A Randomized, Double Blind, Phase 3 Study of Platinum-Based Chemotherapy With or Without INCMGA00012 in First-Line Metastatic Squamous and Nonsquamous Non–Small Cell Lung Cancer (POD1UM-304)
- Trial ID
- 2022-501987-16-00
- Protocol
- INCMGA 0012-304
- Sponsor
- Incyte Corp.
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to compare the **overall survival (OS)** of patients with metastatic nonsquamous or squamous non-small cell lung cancer receiving a combination of INCMGA00012 and chemotherapy versus those receiving a placebo and chemotherapy. This is clinically relevant as it aims to determine the efficacy of INCMGA00012 in extending the lifespan of patients with this type of cancer, which is crucial for improving treatment outcomes.
Secondary objectives include:
- Comparing the **progression-free survival (PFS)** of the two treatment groups to assess the duration patients remain free from disease progression.
- Comparing the **objective response rate (ORR)** to evaluate the proportion of patients with a significant reduction in tumor size.
- Comparing the **duration of response (DOR)** to determine how long the response to treatment lasts.
- Evaluating the safety and tolerability of the treatment combinations to ensure patient safety and manage adverse effects.
- Assessing the **pharmacokinetics (PK)** of INCMGA00012 when administered with chemotherapy to understand the drug's behavior in the body.
Participants
The clinical trial involves a total of **562 participants** diagnosed with **metastatic nonsquamous or squamous non-small cell lung cancer**. The study population includes both male and female subjects, aged 18 years and older, who have been confirmed to have Stage IV non-small cell lung cancer. Participants were selected based on their ability to comprehend and sign an informed consent form, adequate organ function, and a life expectancy of at least three months. The trial includes individuals who have not received prior systemic treatment for advanced or metastatic non-small cell lung cancer, except for specific neoadjuvant or adjuvant therapies completed at least 12 months prior to the development of metastatic disease. Participants are required to have measurable disease as per RECIST v1.1 criteria and an ECOG performance status of 0 or 1. Both male and female participants must agree to take appropriate precautions to avoid pregnancy or fathering children during and after the trial period. The trial population includes vulnerable individuals, and lifestyle considerations such as diet and physical activity are not specified in the available data.
Plans and Procedures
The clinical trial is designed as a **randomized, double-blind, controlled** study to evaluate the efficacy of a combination therapy involving INCMGA00012 and platinum-based chemotherapy in patients with **metastatic non-small cell lung cancer** (NSCLC). The trial aims to compare overall survival (OS) between the treatment group receiving INCMGA00012 with chemotherapy and the control group receiving a placebo with chemotherapy. The study is expected to run from May 2020 to June 2025, with an estimated participant involvement duration of up to 24 months, depending on individual response and treatment tolerance.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to assess eligibility based on criteria such as age, organ function, and disease status. This visit will include a comprehensive evaluation, including laboratory tests and imaging, to confirm the diagnosis of NSCLC and assess the absence of specific driver mutations. Following randomization, participants will attend regular follow-up visits to monitor treatment response, adverse events, and overall health status. These visits will include assessments of measurable disease per RECIST v1.1 criteria and evaluations of performance status. The end-of-study visit will occur after the completion of the treatment period or upon early termination.
Participants may be withdrawn from the study early if they experience unacceptable adverse events, disease progression, or if they and their investigator decide to switch to an approved and reimbursed standard treatment option that becomes available during the study. The primary endpoint of the trial is overall survival, while secondary endpoints include progression-free survival (PFS), objective response rate (ORR), duration of response (DOR), and the incidence of adverse events (AEs). The trial will also assess pharmacokinetic parameters of the investigational product. The study is conducted under strict adherence to ethical guidelines and regulatory requirements, ensuring the safety and well-being of all participants.
Treatment
The clinical trial involves the administration of several experimental medications, each with specific pharmaceutical forms, dosages, and administration routes. **Pemetrexed Sandoz** is provided as a 500 mg powder for concentrate for solution for infusion. The active substance is **pemetrexed disodium**, and it is administered intravenously. The maximum daily dose is 500 mg/m², with a total dose not exceeding 17,500 mg/m² over a treatment period of up to 24 weeks.
**Carboplatin Bendalis** is a 10 mg/ml concentrate for solution for infusion, containing the active substance **carboplatin**. It is also administered intravenously, with a maximum daily dose of 900 mg and a total dose of 3,600 mg over a 3-week treatment period.
