having received no prior systemic therapy. * Measurable disease per RECIST v1.1. * Eastern Cooperative Oncology Group performance status 0 to 1. * Willingness to avoid pregnancy or fathering children. Exclusion Criteria: * Receipt of anticancer therapy or participation in another interventional clinical study within 21 days before the first administration of study drug. * Prior treatment with PD-1 or PD-L1 directed therapy (other immunotherapies may be acceptable with prior approval from the medical monitor). * Radiotherapy within 14 days of first dose of study treatment with the following caveats: 28 days for pelvic radiotherapy; 6 months for thoracic region radiotherapy that is \> 30 Gy. * Toxicity of prior therapy that has not recovered to ≤ Grade 1 or baseline (with the exception of anemia not requiring transfusion support and any grade of alopecia). Endocrinopathy, if well-managed, is not exclusionary and should be discussed with sponsor medical monitor. * Has not recovered adequately from toxicities and/or complications from surgical intervention before starting study drug. * Laboratory values outside the protocol-defined range at screening. * Known additional malignancy that is progressing or requires active treatment, or history of other malignancy within 3 years of study entry. * Active autoimmune disease requiring systemic immunosuppression in excess of physiologic maintenance doses of corticosteroids (\> 10 mg of prednisone or equivalent). * Evidence of interstitial lung disease or active noninfectious pneumonitis. * Known active central nervous system metastases and/or carcinomatous meningitis. * Known active hepatitis B antigen, hepatitis B virus, or hepatitis C virus infection. * Active infections requiring systemic therapy. * Known to be HIV-positive, unless all of the following criteria are met: CD4+ count ≥ 300/μL, undetectable viral load, receiving antiretroviral therapy. * Known hypersensitivity to another monoclonal antibody that cannot be controlled with standard measures (eg, antihistamines and corticosteroids). * Impaired cardiac function or clinically significant cardiac disease. * Is pregnant or breastfeeding. * Has received a live vaccine within 28 days of the planned start of study drug.

Outcomes

Primary Outcomes

Overall Response Rate (ORR)

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.

Time frame: up to 25.9 months

Secondary Outcomes

Duration of Response (DOR)

DOR was defined as the time from initial objective response (CR or PR) per RECIST v1.1 until the first observation of documented disease progression (PD), as determined by the investigator, or death due to any cause. 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 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. PD: progression of a target or non-target lesion or presence of a new lesion.

Time frame: up to 24.0 months

Disease Control Rate (DCR)

DCR was defined as the proportion of participants with an overall response of CR, PR, or stable disease (SD), per RECIST v1.1. 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 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. PD: progression of a target or non-target lesion or presence of a new lesion. SD: no change in target lesions to qualify for CR, PR, or PD.

Time frame: up to 25.9 months

Progression-free Survival (PFS)

According to RECIST 1.1, PFS was defined as the length of time from the initial infusion of study drug until the earliest date of disease progression, determined by investigator assessment, or death due to any cause, if occurring sooner than progression.

Time frame: up to 25.9 months

Overall Survival

Overall survival was defined as the time in months between the first dose date (Day 1) and the date of death due to any cause.

Time frame: up to 28.2 months

Number of Participants With Treatment-emergent Adverse Events (TEAEs)

An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug-related. An AE could therefore have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study drug. A TEAE was defined as any AE either reported for the first time or the worsening of a pre-existing event after the first dose of retifanlimab and until the earlier of 90 days of the last administration of retifanlimab and new anti-cancer therapy start if any, are reported.

Time frame: up to approximately 2.3 years

First-dose Cmax of Retifanlimab

Cmax was defined as the maximum observed plasma or serum concentration of retifanlimab.

Time frame: preinfusion and 10 minutes postinfusion (± 10 minutes) on Day 1 of Cycle 1

Cmax of Retifanlimab at Steady-state

Cmax was defined as the maximum observed plasma or serum concentration of retifanlimab.

Time frame: preinfusion and 10 minutes postinfusion (± 10 minutes) on Day 1 of Cycles 1, 2, 4, and 6 (up to approximately 168 days; each cycle was 28 days)

First-dose Tmax of Retifanlimab

tmax was defined as the time to the maximum concentration of retifanlimab.

Time frame: preinfusion and 10 minutes postinfusion (± 10 minutes) on Day 1 of Cycle 1

Tmax of Retifanlimab at Steady-state

tmax was defined as the time to the maximum concentration of retifanlimab.

Time frame: preinfusion and 10 minutes postinfusion (± 10 minutes) on Day 1 of Cycles 1, 2, 4, and 6 (up to approximately 168 days; each cycle was 28 days)

First-dose Cmin of Retifanlimab

Cmin was defined as the minimum observed plasma or serum concentration over the dose interval of retifanlimab.

Time frame: preinfusion and 10 minutes postinfusion (± 10 minutes) on Day 1 of Cycle 1

Cmin of Retifanlimabv at Steady-state

Cmin was defined as the minimum observed plasma or serum concentration over the dose interval of retifanlimab.

Time frame: preinfusion and 10 minutes postinfusion (± 10 minutes) on Day 1 of Cycles 1, 2, 4, and 6 (up to approximately 168 days; each cycle was 28 days)

First-dose AUC0-t of Retifanlimab

AUC0-t was defined as the area under the plasma or serum concentration-time curve from time = 0 to the last measurable concentration at time = t of retifanlimab.

Time frame: preinfusion and 10 minutes postinfusion (± 10 minutes) on Day 1 of Cycle 1

AUC0-t of Retifanlimab at Steady-state

AUC0-t was defined as the area under the plasma or serum concentration-time curve from time = 0 to the last measurable concentration at time = t of retifanlimab.

Time frame: preinfusion and 10 minutes postinfusion (± 10 minutes) on Day 1 of Cycles 1, 2, 4, and 6 (up to approximately 168 days; each cycle was 28 days)

A Study of INCMGA00012 in Participants With Selected Solid Tumors (POD1UM-203)

Overview

Conditions

Interventions

Eligibility

Locations (52)

Outcomes

Primary Outcomes

Secondary Outcomes