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

Metastatic Melanoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03679767
• Other study ID #: INCMGA 0012-203
• Status: Completed
• Phase: Phase 2
• Start date: January 9, 2019
• Est. completion date: June 28, 2022

Study information

• Verified date: July 2023
• Source: Incyte Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 121
• Est. completion date: June 28, 2022
• Est. primary completion date: April 15, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Non-Small-Cell Lung
• Carcinoma, Renal Cell
• Locally Advanced Renal Cell Carcinoma
• Locally Advanced Urothelial Cancer
• Melanoma
• Metastatic Clear-Cell Renal Cell Carcinoma
• Metastatic Melanoma
• Metastatic Non-small Cell Lung Cancer
• Metastatic Urothelial Cancer
• Unresectable Melanoma

Intervention

Drug:
• Retifanlimab
Retifanlimab administered intravenously at 500 mg every 4 weeks

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Incyte Corporation

Countries where clinical trial is conducted

United States,  Austria,  France,  Hungary,  Italy,  Poland,  Romania,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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)
Secondary	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
Secondary	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)
Secondary	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
Secondary	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)
Secondary	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
Secondary	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)