**Albotiva** is a 25 mg/ml concentrate for solution for injection/infusion, containing **pemetrexed diacid monohydrate**. It is administered intravenously, with a maximum daily dose of 500 mg/m² and a total dose of 17,500 mg/m² over a 24-week treatment period.
**Cisplatin NeoCorp** is a 1 mg/ml concentrate for solution for infusion, with **cisplatin** as the active substance. It is administered intravenously, with a maximum daily dose of 75 mg/m² and a total dose of 300 mg/m² over a 3-week treatment period.
**Pemetrexed Accord** is available in two forms: a 100 mg powder for concentrate for solution for infusion and a 25 mg/ml concentrate for solution for infusion. Both forms contain **pemetrexed** and are administered intravenously, with a maximum daily dose of 500 mg/m² and a total dose of 17,500 mg/m² over a 24-week treatment period.
**Cisplatino Accord Healthcare Italia** is a 1 mg/ml concentrate for solution for infusion, containing **cisplatin**. It is administered intravenously, with a maximum daily dose of 75 mg/m² and a total dose of 300 mg/m² over a 3-week treatment period.
**Carboplatin Accord** is a 10 mg/ml concentrate for solution for infusion, containing **carboplatin**. It is administered intravenously, with a maximum daily dose of 900 mg and a total dose of 3,600 mg over a 3-week treatment period.
**Bendatax** is a 6 mg/ml solution for infusion, containing **paclitaxel**. It is administered intravenously, with a maximum daily dose of 200 mg/m² and a total dose of 800 mg/m² over a 4-week treatment period.
**Abraxane** is a 5 mg/ml powder for dispersion for infusion, containing **paclitaxel albumin-bound**. It is administered intravenously, with a maximum daily dose of 100 mg/m² and a total dose of 1,200 mg/m² over a 3-week treatment period.
**Cisplatinum Accord** is a 1 mg/ml concentrate for solution for infusion, containing **cisplatin**. It is administered intravenously, with a maximum daily dose of 75 mg/m² and a total dose of 300 mg/m² over a 3-week treatment period.
**Retifanlimab (INCMGA00012)** is a solution for infusion, containing **retifanlimab**. It is administered intravenously, with a maximum daily dose of 375 mg and a total dose of 13,125 mg over a 24-week treatment period.
**Paclitaxel AqVida** is a 6 mg/ml concentrate for solution for infusion, containing **paclitaxel**. It is administered intravenously, with a maximum daily dose of 200 mg/m² and a total dose of 800 mg/m² over a 3-week treatment period.
The study also includes a **placebo** liquid, which does not contain the active substance but is otherwise identical to INCMGA0012. The placebo is used to maintain the double-blind nature of the trial.
Efficacy
The efficacy of the clinical trial will be assessed using several primary and secondary endpoints. The primary endpoint is overall survival (OS), defined as the time from randomization until death due to any cause. Secondary endpoints include progression-free survival (PFS), overall response rate (ORR), duration of response (DOR), and the number of participants experiencing adverse events (AEs) or discontinuing the study drug due to AEs. PFS is defined as the time from randomization until disease progression by RECIST v1.1 as determined by blinded independent central review (BICR) or death due to any cause. ORR is defined as the proportion of participants who have a confirmed complete response (CR) or partial response (PR) per RECIST v1.1 based on BICR. DOR is 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.
Population pharmacokinetic (PK) parameters, including maximum concentration (Cmax) and area under the curve (AUC), will also be summarized. The efficacy parameters will be measured and collected at various timepoints throughout the trial, with specific methods and schedules for analysis. The trial is designed to compare the efficacy of the combination of INCMGA00012 and chemotherapy versus placebo and chemotherapy in patients with metastatic squamous and nonsquamous non-small cell lung cancer (NSCLC). The trial will utilize validated scales and laboratory tests to ensure accurate and reliable data collection and analysis.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Ability to comprehend and willingness to sign a written ICF for the study.
- Is at least 18 years of age on the day of signing the ICF (or as applicable per local country requirements)
- Has histologically or cytologically confirmed diagnosis of NSCLC (either nonsquamous or squamous) that is Stage IV (AJCC v8). a. Documentation for absence of driver mutations or gene rearrangements for EGFR, ALK, BRAF, and ROS1 if the tumor is of nonsquamous histology. Note: If documentation does not exist for all 4 driver mutations, then archived or fresh tumor tissue material must be tested locally, or centrally arranged by the sponsor. Detailed information is found in the Laboratory Manual. b. If participant's tumor is known to have a predominantly squamous histology, molecular testing for EGFR mutation, ALK, BRAF, and ROS1 translocations will not be required, as this is not part of current diagnostic guidelines. c. Tumor with mixed histology will be categorized by the predominant cell type; if small cell elements are present, the participant is ineligible. In cases where it is not completely known, testing must occur.
