The goal of this clinical trial is to assess the efficacy of ivonescimab monotherapy in patients with advanced non-small cell lung cancer harboring actionable genomic alterations who have received prior targeted therapies and chemotherapy. This clinical trial also aims to assess the efficacy of ivonescimab plus carboplatin/pemetrexed chemotherapy in patients with advanced non-small cell lung cancer harboring actionable genomic alterations other than epidermal growth factor receptor mutations who have received prior targeted therapies but no chemotherapy. The main questions it aims to answer are:
* Will ivonescimab alone or together with carboplatin/pemetrexed chemotherapy shrink tumors in the clinical trial's patients? * Will ivonescimab alone or together with carboplatin/pemetrexed chemotherapy effectively influence if the patients' cancer grows, how long the treatment takes to start working, how long the treatment keeps working after it first starts to help, how long the treatment keeps the cancer from getting worse, and overall survival of patients? * How many patients receiving ivonescimab alone or together with carboplatin/pemetrexed chemotherapy will experience treatment-emergent, treatment-related, immune-related, and especially interesting side effects? Patients receiving ivonescimab alone will receive an intravenous infusion of ivonescimab every 3 weeks for up to 24 months. Patients receiving ivonescimab together with carboplatin/pemetrexed chemotherapy will receive separate intravenous infusions of ivonescimab, pemetrexed, and carboplatin every 3 weeks for 4 cycles (each cycle is 21 days). These patients will continue to receive infusions of ivonescimab and pemetrexed every 3 weeks for up to 24 total months.
Histologically or cytologically confirmed advanced or metastatic non-squamous NSCLC not amenable to curative resection or radiation.
At least 1 measurable lesion as assessed by investigator per the RECIST v1.1 criteria for both cohorts.
Participants must be willing to undergo the mandatory pre-treatment and post-progression tissue biopsies. If archival pre-treatment tissue is available from within 6 months of study enrollment, with no new intervening systemic therapy since the biopsy, a repeat pre-treatment biopsy may be omitted upon discussion with the principal investigator. On-treatment tissue biopsy (obtained within 7 days prior to Cycle 2 Day 1) will be mandatory for patients in Cohort 1 and optional for patients in Cohort 2. In select cases, if medically deemed unsafe/not feasible, exception may be granted upon discussion with the principal investigator.
Clinically asymptomatic treated or untreated brain metastases are allowed if they have not required increasing doses of steroids within 2 weeks prior to study entry for CNS symptoms.
Participants previously treated with immune checkpoint inhibitors or other T cell immune-modulating antibodies, including anti-CTLA-4, anti-PD-1 and/or anti-PD-L1 agents.
Major surgical procedures or serious trauma within 4 weeks prior to first ivonescimab dose or plans for major surgical procedures within 4 weeks after the first ivonescimab dose (as determined by the investigator). Minor local procedures (excluding central venous catheterization and port implantation) within 3 days prior to first ivonescimab dose.
Hemoptysis (defined as coughing up ≥ 0.5 teaspoon of fresh blood or small blood clots). Note: transient hemoptysis associated with diagnostic bronchoscopy is allowed.
Nasal bleeding/epistaxis (bloody nasal discharge is allowed)
Parallel
Ivonescimab
DrugIvonescimab is a specially engineered antibody that can attach to both PD-1 and VEGF-A.
carboplatin
DrugCarboplatin is a type of chemotherapy drug that contains a special form of platinum.
pemetrexed
DrugPemetrexed is a type of chemotherapy drug that works by blocking specific substances, called folates, that cancer cells need to grow and multiply.
Objective Response Rate (ORR) of Ivonescimab Monotherapy
The objective response rate (ORR) is defined as the number of patients with confirmed best overall response or complete response or partial response (PR) divided by the number of treated patients in the cohort. ORR will be measured per investigator. BOR will be assessed per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) criteria.
Objective Response Rate (ORR) of Ivonescimab plus Carboplatin/Pemetrexed
The objective response rate (ORR) is defined as the number of patients with confirmed best overall response or complete response or partial response (PR) divided by the number of treated patients in the cohort. ORR will be measured per investigator. BOR will be assessed per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) criteria.
Disease Control Rate (DCR) of Ivonescimab Monotherapy
Disease control rate (DCR) is defined as the percentage of participants who have either a complete response, partial response, or stable disease. DCR will be assessed per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) criteria.
Disease Control Rate (DCR) of Ivonescimab plus Carboplatin/Pemetrexed
Disease control rate (DCR) is defined as the percentage of participants who have either a complete response, partial response, or stable disease. DCR will be assessed per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) criteria.
Time to Response (TTR) of Ivonescimab Monotherapy
Time to response (TTR) is defined as the amount of time between the first dose of ivonescimab to the first time that measurement criteria are met for complete response or partial response. TTR will be assessed per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) criteria.
Time to Response (TRR) of Ivonescimab plus Carboplatin/Pemetrexed
Time to response (TTR) is defined as the amount of time between the first doses of ivonescimab, carboplatin, and pemtrexed to the first time that measurement criteria are met for complete response or partial response. TTR will be assessed per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) criteria.
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Massachusetts General Hospital
Lead sponsor
Summit Therapeutics
Collaborator
