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

A Phase 2 Study of INCMGA00012 (PD-1 Inhibitor) in Participants With Selected Solid Tumors (POD1UM-203)

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.

Study Overview

• Status: Completed
• Conditions: Metastatic Melanoma; Unresectable Melanoma; Metastatic Urothelial Cancer; Metastatic Non-small Cell Lung Cancer; Locally Advanced Renal Cell Carcinoma; Locally Advanced Urothelial Cancer; Metastatic Clear-Cell Renal Cell Carcinoma
• Intervention / Treatment: Drug: Retifanlimab

• Study Type: Interventional
• Enrollment (Actual): 121
• Phase: Phase 2

Contacts and Locations

Study Locations

• Austria
  • Graz, Austria
    • LKH Graz
  • Innsbruck, Austria, A-6020
    • Medizinische Universität Innsbruck
  • Linz, Austria, 4010
    • Ordensklinikum
  • St. Polten, Austria, 3100
    • Universitätsklinikum St. Pölten
• France
  • Bordeaux, France, 33076
    • Institut Bergonié
  • Marseille, France, 13009
    • Institut Paoli Calmettes
  • Marseille, France, 13885
    • CEPCM / CHU Timone
  • Paris, France, 75015
    • Georges Pompidou European Hospital
  • Strasbourg, France, 67091
    • Hopitaux Universitaires de Strasbourg
• Hungary
  • Miskolc, Hungary, 3526
    • BAZ County Hospital
  • Szolnok, Hungary, 5004
    • Hetenyi G Korhaz, Onkologiai Kozpont
• Italy
  • Ancona, Italy, 60126
    • Azienda Ospedaliera Universitaria Ospedali Riuniti di Ancona
  • Cremona, Italy, 26100
    • ASST Istituti Ospitalieri
  • Meldola, Italy, 47014
    • Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
  • Rome, Italy, 00144
    • Istituto Nazionale Tumori Regina Elena
  • Siena, Italy, 53100
    • Azienda Ospedaliera Universitaria Senese
• Poland
  • Lublin, Poland, 20-093
    • Specjalistyczna Praktyka Lekarska
  • Otwock, Poland, 05-400
    • Biovirtus Research Site
  • Mazowieckie
    • Warszawa, Mazowieckie, Poland
      • Centrum Onkologii- Instytut im Marii Skłodowskiej Curie
  • Wielkopolskie
    • Poznan, Wielkopolskie, Poland
      • Med-Polonia Sp. z o. o.
• Romania
  • Cluj-Napoca, Romania, 400461
    • Medisprof srl
  • Constanta, Romania, 900591
    • Clinical Emergency Hospital of Constanta
  • Iasi, Romania, 700106
    • Center of Oncology Euroclinic
  • Sibiu, Romania, 550245
    • Spitalul Clinic Judetean de Urgenta Sibiu
  • Timisoara, Romania, 300166
    • Oncocenter - Oncologie Clinica SRL
  • Dolj
    • Craiova, Dolj, Romania, 200347
      • Centrul de Oncologie Sfantul Nectarie
    • Craiova, Dolj, Romania, 200385
      • Oncolab SRL
• Spain
  • A Coruna, Spain, 08041
    • Centro Oncológico de Galicia
  • Barcelona, Spain, 08025
    • Hospital de La Santa Creu I Sant Pau
  • Barcelona, Spain, 08025
    • Hospital Universitario Vall d'Hebron
  • Madrid, Spain, 28033
    • MD Anderson Cancer Center Madrid
  • Majadahonda, Spain, 28220
    • Hospital Puerta de Hierro
  • Valencia, Spain, 46026
    • Hospital Universitari La Fe
  • Barcelona
    • Sabadell, Barcelona, Spain, 08208
      • Hospital Universitari Parc Tauli
• United States
  • California
    • Fresno, California, United States, 93720
      • California Cancer Associates For Research and Excellence
    • Fresno, California, United States, 93720
      • California Cancer Associates for Research and Excellence, Inc.
    • San Marcos, California, United States, 92069
      • California Cancer Associates for Research and Excellence, Inc.
    • Santa Rosa, California, United States, 95403
      • St Joseph Heritage Healthcare
    • Santa Rosa, California, United States, 95403
      • St. Joseph Health Medical Group - Annadel Medical Group
  • Colorado
    • Denver, Colorado, United States, 80218
      • Rocky Mountain Cancer Centers - Denver - Midtown
  • Delaware
    • Newark, Delaware, United States, 19718
      • Christiana Care Helen F. Graham Cancer Center
  • Maryland
    • Bethesda, Maryland, United States, 20817
      • Rcca Md, Llc
  • New Jersey
    • East Orange, New Jersey, United States, 07018
      • VA New Jersey Health Care System
  • New York
    • Albany, New York, United States, 12208
      • New York Oncology Hematology - Albany
  • Oregon
    • Portland, Oregon, United States, 97227
      • Kaiser Permanente
  • Texas
    • Austin, Texas, United States, 78731
      • Texas Oncology Surgical Specialists - Austin Central
    • Corpus Christi, Texas, United States, 78404
      • Coastal Bend Cancer Center
    • Plano, Texas, United States, 75093
      • AIM Trials, LLC
    • San Antonio, Texas, United States, 78217
      • Texas Oncology - San Antonio Northeast
    • The Woodlands, Texas, United States, 77380
      • Oncology and Hematology Associates of Southwest Virginia, Inc.
    • Waco, Texas, United States, 76712
      • Texas Oncology - Waco
  • Virginia
    • Wytheville, Virginia, United States, 24382
      • Oncology & Hematology Associates Of Southwest Virginia, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Melanoma: retifanlimab 500 mg; 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.	Drug: Retifanlimab; Retifanlimab administered intravenously at 500 mg every 4 weeks; Other Names: INCMGA00012
Experimental: NSCLC: retifanlimab 500 mg; 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.	Drug: Retifanlimab; Retifanlimab administered intravenously at 500 mg every 4 weeks; Other Names: INCMGA00012
Experimental: UC: retifanlimab 500 mg; 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.	Drug: Retifanlimab; Retifanlimab administered intravenously at 500 mg every 4 weeks; Other Names: INCMGA00012
Experimental: RCC: retifanlimab 500 mg; 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.	Drug: Retifanlimab; Retifanlimab administered intravenously at 500 mg every 4 weeks; Other Names: INCMGA00012