- No prior systemic treatment for the advanced/metastatic NSCLC with the exception of neoadjuvant or adjuvant therapy that did not include a PD-(L)1 directed therapy and completed at least 12 months before the development of metastatic disease. Note: Only participants without access (due to inadequate reimbursement, labelling restrictions, or any other reason) to the best standard treatment options (eg, an approved PD-(L)1 inhibitor in combination with chemotherapy or monotherapy) that, according to the investigator, could benefit the participant more can be included in the study. If the best approved and reimbursed standard treatment options become available during the study, the participant may discontinue from study treatment if the investigator and the participant believe that the participant could benefit more by switching to the approved and reimbursed standard treatment.
- Able to provide a formalin-fixed archival tumor tissue sample during screening, or a fresh tumor biopsy after a participant has been diagnosed with metastatic disease, for central confirmation of PD-L1 status. Note: Biopsy should be from a tumor site that has not been treated with radiation. Formalin-fixed archival specimens after the participant has been diagnosed with metastatic disease will be preferred for determination of PD-L1 status (and driver mutations if needed) prior to randomization
- Has measurable disease per RECIST v1.1 as determined by local site investigator/radiology assessment. Target lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
- Has an ECOG performance status of 0 or 1 at study entry
- Has a life expectancy of at least 3 months before signing the ICF
- Willingness to avoid pregnancy or fathering children based on the criteria below: a. Men must agree to take appropriate precautions to avoid fathering children (with at least 99% certainty) from screening through 180 days after the last dose of chemotherapy and 120 days after the last dose of INCMGA00012 and must refrain from donating sperm during this period. Permitted methods that are at least 99% effective in preventing pregnancy (see Appendix A) should be communicated to the participants and their understanding confirmed. b. A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least 1 of the following conditions applies: − Women of childbearing potential must have a negative pregnancy test at screening (within 72 hours of the first dose on Day 1). Women of childbearing potential must agree to take appropriate precautions to avoid pregnancy (with at least 99% certainty) from screening through 180 days after the last dose of chemotherapeutic agents and for at least 120 days after the last dose of INCMGA00012. Permitted methods that are at least 99% effective in preventing pregnancy (see Appendix A) should be communicated to the participants and their understanding confirmed. − Women of nonchildbearing potential (see Appendix A for definitions) are eligible.
- Has adequate organ function as indicated by the laboratory values in Table 7. Specimens must be collected and reviewed within 10 days prior to the start of study treatment.
- Has had an evaluation by the investigator regarding vaccination against SARS-CoV-2 before study entry. Note: Vaccination before study entry is a strong recommendation, not a requirement. Potential participants and the investigator should discuss up-to-date information according to national or local vaccination programs and/or oncology professional guidelines.
Exclusion Criteria
- Is currently participating and receiving investigational therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
- Received prior systemic cytotoxic chemotherapy, targeted or biological therapy for metastatic disease therapy with an anti–PD-1/PDL1/PD-L2, anti-CD137, or anticytotoxic T-lymphocyte–associated antigen-4 antibody, or any other antibody or drug specifically targeting T-cell costimulation or checkpoint pathways.
- Has clinically significant or impaired cardiac disease including acute myocardial infarction, unstable angina, or New York Heart Association Class III or IV CHF within 6 months before study Day 1. Has other clinically significant heart disease (ie, ≥ uncontrolled Grade 3 hypertension) before study Day 1. Medically controlled arrhythmia stable on medication for at least 14 days before study Day 1 is permitted.
- Had any major surgery within 3 weeks of the first dose of study treatment.
- Received thoracic radiation therapy of > 30 Gy within 6 months of the first dose of study treatment.
- Has a history of peripheral neuropathy ≥ Grade 2 CTCAE v5 for participants who may receive cisplatin, paclitaxel, or nab-paclitaxel
- Has untreated CNS metastases and/or carcinomatous meningitis identified either on the baseline brain imaging obtained during the screening period OR identified before signing the ICF
- Evidence of interstitial lung disease or history of interstitial lung disease, or has history of noninfectious pneumonitis that required systemic steroids or has active pneumonitis.
