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)
Trakya Universitesi Tip Fakultesi
🇹🇷Edirne, Turkey
Wits Clinical Research
🇿🇦Johannesburg, South Africa
Kherson Regional Oncologic Dispensary
🇺🇦Kherson, Ukraine
University of Pretoria Oncology Department
🇿🇦Pretoria, South Africa
Cne Ccch of Uzh Cc Oncological Center
🇺🇦Uzhgorod, Ukraine
Yildirim Beyazit University Ankara Ataturk Training and Research Hospital
🇹🇷Ankara, Turkey
Necmettin Erbakan Universitesi Meram Tip Fakultesi Hastanesi
🇹🇷Konya, Turkey
Mary Potter Oncology Centre
🇿🇦Pretoria, South Africa
Acibadem Adana Hospital
🇹🇷Adana, Turkey
Clinical Center of Serbia
🇷🇸Belgrade, Serbia
Communal Non-Profit Enterprise Regional Center of Oncology
🇺🇦Kharkiv, Ukraine
Hacettepe Universitesi Tip Fakultesi Hastanesi
🇹🇷Ankara, Turkey
Medical Center Asklepion Llc
🇺🇦Kyiv, Ukraine
Rmi Sumy Regional Clinical Oncology Dispensary
🇺🇦Sumy, Ukraine
Dr. Abdurrahman Yurtaslan Onkology Teaching and Research Hospital
🇹🇷Ankara, Turkey
N.N. Petrov Research Institute of Oncology
🇷🇺St Petersburg, Russian Federation
Clinical Center Bezanijska Kosa
🇷🇸Belgrade, Serbia
Sbhi Volgograd Regional Onclogy Dispensary
🇷🇺Volgograd, Russian Federation
Adana Sehir Hastanesi
🇹🇷Adana, Turkey
Memorial Ankara Hospital
🇹🇷Ankara, Turkey
Cape Town Oncology Trials (Pty) Ltd
🇿🇦Cape Town, South Africa
Ci Carpathian Clinical Oncological Center
🇺🇦Ivano-frankivsk, Ukraine
St. Lukes Medical Center
🇵🇭Quezon City, Philippines
V.T.Zaycev Institute of General and Urgent Surgery of National Academy Medical Sciences of Ukraine
🇺🇦Kharkiv, Ukraine
Sandton Oncology Centre
🇿🇦Johannesburg, South Africa
Gaziantep University Gaziantep Oncology Hospital
🇹🇷Gaziantep, Turkey
Medipol University Medical Faculty
🇹🇷Istanbul, Turkey
Cancercare Rondebosch Oncology Centre
🇿🇦Cape Town, South Africa
Medical Center Oncolife Llc
🇺🇦Zaporizhzhia, Ukraine
National Cancer Hospital
🇻🇳Hanoi, Vietnam
Multifield Clinical Hospital No 4
🇺🇦Dnipro, Ukraine
Can Tho Oncology Hospital
🇻🇳Can Tho, Vietnam
Hcmc Oncology Hospital
🇻🇳Ho Chi Minh City, Vietnam
Pp Ppc Acinus Medical and Diagnostic Centre
🇺🇦Kropyvnytskyi, Ukraine
Kyiv City Clinical Oncological Center
🇺🇦Kyiv, Ukraine
Ci of Krc Kyiv Regional Oncologic Dispensary
🇺🇦Kyiv, Ukraine
Bach Mai Hospital
🇻🇳Hanoi, Vietnam
National Lung Hospital
🇻🇳Hanoi, Vietnam
Volyn Regional Oncological Dispensary
🇺🇦Lutsk, Ukraine
Hunan Cancer Hospital
🇨🇳Changsha, China
The First Affiliated Hospital Sun Yat-Sen University
🇨🇳Guangzhou, China
Sir Run Run Shaw Hospital Zhejiang University School of Medicine
🇨🇳Hangzhou, China
Hangzhou Cancer Hospital
🇨🇳Hangzhou, China
The First Affiliated Hospital of Zhejiang University
🇨🇳Hangzhou, China
Zhejiang Cancer Hospital
🇨🇳Hangzhou, China
University of Science and Technology of China-First Affiliated Hospital (Anhui Provincial Hospital)