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	up to 25.9 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	up to 28.2 months
First-dose Cmax of Retifanlimab	Cmax was defined as the maximum observed plasma or serum concentration of retifanlimab.	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.	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.	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.	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.	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.	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.	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.	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)
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.	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.	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.	up to 25.9 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.	up to approximately 2.3 years

Collaborators and Investigators

• Sponsor: Incyte Corporation
• Investigators: Study Director: Mark Cornfeld, MD, Incyte Corporation

Study record dates

Study Major Dates

• Study Start (Actual): January 9, 2019
• Primary Completion (Actual): April 15, 2021
• Study Completion (Actual): June 28, 2022

Study Registration Dates

• First Submitted: September 19, 2018
• First Submitted That Met QC Criteria: September 19, 2018
• First Posted (Actual): September 20, 2018

Study Record Updates

• Last Update Posted (Actual): July 21, 2023
• Last Update Submitted That Met QC Criteria: July 13, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: non-small cell lung cancer; urothelial cancer; melanoma; renal cell carcinoma; PD-1inhibitor
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms by Histologic Type; Neoplasms; Lung Diseases; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Kidney Neoplasms; Lung Neoplasms; Neuroendocrine Tumors; Nevi and Melanomas; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Carcinoma, Renal Cell; Carcinoma, Non-Small-Cell Lung; Carcinoma; Melanoma
• Other Study ID Numbers: INCMGA 0012-203

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No