- Has an active infection requiring IV 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
- Has symptomatic ascites or pleural effusion. A participant who is clinically stable following treatment for these conditions is eligible
- Has known active HBV or HCV as defined in protocol
- Has a known history of HIV infection. HIV testing is not required unless mandated by the local health authority, or local regulations
- Has a known history of an additional malignancy, except if the participant has undergone potentially curative therapy with no evidence of that disease recurrence for 3 years since initiation of that therapy
- Has had an allogeneic tissue/solid organ transplant
- Previously had a severe hypersensitivity reaction to treatment with a monoclonal antibody or has a known sensitivity to any component of INCMGA00012 or as applicable, to carboplatin, cisplatin, paclitaxel, nab-paclitaxel, or pemetrexed.
- Is unable to interrupt aspirin or other NSAIDS, other than an aspirin dose ≤ 1.3 g per day, for a 5-day period (8-day period for long acting agents)
- Is unable or unwilling to take folic acid or vitamin B12 supplementation
- Has an active autoimmune disease that has required systemic treatment in past 2 years (ie, with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (eg,thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is allowed
- Is receiving systemic antibiotics or steroid therapy ≤ 7 days prior to the first dose of study treatment or receiving any other form of immunosuppressive medication. a. Corticosteroid use after randomization is allowed for management of AEs, SAEs, as a premedication for IV contrast, or if considered necessary for a participant's welfare. b. Participants who receive daily steroid replacement therapy ≤ 10 mg prednisone or equivalent are exempt. c. Participants with asthma that requires intermittent use of bronchodilators, inhaled steroids, or local steroid injections may participate (are allowed to participate). d. Participants using topical, ocular, intra-articular, or intranasal steroids (with minimal systemic absorption) may participate
- 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). a. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, BCG, and typhoid vaccine
- Current use of any prohibited medication as described in Section 6.6.3
- Has a history or current evidence of any condition including psychiatric or substance abuse disorders, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's ability to participate, or cooperate, for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Bulgaria | Not Recruiting | 05 May 2020 | 7 |
 Czechia | Not Recruiting | 05 May 2020 | 7 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Paclitaxel AqVida 6 mg/ml Konzentrat zur Herstellung einer Infusionslösung | Test | KONZENTRAT ZUR HERSTELLUNG EINER INFUSIONSLÖSUNG | INTRAVENOUS USE | 200 | 3 | PRD5797516 |
Abraxane 5 mg/ml powder for dispersion for infusion. | Test | POWDER FOR DISPERSION FOR INFUSION | INTRAVENOUS USE | 100 | 3 | PRD9254301 |
Pemetrexed Accord 500 mg powder for concentrate for solution for infusion. | Test | POWDER FOR CONCENTRATE FOR SOLUTION FOR INFUSION | INTRAVENOUS USE | 500 | 24 | PRD3636607 |
Cisplatinum Accord, 1 mg/ml, koncentrat do sporządzania roztworu do infuzji. | Test | KONCENTRAT DO SPORZADZANIA ROZTWORU DO INFUZJI | INTRAVENOUS USE | 75 | 3 | PRD1951610 |
Cisplatino Accord Healthcare Italia 1 mg/ml concentrato per soluzione per infusione | Test | CONCENTRATO PER SOLUZIONE PER INFUSIONE | INTRAVENOUS USE | 75 | 3 | PRD3327490 |
Albotiva 25 mg/ml Konzentrat zur Herstellung einer Infusionslösung | Test | KONZENTRAT ZUR HERSTELLUNG EINER INFUSIONSLÖSUNG | INTRAVENOUS USE | 500 | 24 | PRD4193331 |
Bendatax 6 mg/ ml | Test | SOLUTION FOR INFUSION | INTRAVENOUS USE | 200 | 4 | PRD2957674 |
Carboplatin Bendalis 10 mg/ml
Konzentrat zur Herstellung einer Infusionslösung | Test | KONZENTRAT ZUR HERSTELLUNG EINER INFUSIONSLÖSUNG | INTRAVENOUS USE | 900 | 3 | PRD2832939 |
Cisplatin NeoCorp 1 mg/ml - Konzentrat zur Herstellung einer Infusionslösung | Test | KONZENTRAT ZUR HERSTELLUNG EINER INFUSIONSLÖSUNG | INTRAVENOUS USE | 75 | 3 | PRD759858 |
Pemetrexed Accord 25 mg/ml concentrate for solution for infusion | Test | CONCENTRATE FOR SOLUTION FOR INFUSION | INTRAVENOUS USE | 500 | 24 | PRD8505444 |