🇨🇳Hefei, China
Jinan Central Hospital
🇨🇳Jinan, China
Henan Cancer Hostipal
🇨🇳Zhengzhou, China
Henan Provincial Peoples Hospital
🇨🇳Zhengzhou, China
Memorial Antalya Hastanesi
🇹🇷Antalya, Turkey
Istanbul University Cerrahpasa - Cerrahpasa Medical Faculty
🇹🇷Istanbul, Turkey
Bakirkoy Dr Sadi Konuk Teaching and Research Hospital
🇹🇷Istanbul, Turkey
Inonu Universitesi Turgut Ozal Tip Merkezi
🇹🇷Malatya, Turkey
Fundacao Faculdade Regional de Medicina de Sao Jose Do Rio Preto
🇧🇷Sao Jose, Brazil
The Medical City
🇵🇭Pasig City, Philippines
Spitalul Clinic Judetean de Urgenta Constanta
🇷🇴Constanta, Romania
Oncomed-System
🇷🇸Belgrad, Serbia
Clinical Center Kragujevac
🇷🇸Kragujevac, Serbia
Pacific Cancer Medical Center
🇺🇸Anaheim, California, United States
Innovative Clinical Research Institute
🇺🇸Whittier, California, United States
Centro Regional Integrado de Oncologia
🇧🇷Fortaleza, Brazil
Incan - Instituto Do Cancer - Hospital Pompeia
🇧🇷Caxias Do Sul, Brazil
Oncosite - Centro de Pesquisa Clinica E Oncologia
🇧🇷Ijui, Brazil
Fundacao Pio Xii Hospital de Cancer de Barretos
🇧🇷Barretos, Brazil
Inca - Instituto Nacional de Cancer
🇧🇷Rio de Janeiro, Brazil
Instituto Mederi de Pesquisa E Saude
🇧🇷Passo Fundo, Brazil
Cepho - Centro de Estudos E Pesquisas de Hematologia E Oncologia
🇧🇷Santo Andre, Brazil
Hospital Do Cancer de Londrina
🇧🇷Londrina, Brazil
Sao Camilo Oncologia
🇧🇷S?O Paulo, Brazil
Hgb - Hospital Giovanni Battista - Mae de Deus Center
🇧🇷Porto Alegre, Brazil
Mc Women'S Health-Nadezhda Eood
🇧🇬Sofia, Bulgaria
Acibadem Cityclinica Mhat Tokuda
🇧🇬Sofia, Bulgaria
Umhat Sv. Ivan Rilski Ead
🇧🇬Sofia, Bulgaria
Multiprofile Hospital For Active Treatment Central Onco Hospital Ood
🇧🇬Sofia, Bulgaria
Mhat Serdika Eood
🇧🇬Sofia, Bulgaria
Shatod Dr Marko Marko - Varna Ltd
🇧🇬Varna, Bulgaria
Harbin Medical University Cancer Hospital
🇨🇳Harbin, China
The Second Hospital of Anhui Medical University
🇨🇳Hefei, China
The Second Affiliated Hospital of Nanchang University
🇨🇳Nanchang, China
Linyi Cancer Hospital
🇨🇳Linyi, China
The First Affiliated Hospital of Guangxi Medical University
🇨🇳Nanning, China
Shanghai Chest Hospital
🇨🇳Shanghai, China
General Hospital of Tianjin
🇨🇳Tianjing, China
The Affiliated Cancer Hospital of Xinjiang Medical University
🇨🇳Urumqi, China
University Hospital Hradec Kralove
🇨🇿Hradec Kralove, Czechia
The First Affiliated Hospital of Zhengzhou University
🇨🇳Zhengzhou, China
Fakultni Nemocnice V Motole
🇨🇿Praha 5, Czechia
Fakultni Nemocnice Olomouc
🇨🇿Olomouc, Czechia
Nemocnice Agel Ostrava - Vitkovice A.S
🇨🇿Ostrava - Vitkovice, Czechia
High Technology Hospital Medcenter
🇬🇪Batumi, Georgia
Israel-Georgian Medical Research Clinic Helsicore
🇬🇪Tbilisi, Georgia
Jsc Evex Hospitals
🇬🇪Kutaisi, Georgia
Archangel St. Michael Multi Profile Clinical Hospital
🇬🇪Tbilisi, Georgia
New Hospitals
🇬🇪Tbilisi, Georgia
