Platinum-Based Chemotherapy With/Without INCMGA00012, an Anti-PD-1 Antibody, in Non-Small Cell Lung Cancer
- Conditions
- Metastatic Squamous Non-Small Cell Lung CancerMetastatic Nonsquamous Non-Small Cell Lung Cancer
- Interventions
- Registration Number
- NCT04205812
- Lead Sponsor
- Incyte Corporation
- Brief Summary
The purpose of this study is to assess the efficacy and safety of platinum-based chemotherapy with or without INCMGA00012 in participants with metastatic squamous and nonsquamous non-small cell lung cancer (NSCLC).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 583
- Histologically or cytologically confirmed NSCLC (either nonsquamous or squamous) that is Stage IV (AJCC v8).
- No prior systemic treatment for the advanced/metastatic NSCLC
- Able to provide a formalin-fixed archival tumor tissue sample during screening, or a fresh tumor biopsy
- Measurable disease per RECIST v1.1.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Life expectancy of at least 3 months.
- Willingness to avoid pregnancy or fathering children.
- Adequate organ function as indicated by protocol-specified laboratory values. - Has been fully vaccinated against SARS-CoV-2 or is willing and able to be fully vaccinated against SARS-CoV-2 during the study by starting the vaccination process during screening.
- Clinically significant cardiac disease within 6 months of start of study treatment.
- Any major surgery within 3 weeks of the first dose of study treatment.
- Thoracic radiation therapy of > 30 Gy within 6 months of the first dose of study treatment.
- History of peripheral neuropathy ≥ Grade 2 CTCAE v5 for participants who may receive cisplatin, paclitaxel, or nab-paclitaxel.
- Untreated central nervous system metastases and/or carcinomatous meningitis.
- Evidence or history of interstitial lung disease or noninfectious pneumonitis that required systemic steroids.
- Active infection requiring systemic therapy or active tuberculosis. Note: If required by country or local regulations to be tested for COVID-19 during screening, a participant should be excluded if they have a positive test result for SARS CoV-2 infection until both the retesting result is negative and clinical recovery is obtained.
- Superficial bladder cancer, squamous cell carcinoma of the skin, in situ cervical cancer, or other in situ cancers.
- Has contraindications to chemotherapy agents used in the study.
- Has an active autoimmune disease that has required systemic treatment in past 2 years.
- Is receiving systemic antibiotics or steroid therapy ≤ 7 days prior to the first dose of study treatment.
- Has received a live vaccine within 30 days before the first dose of study treatment (and until 90 days after last dose of study drug).
Note: While based on approved SARS-CoV-2 vaccines available worldwide, many vaccines are not live (mRNA and adenovirus vaccines do not contain live virus), if a live vaccine against SARS-CoV-2 is the only available option, prior consultation with the medical monitor should be obtained.
• Has known active HBV or HCV (testing must be performed to determine eligibility)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description INCMGA00012 + chemotherapy (nonsquamous NSCLC) Retifanlimab INCMGA00012 with pemetrexed + cisplatin OR carboplatin followed by INCMGA00012 plus pemetrexed until progression. INCMGA00012 + chemotherapy (nonsquamous NSCLC) Pemetrexed INCMGA00012 with pemetrexed + cisplatin OR carboplatin followed by INCMGA00012 plus pemetrexed until progression. INCMGA00012 + chemotherapy (nonsquamous NSCLC) Cisplatin INCMGA00012 with pemetrexed + cisplatin OR carboplatin followed by INCMGA00012 plus pemetrexed until progression. INCMGA00012 + chemotherapy (nonsquamous NSCLC) Carboplatin INCMGA00012 with pemetrexed + cisplatin OR carboplatin followed by INCMGA00012 plus pemetrexed until progression. Placebo + chemotherapy (nonsquamous NSCLC) Placebo Placebo with pemetrexed + cisplatin OR carboplatin followed by placebo plus pemetrexed until progression. Participants assigned to placebo + chemotherapy will have the option of receiving open-label monotherapy INCMGA00012 in a crossover period after documentation of progressive disease. Placebo + chemotherapy (nonsquamous NSCLC) Pemetrexed Placebo with pemetrexed + cisplatin OR carboplatin followed by placebo plus pemetrexed until progression. Participants assigned to placebo + chemotherapy will have the option of receiving open-label monotherapy INCMGA00012 in a crossover period after documentation of progressive disease. Placebo + chemotherapy (nonsquamous NSCLC) Cisplatin Placebo with pemetrexed + cisplatin OR carboplatin followed by placebo plus pemetrexed until progression. Participants assigned to placebo + chemotherapy will have the option of receiving open-label monotherapy INCMGA00012 in a crossover period after documentation of progressive disease. INCMGA00012 + chemotherapy (squamous NSCLC) Paclitaxel INCMGA00012 with carboplatin + paclitaxel OR nab-paclitaxel followed by INCMGA00012 until progression. INCMGA00012 + chemotherapy (squamous NSCLC) nab-Paclitaxel INCMGA00012 with carboplatin + paclitaxel OR nab-paclitaxel followed by INCMGA00012 until progression. Placebo + chemotherapy (squamous NSCLC) Placebo Placebo with carboplatin + paclitaxel OR nab-paclitaxel followed by placebo until progression. Participants assigned to placebo + chemotherapy will have the option of receiving open-label monotherapy INCMGA00012 in a crossover period after documentation of progressive disease. Placebo + chemotherapy (squamous NSCLC) nab-Paclitaxel Placebo with carboplatin + paclitaxel OR nab-paclitaxel followed by placebo until progression. Participants assigned to placebo + chemotherapy will have the option of receiving open-label monotherapy INCMGA00012 in a crossover period after documentation of progressive disease. Placebo + chemotherapy (nonsquamous NSCLC) Carboplatin Placebo with pemetrexed + cisplatin OR carboplatin followed by placebo plus pemetrexed until progression. Participants assigned to placebo + chemotherapy will have the option of receiving open-label monotherapy INCMGA00012 in a crossover period after documentation of progressive disease. INCMGA00012 + chemotherapy (squamous NSCLC) Retifanlimab INCMGA00012 with carboplatin + paclitaxel OR nab-paclitaxel followed by INCMGA00012 until progression. INCMGA00012 + chemotherapy (squamous NSCLC) Carboplatin INCMGA00012 with carboplatin + paclitaxel OR nab-paclitaxel followed by INCMGA00012 until progression. Placebo + chemotherapy (squamous NSCLC) Carboplatin Placebo with carboplatin + paclitaxel OR nab-paclitaxel followed by placebo until progression. Participants assigned to placebo + chemotherapy will have the option of receiving open-label monotherapy INCMGA00012 in a crossover period after documentation of progressive disease. Placebo + chemotherapy (squamous NSCLC) Paclitaxel Placebo with carboplatin + paclitaxel OR nab-paclitaxel followed by placebo until progression. Participants assigned to placebo + chemotherapy will have the option of receiving open-label monotherapy INCMGA00012 in a crossover period after documentation of progressive disease.
