What is the Purpose of this Study?
This study focuses on people who have locally advanced, metastatic, or relapsed solid tumor cancer (cancer that can be measured and has worsened and become larger and/or spread to other parts of the body). The study will test 4 study drugs. Participants will be given an investigational drug called mRNA-4359 (an mRNA cancer vaccine) in combination with pembrolizumab, or ipilimumab and nivolumab. The combination of study drugs the participant receives depends on the type of cancer they have. The study will evaluate the safety and effects of mRNA-4359 when given in combination with pembrolizumab or ipilimumab and nivolumab. Researchers also want to determine how well mRNA-4359 works against melanoma and lung cancer when given in combination with pembrolizumab or ipilimumab and nivolumab. Additionally, the study will examine the effects of these drugs on the immune system. When injected into the body, mRNA-4359 tells cells how to make specific proteins, causing some cells to boost specific T cells against specific proteins. It is thought that this could help the immune system have a better chance of finding and killing cancer cells and certain types of immune cells. Pembrolizumab, ipilimumab, and nivolumab are drugs that work by each blocking a specific receptor on the cells. This can help the immune system do a better job of fighting cancer. Giving mRNA-4359 together with the other study drugs may help the immune system to kill more cancer cells. Pembrolizumab, ipilimumab, and nivolumab are approved by the U.S. Food and Drug Administration (FDA) for the treatment of certain types of cancer, but their use in this study is considered investigational.
Eligibility
- * Males or females ≥18 years of age who have provided written informed consent prior to completing any study-specific procedure. For Arm 2d, participants ≥12 years are eligible with informed consent/assent.
- * Dose Escalation (Arm 1a): Participant has histologically confirmed locally advanced or metastatic cancer (cutaneous melanoma, NSCLC, non-muscle invasive bladder cancer, head and neck squamous cell carcinoma, microsatellite stable colorectal cancer \[MSS CRC\], basal cell carcinoma, or triple negative breast cancer) with measurable disease as determined by RECIST v1.1. Arm 1a participants must have received, and then progressed, relapsed, or been intolerant to, or ineligible for, at least 1 standard treatment regimen in the advanced or metastatic setting. Participants with a known driver mutation must have also received or been offered a mutation-directed therapy, where indicated. Participants must have a tumor lesion amenable to biopsy and must have another lesion that can be followed for response.
- * Dose Confirmation (Arm 1b): Participant has histologically confirmed locally advanced or metastatic, and CPI refractory melanoma or locally advanced or metastatic, and CPI refractory NSCLC with measurable disease as determined by RECIST v1.1 who has disease progression after, at least 1 line of standard therapy (no limit to prior lines of therapy), and has been treated with or refused standard of care treatment. Participants in PD arm Group 2 must also have PD-L1 TPS ≥1%. Participants must have primary refractory or acquired secondary resistance to prior immune checkpoint treatments. Primary refractory is defined as prior exposure to anti-programmed death-1 (PD-1)/PD-L1 antibody for at least 6 weeks but no more than 6 months with demonstration of progression on 2 separate scans at least 4 weeks apart but no more than 12 weeks apart and progression occurring within 6 months after first dose of anti-PD-1 antibody. Acquired secondary resistance must have confirmed objective response or prolonged stable disease (SD) (\>6 months), followed by disease progression in the setting of ongoing treatment and confirmed progression on scans at least 4 weeks apart. Participants must have a tumor lesion amenable to biopsy and must have another lesion that can be followed for response.
Where can I participate?
CS Cancer at The Angeles Clinic and Research Institute
More about this Clinical Trial
What is the full name of this clinical trial?
Phase 1/2 Study of mRNA-4359 Administered Alone and in Combination With Immune Checkpoint Blockade in Participants with Advanced Solid Tumors