INCMGA00012 in Combination With Chemoradiation in Participants With Stage III Non-Small Cell Lung Cancer (POD1UM-301)

A Randomized, Double-Blind, Placebo-Controlled Phase 3 Study of INCMGA00012, an Anti-PD-1 Antibody, in Combination With Chemoradiation in Participants With Unresectable, Stage III Non-Small Cell Lung Cancer (POD1UM-301)

The purpose of this study is to assess the efficacy and safety of INCMGA00012 in combination with chemoradiation therapy (CRT) in participants with unresectable, Stage III non-small cell lung cancer (NSCLC). The study will randomize approximately 360 participants in a 2:1 ratio into the INCMGA00012 in combination with CRT followed by consolidation therapy with INCMGA00012 treatment group and placebo in combination with CRT followed by consolidation therapy with placebo treatment group.

Study Overview

• Status: Withdrawn
• Conditions: Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: Retifanlimab; Drug: Pemetrexed; Drug: Cisplatin; Drug: Carboplatin; Drug: Paclitaxel; Drug: Etoposide; Radiation: Radiotherapy; Drug: Placebo

• Study Type: Interventional
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histologically or cytologically confirmed NSCLC that is locally advanced and unresectable.
• Adequate tumor sample from fresh biopsy or archival tissue block must be available.
• Evaluable 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 cancer treatment for this malignancy, including but not limited to radiation therapy, investigational agents, chemotherapy, and immunotherapy for disease under consideration.
• Recent major surgery within 4 weeks before entry into the study.
• Any medical contraindication to platinum-based doublet chemotherapy.
• Active autoimmune disease requiring systemic immunosuppression in excess of physiologic consolidation doses of corticosteroids (> 10 mg/day of prednisone or equivalent).
• Known hypersensitivity to another monoclonal antibody that cannot be controlled with standard measures (eg, antihistamines and corticosteroids).
• Mixed small cell and NSCLC histology.
• Evidence of interstitial lung disease or active noninfectious pneumonitis.
• Participants who are HIV-positive.
• History of organ transplant, including allogeneic stem cell transplantation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Chemoradiation therapy + INCMGA00012	Drug: Retifanlimab; INCMGA00012 administered intravenously every 3 weeks on Day 1 of each 21-day cycle for 4 cycles, followed by a consolidation part of INCMGA00012 administered intravenously on Day 1 of each 28-day cycle for up to12 cycles.; Other Names: INCMGA00012; Drug: Pemetrexed; Pemetrexed administered intravenously every 3 weeks on Day 1 of each cycle with either carboplatin or cisplatin (nonsquamous NSCLC only) for 2 cycles (if radiation therapy is started on Cycle 1 Day 1) or 3 cycles (if radiation therapy is started after Cycle 1).; Drug: Cisplatin; Cisplatin administered intravenously every 3 weeks on Day 1 of each cycle with either etoposide or pemetrexed (nonsquamous NSCLC only) for 2 cycles (if radiation therapy is started on Cycle 1 Day 1) or 3 cycles (if radiation therapy is started after Cycle 1).; Drug: Carboplatin; Carboplatin administered intravenously every 3 weeks on Day 1 of each cycle with either pemetrexed (nonsquamous NSCLC only) or paclitaxel for 2 cycles (if radiation therapy is started on Cycle 1 Day 1) or 3 cycles (if radiation therapy is started after Cycle 1).; Drug: Paclitaxel; Paclitaxel administered intravenously every 3 weeks on Days 1, 8, and 15 of each cycle with carboplatin for 2 cycles (if radiation therapy is started on Cycle 1 Day 1) or 3 cycles (if radiation therapy is started after Cycle 1).; Drug: Etoposide; Etoposide administered intravenously every 3 weeks on Days 1-3 of each cycle with cisplatin for 2 cycles (if radiation therapy is started on Cycle 1 Day 1) or 3 cycles (if radiation therapy is started after Cycle 1).; Radiation: Radiotherapy; Total dose of 60 Gy ± 10% (54 to 66 Gy) in 2 Gy daily fractions.
