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

Phase 2

Completed

Conditions: Metastatic Non-small Cell Lung Cancer
Metastatic Melanoma
Locally Advanced Renal Cell Carcinoma
Locally Advanced Urothelial Cancer
Metastatic Urothelial Cancer
Unresectable Melanoma
Metastatic Clear-Cell Renal Cell Carcinoma

Interventions: Drug: Retifanlimab

Registration Number: NCT03679767

Lead Sponsor: Incyte Corporation

Brief Summary: The purpose of this study is to assess the clinical activity and safety of INCMGA00012 in participants with advanced solid tumors where the efficacy of PD-1 inhibitors has previously been established.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 121

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Melanoma: retifanlimab 500 mg	Retifanlimab	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	Retifanlimab	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.
RCC: retifanlimab 500 mg	Retifanlimab	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.
UC: retifanlimab 500 mg	Retifanlimab	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.

Primary Outcome Measures

Name	Time	Method
Overall Response Rate (ORR)	up to 25.9 months	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.

Secondary Outcome Measures

Name	Time	Method
First-dose Cmax of Retifanlimab	preinfusion and 10 minutes postinfusion (± 10 minutes) on Day 1 of Cycle 1	Cmax was defined as the maximum observed plasma or serum concentration of retifanlimab.
Disease Control Rate (DCR)	up to 25.9 months	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.
Duration of Response (DOR)	up to 24.0 months	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.
Tmax of Retifanlimab at Steady-state	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)	tmax was defined as the time to the maximum concentration of retifanlimab.
Cmax of Retifanlimab at Steady-state	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)	Cmax was defined as the maximum observed plasma or serum concentration of retifanlimab.
First-dose Cmin of Retifanlimab	preinfusion and 10 minutes postinfusion (± 10 minutes) on Day 1 of Cycle 1	Cmin was defined as the minimum observed plasma or serum concentration over the dose interval of retifanlimab.
Overall Survival	up to 28.2 months	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.
AUC0-t of Retifanlimab at Steady-state	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)	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.
Number of Participants With Treatment-emergent Adverse Events (TEAEs)	up to approximately 2.3 years	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.
First-dose Tmax of Retifanlimab	preinfusion and 10 minutes postinfusion (± 10 minutes) on Day 1 of Cycle 1	tmax was defined as the time to the maximum concentration of retifanlimab.
First-dose AUC0-t of Retifanlimab	preinfusion and 10 minutes postinfusion (± 10 minutes) on Day 1 of Cycle 1	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.
Progression-free Survival (PFS)	up to 25.9 months	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.
Cmin of Retifanlimabv at Steady-state	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)	Cmin was defined as the minimum observed plasma or serum concentration over the dose interval of retifanlimab.

Trial Locations

Locations (51): Texas Oncology - Waco
🇺🇸
Waco, Texas, United States
LKH Graz
🇦🇹
Graz, Austria
California Cancer Associates for Research and Excellence, Inc.
🇺🇸
San Marcos, California, United States
CEPCM / CHU Timone
🇫🇷
Marseille, France
Christiana Care Helen F. Graham Cancer Center
🇺🇸
Newark, Delaware, United States
California Cancer Associates for Research and Excellence
🇺🇸
Fresno, California, United States
Coastal Bend Cancer Center
🇺🇸
Corpus Christi, Texas, United States
Oncology and Hematology Associates of Southwest Virginia, Inc.
🇺🇸
The Woodlands, Texas, United States
Rocky Mountain Cancer Centers - Denver - Midtown
🇺🇸
Denver, Colorado, United States
Kaiser Permanente
🇺🇸
Portland, Oregon, United States
Rcca Md, Llc
🇺🇸
Bethesda, Maryland, United States
St Joseph Heritage Healthcare
🇺🇸
Santa Rosa, California, United States
St. Joseph Health Medical Group - Annadel Medical Group
🇺🇸
Santa Rosa, California, United States
VA New Jersey Health Care System
🇺🇸
East Orange, New Jersey, United States
New York Oncology Hematology - Albany
🇺🇸
Albany, New York, United States
Texas Oncology Surgical Specialists - Austin Central
🇺🇸
Austin, Texas, United States
AIM Trials, LLC
🇺🇸
Plano, Texas, United States
Texas Oncology - San Antonio Northeast
🇺🇸
San Antonio, Texas, United States
Oncology & Hematology Associates of Southwest Virginia, Inc.
🇺🇸
Wytheville, Virginia, United States
Medizinische Universitat Innsbruck
🇦🇹
Innsbruck, Austria
Ordensklinikum
🇦🇹
Linz, Austria
Universitatsklinikum St. Polten
🇦🇹
St. Polten, Austria
Institut Bergonié
🇫🇷
Bordeaux, France
Institut Paoli Calmettes
🇫🇷
Marseille, France
Georges Pompidou European Hospital
🇫🇷
Paris, France
Hopitaux Universitaires De Strasbourg
🇫🇷
Strasbourg, France
Hetenyi G Korhaz, Onkologiai Kozpont
🇭🇺
Szolnok, Hungary
BAZ County Hospital
🇭🇺
Miskolc, Hungary
Azienda Ospedaliera Universitaria Ospedali Riuniti di Ancona
🇮🇹
Ancona, Italy
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
🇮🇹
Meldola, Italy
Istituto Nazionale Tumori Regina Elena
🇮🇹
Rome, Italy
ASST Istituti Ospitalieri
🇮🇹
Cremona, Italy
Azienda Ospedaliera Universitaria Senese
🇮🇹
Siena, Italy
Centrum Onkologii- Instytut im Marii Skłodowskiej Curie
🇵🇱
Warszawa, Mazowieckie, Poland
Med-Polonia Sp. z o. o.
🇵🇱
Poznan, Wielkopolskie, Poland
Specjalistyczna Praktyka Lekarska
🇵🇱
Lublin, Poland
BioVirtus Research Site
🇵🇱
Otwock, Poland
Centrul de Oncologie Sfantul Nectarie
🇷🇴
Craiova, Dolj, Romania
Oncolab SRL
🇷🇴
Craiova, Dolj, Romania
Medisprof SRL
🇷🇴
Cluj-Napoca, Romania
Clinical Emergency Hospital of Constanta
🇷🇴
Constanta, Romania
Center of Oncology Euroclinic
🇷🇴
Iasi, Romania
Spitalul Clinic Judetean de Urgenta Sibiu
🇷🇴
Sibiu, Romania
Oncocenter - Oncologie Clinica SRL
🇷🇴
Timisoara, Romania
Hospital Universitari Parc Tauli
🇪🇸
Sabadell, Barcelona, Spain
Hospital de la Santa Creu i Sant Pau
🇪🇸
Barcelona, Spain
Centro Oncologico De Galicia
🇪🇸
A Coruna, Spain
MD Anderson Cancer Center Madrid
🇪🇸
Madrid, Spain
Hospital Universitario Vall d'Hebron
🇪🇸
Barcelona, Spain
Hospital Puerta De Hierro
🇪🇸
Majadahonda, Spain
Hospital Universitari La Fe
🇪🇸
Valencia, Spain