Tbilisi State Medical University First University Clinic
🇬🇪Tbilisi, Georgia
Medulla Chemotherapy and Immunotherapy Clinic
🇬🇪Tbilisi, Georgia
High Technology Medical Center, University Clinic
🇬🇪Tbilisi, Georgia
Cancer Research Center Ltd
🇬🇪Tbilisi, Georgia
Advanced Medical and Dental Institute Husm
🇲🇾Kepala Batas, Malaysia
Bacs Kiskun Megyei Oktatokorhaz
🇭🇺Kecskemet, Hungary
Orszagos Koranyi Tbc Es Pulmonological Intezet
🇭🇺Budapest, Hungary
University Malaya Medical Centre
🇲🇾Kuala Lumpur, Malaysia
Sarawak General Hospital
🇲🇾Kuching, Malaysia
Hospital Tengku Ampuan Afzan
🇲🇾Kuantan, Malaysia
Hospital Pulau Pinang
🇲🇾Pulau Pinang, Malaysia
Institut Kanser Negara - National Cancer Institute
🇲🇾Putrajaya, Malaysia
Cebu Doctors University Hospital
🇵🇭Cebu City, Philippines
West Visayas State University Medical Center
🇵🇭Iloilo City, Philippines
Davao Doctors Hospital
🇵🇭Davao City, Philippines
Makati Medical Center
🇵🇭Makati, Philippines
Ko-Med Centra Kliniczne Biala Podlaska
🇵🇱Biala Podlaska, Poland
Przychodnia Lekarska Komed
🇵🇱Konin, Poland
Asian Hospital and Medical Center
🇵🇭Muntinlupa, Philippines
Centrum Medyczne Plejady
🇵🇱Krakow, Poland
Centrum Terapii Wspolczesnej J.M. Jasnorzewska Sp. Komandytowo-Akcyjna
🇵🇱Lodz, Poland
Institutul Oncologic Prof. Dr. Ion Chiricuta Cluj-Napoca
🇷🇴Cluj Napoca, Romania
S.C Oncopremium Team S.R.L
🇷🇴Baia Mare, Romania
Przychodnia Med-Polonia Sp. Z O.O.
🇵🇱Poznan, Poland
S C Oncocenter Oncologie Medicala S R L
🇷🇴Timisoara, Romania
Sbih of Arkhangelsk Region Arkhangelsk Clinical Oncological Dispensary
🇷🇺Arkhangelsk, Russian Federation
Rbih Kursk Regional Clinical Oncology Dispensary of Kursk Region Healthcare Committee
🇷🇺Kursk, Russian Federation
Federal State Institution "Russian Cancer Research Center Named After N.N. Blokhin" Rams
🇷🇺Moscow, Russian Federation
Llc Tonus
🇷🇺Nizniy Novgorod, Russian Federation
Sbhi of Novosibirsk Region Novosibirsk Regional Oncological Dispensary
🇷🇺Novosibirsk, Russian Federation
Bhi of Omsk Region Clinical Oncology Dispensary
🇷🇺Omsk, Russian Federation
Pavlov First Saint Petersburg State Medical University
🇷🇺Saint-petersburg, Russian Federation
Izmir Medicalpark Hospital
🇹🇷Izmir, Turkey
Mi Kryviy Rih Center of Dnipropetrovsk Regional Council
🇺🇦Kryvyi Rih, Ukraine
Reading Hospital and Medical Center
🇺🇸Reading, Pennsylvania, United States
Clinica de Neoplasias Litoral Ltda
🇧🇷Itajai, Brazil
Beacon Hospital Sdn Bhd
🇲🇾Petaling Jaya, Malaysia
Spitalul Clinic Militar de Urgenta Dr. Constantin Papilian Cluj-Napoca
🇷🇴Cluj-napoca, Romania
Philippine General Hospital
🇵🇭Manila, Philippines
Institute For Pulmonary Diseases of Vojvodina
🇷🇸Sremska Kamenica, Serbia
103 Military Hospital
🇻🇳Hanoi, Vietnam
Hanoi Oncology Hospital
🇻🇳Hanoi, Vietnam
Institute of Clinical Oncology Ltd
🇬🇪Tbilisi, Georgia
Oncomed Srl
🇷🇴Timisoara, Romania