ACTIVE_COMPARATOR: Chemoradiation therapy + Placebo	Drug: Pemetrexed; Pemetrexed administered intravenously every 3 weeks on Day 1 of each cycle with either carboplatin or cisplatin (nonsquamous NSCLC only) for 2 cycles (if radiation therapy is started on Cycle 1 Day 1) or 3 cycles (if radiation therapy is started after Cycle 1).; Drug: Cisplatin; Cisplatin administered intravenously every 3 weeks on Day 1 of each cycle with either etoposide or pemetrexed (nonsquamous NSCLC only) for 2 cycles (if radiation therapy is started on Cycle 1 Day 1) or 3 cycles (if radiation therapy is started after Cycle 1).; Drug: Carboplatin; Carboplatin administered intravenously every 3 weeks on Day 1 of each cycle with either pemetrexed (nonsquamous NSCLC only) or paclitaxel for 2 cycles (if radiation therapy is started on Cycle 1 Day 1) or 3 cycles (if radiation therapy is started after Cycle 1).; Drug: Paclitaxel; Paclitaxel administered intravenously every 3 weeks on Days 1, 8, and 15 of each cycle with carboplatin for 2 cycles (if radiation therapy is started on Cycle 1 Day 1) or 3 cycles (if radiation therapy is started after Cycle 1).; Drug: Etoposide; Etoposide administered intravenously every 3 weeks on Days 1-3 of each cycle with cisplatin for 2 cycles (if radiation therapy is started on Cycle 1 Day 1) or 3 cycles (if radiation therapy is started after Cycle 1).; Radiation: Radiotherapy; Total dose of 60 Gy ± 10% (54 to 66 Gy) in 2 Gy daily fractions.; Drug: Placebo; Placebo administered intravenously every 3 weeks on Day 1 of each 21-day cycle for 4 cycles, followed by a consolidation part of placebo administered intravenously on Day 1 of each 28-day cycle for up to 12 cycles.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS)	Defined as the time from randomization until disease progression, per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) as determined by blinded independent central review (BICR), or death due to any cause.	Up to approximately 3 years.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS)	Defined as the time from randomization until death due to any cause.	Up to approximately 3 years.
Objective response rate (ORR)	Defined as the percentage of participants having a complete response or partial response per RECIST v1.1 based on BICR.	Up to approximately 3 years.
Duration of response (DOR)	Defined as the time from the first documented response (complete response or partial response) according to RECIST v1.1 until disease progression or death due to any cause.	Up to approximately 3 years.
Number of treatment-emergent adverse events	Defined as adverse events reported for the first time or worsening of a pre-existing event after first dose of study treatment.	Up to approximately 3 years.
Cmax of INCMGA00012.	Maximum observed plasma or serum concentration.	Cycle 1 Day 1, Cycle 2 Day 1 and Consolidation Cycle 1 Day 1, Cycle 4 Day 1, Cycle 8 Day 1, and Cycle 12 Day 1, up to approximately 18 months.
tmax of INCMGA00012.	Time to maximum concentration.	Cycle 1 Day 1, Cycle 2 Day 1 and Consolidation Cycle 1 Day 1, Cycle 4 Day 1, Cycle 8 Day 1, and Cycle 12 Day 1, up to approximately 18 months.
Cmin of INCMGA00012.	Minimum observed plasma or serum concentration over the dose interval.	Cycle 1 Day 1, Cycle 2 Day 1 and Consolidation Cycle 1 Day 1, Cycle 4 Day 1, Cycle 8 Day 1, and Cycle 12 Day 1, up to approximately 18 months.
AUC0-t of INCMGA00012.	Area under the plasma or serum concentration curve.	Cycle 1 Day 1, Cycle 2 Day 1 and Consolidation Cycle 1 Day 1, Cycle 4 Day 1, Cycle 8 Day 1, and Cycle 12 Day 1, up to approximately 18 months.

Collaborators and Investigators

• Sponsor: Incyte Corporation

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): July 31, 2020
• Primary Completion (ANTICIPATED): November 30, 2023
• Study Completion (ANTICIPATED): January 31, 2025

Study Registration Dates

• First Submitted: December 17, 2019
• First Submitted That Met QC Criteria: December 17, 2019
• First Posted (ACTUAL): December 18, 2019

Study Record Updates

• Last Update Posted (ACTUAL): June 9, 2020
• Last Update Submitted That Met QC Criteria: June 5, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: Non-small cell lung cancer; PD-1; PD-L1; Stage III; unresectable
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Folic Acid Antagonists; Carboplatin; Etoposide; Paclitaxel; Cisplatin; Pemetrexed
• Other Study ID Numbers: INCMGA 0012-301

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