Male and female participants at least 18 years of age (or as per adult age applicable per local country requirements) who have metastatic nonsquamous or squamous NSCLC. MedDRA version: 20.1 Level: LLT Classification code 10080083 Term: Advanced lung cancer System Organ Class: 100000004864
Conditions
Sponsors
Incyte Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Ability to comprehend and willingness to sign a written ICF for the study. Note: Vulnerable legal adults who are subject to a measure of legal protection, or are unable to provide expressed consent to participate, according to applicable local health codes and regulations, are excluded. 2. Is at least 18 years of age on the day of signing the ICF (or as applicable per local country requirements). 3. 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. 4. 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. 5. 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. 6. 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. 7. Has an ECOG performance status of 0 or 1 at study entry. 8. Has a life expectancy of at least 3 months before signing the ICF. 9. 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 fo
Exclusion criteria
Exclusion criteria: 1. 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. 2. Received prior systemic cytotoxic chemotherapy, targeted or biological therapy for metastatic disease therapy with an anti–PD-1/PD-L1/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. 3. 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. 4. Had any major surgery within 3 weeks of the first dose of study treatment. 5. Received thoracic radiation therapy of > 30 Gy within 6 months of the first dose of study treatment. 6. Has a history of peripheral neuropathy = Grade 2 CTCAE v5 for participants who may receive cisplatin, paclitaxel, or nab-paclitaxel. 7. 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 8. 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. 9. Has an active infection requiring IV systemic therapy or active tuberculosis. 10. Has symptomatic ascites or pleural effusion. A participant who is clinically stable following treatment for these conditions is eligible. 11. Has known active HBV or HCV defined as follows: a. HBV DNA must be undetectable and HBsAg negative at screening visit. b. Active HCV is defined as a positive HCV antibody result and quantitative HCV-RNA results greater than the lower limits of detection of the assay. 12. Has a known history of HIV infection. HIV testing is not required unless mandated by the local health authority, or local regulations. 13. 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. 14. Has had an allogeneic tissue/solid organ transplant. 15. 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. 16. 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). 17. Is unable or unwilling to take folic acid or vitamin B12 supplementation. 18. 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. 19. Is receiving systemic antibiotics or steroid therapy = 7 days prior to the first dose of study treatment or receiving
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the OS of the combinations of INCMGA00012 and chemotherapy versus placebo and chemotherapy. To compare the PFS of the combinations of INCMGA00012 and chemotherapy versus placebo and chemotherapy.;Secondary Objective: To compare ORR of the combinations of INCMGA00012 and chemotherapy versus placebo and chemotherapy. To compare DOR of the combinations of INCMGA00012 and chemotherapy versus placebo and chemotherapy. To evaluate the safety and tolerability of the combination of INCMGA00012 and chemotherapy and the combination of placebo and chemotherapy. To evaluate the PK of INCMGA00012 375 mg Q3W when administered with chemotherapy ;Primary end point(s): OS, defined as the time from randomization until death due to any cause. PFS, defined as the time from randomization until disease progression by RECIST v1.1 as determined by BICR or death due to any cause.;Timepoint(s) of evaluation of this end point: OS evaluated at each visit PFS evaluated by response every 6 weeks (42 ± 7 days) for 24 weeks, then every 9 weeks (63 ± 7 days) for the next 27 weeks, and subsequently every 12 weeks (84 ± 14 days) until PD is verified by BICR. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): DOR, defined as the time from an initial objective response (CR or PR) according to RECIST v1.1 until first observation of documented disease progression as determined by investigator or death due to any cause. DCR, defined as the proportion of participants with either an objective response PFS, defined as the time from the start of therapy until disease progression, as determined by investigator or death due to any cause. OS, defined as the time from the start of therapy until death due to any cause. Safety, determined by the number of participants, frequency, duration, and severity of AEs, laboratory tests, vital signs, and ECGs. The PK of INCMAG00012 including Cmax, tmax, Cmin, and AUCt, will be summarized.;Timepoint(s) of evaluation of this end point: Throughout the study | — |
Countries
Argentina, Brazil, Bulgaria, China, Czechia, Czech Republic, Hungary, Malaysia, Mexico, Philippines, Poland, Romania, Russian Federation, Serbia, South Africa, Turkey, Ukraine, United States
Contacts
Public ContactClinical Trial Information
Incyte Corporation
Outcome results
None listed