- Primary Outcome Measures
Name Time Method Overall Survival up to 39.1 months Overall survival was defined as the time between the date of randomization and the date of death due to any cause.
- Secondary Outcome Measures
Name Time Method Progression-free Survival (PFS) up to 35.8 months PFS was defined as the length of time from the date of randomization until the earliest date of disease progression by 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, if occurring sooner than progression.
Objective Response Rate up to 35.78 months Objective response rate was defined as the percentage of participants who had a confirmed complete response (CR) or partial response (PR) per RECIST v1.1 based on BICR at any post-Baseline visit until the first progressive disease or new anticancer therapy. 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.
Duration of Response up to 34.3 months Duration of response was defined as the time from the earliest date of documented response until the earliest date of disease progression or death from any cause, whichever comes first, per RECIST v1.1 based on BICR. 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.
Number of Participants With Any Treatment-emergent Adverse Event (TEAE) in the Randomized Treatment Period up to approximately 39 months 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 treatment. TEAEs were defined as any AEs either reported for the first time or the worsening of pre-existing events after the first dose of retifanlimab/placebo and within 90 days of the last administration of the randomized period. AEs that occurred after new anticancer therapy (including monotherapy treatment) were to be excluded.
Number of Participants Who Discontinued Study Drug Due to TEAEs in the Randomized Treatment Period up to approximately 39 months An 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 treatment. TEAEs were defined as any AEs either reported for the first time or the worsening of pre-existing events after the first dose of retifanlimab/placebo and within 90 days of the last administration of the randomized period. AEs that occurred after new anticancer therapy (including monotherapy treatment) were to be excluded.
Number of Participants With Any TEAE in the Monotherapy Treatment Period up to approximately 27 months An 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 treatment. TEAEs were defined as any AEs either reported for the first time or the worsening of pre-existing events after the first dose of retifanlimab/placebo and within 90 days of the last administration of the randomized period. AEs that occurred after new anticancer therapy (including monotherapy treatment) were to be excluded.
Number of Participants Who Discontinued Study Drug Due to TEAEs in the Monotherapy Treatment Period up to approximately 27 months An 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 treatment. TEAEs were defined as any AEs either reported for the first time or the worsening of pre-existing events after the first dose of retifanlimab/placebo and within 90 days of the last administration of the randomized period. AEs that occurred after new anticancer therapy (including monotherapy treatment) were to be excluded.
Cmax of Retifanlimab Cycle 1 Day 1: predose and end of infusion (EOI). Cycle 2 Day 1: predose. Cycle 4 Day 1: predose and EOI. Cycles 6, 8, and beyond Day 1: predose (every 4 cycles thereafter) and end of treatment visit or 30-day safety follow-up visit Cmax was defined as the maximum observed plasma concentration of retifanlimab
AUC of Retifanlimab Cycle 1 Day 1: predose and end of infusion (EOI). Cycle 2 Day 1: predose. Cycle 4 Day 1: predose and EOI. Cycles 6, 8, and beyond Day 1: predose (every 4 cycles thereafter) and end of treatment visit or 30-day safety follow-up visit AUC was defined as the area under the curve.
Trial Locations
- Locations (138)
Pacific Cancer Medical Center
🇺🇸Anaheim, California, United States
Innovative Clinical Research Institute
🇺🇸Whittier, California, United States
Reading Hospital and Medical Center
🇺🇸Reading, Pennsylvania, United States
Fundacao Pio Xii Hospital de Cancer de Barretos
🇧🇷Barretos, Brazil
Incan - Instituto Do Cancer - Hospital Pompeia
🇧🇷Caxias Do Sul, Brazil
Centro Regional Integrado de Oncologia
🇧🇷Fortaleza, Brazil
Oncosite - Centro de Pesquisa Clinica E Oncologia
🇧🇷Ijui, Brazil
Clinica de Neoplasias Litoral Ltda
🇧🇷Itajai, Brazil
Hospital Do Cancer de Londrina
🇧🇷Londrina, Brazil
Instituto Mederi de Pesquisa E Saude
🇧🇷Passo Fundo, Brazil
Scroll for more (128 remaining)Pacific Cancer Medical Center🇺🇸Anaheim, California, United States