Bristol-Myers Squibb is recruiting 600 participants into a global Phase 3 clinical trial investigating a combination of two immune checkpoint inhibitors — Opdivo (nivolumab) and Yervoy (ipilimumab) — in patients with malignant pleural mesothelioma.
Researchers plan to present the study, “Checkmate 743: A phase 3, randomized, open-label trial of nivolumab (nivo) plus ipilimumab (ipi) vs pemetrexed plus cisplatin or carboplatin as first-line therapy in unresectable pleural mesothelioma,” on June 3 at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago.
Checkmate 743 (NCT02899299) will follow patients with inoperable and previously untreated mesothelioma who have an ECOG performance status score of 0-1. The score — which measures a patient’s ability to handle daily life — indicates that participants will either be physically unrestricted or unable to perform only strenuous activities.
Checkpoint inhibitors are drugs that block molecules which tell the immune system to leave the cancer alone. Two main types of such drugs exist — those that target PD-1 or the factor binding to it — called PD-L1 — and drugs that block CTLA4. The current trial will combine Opdivo, which blocks PD-1, with Yervoy, which acts against CTLA4.
Earlier research suggests that blocking CTLA4 can trigger the appearance of PD-L1 on cancer cells. Although somewhat controversial, researchers use measurements of PD-L1 to test if a PD1-based checkpoint blocker will be effective. High PD-L1 levels often predict good response to treatment.
But in mesothelioma — a cancer that is notoriously difficult to treat — trials with both PD-1 and CTLA4-targeting drugs have only led to minor responses. Despite the fact that researchers reported measurable effects, a Phase 2 trial exploring the investigational CTLA4 drug tremelimumab failed to improve overall survival in mesothelioma patients.
Phase 2 Opdivo data also indicated weak effects in mesothelioma patients who had progressed after treatment with platinum chemotherapy. Five out of 34 had a partial response, and 12 had a stable disease over 12 weeks. Based on the earlier findings, Bristol-Myers Squibb and its partner Ono Pharmaceutical will see if a combination of its Opdivo and Ono’s Yervoy might be better suited in this patient group.
The trial, which will recruit patients at 101 study sites worldwide, will randomize participants to receive either Opdivo and Yervoy, or chemotherapy — Alimta (pemetrexed) plus Platinol (cisplatin) or Paraplatin (carboplatin). Researchers will evaluate overall and progression-free survival — the study’s two primary outcome measures — within a time frame of 3.5 years
The trial will not include patients who have peritoneal, pericardial or tunica vaginalis testis mesothelioma. Also, patients in which the cancer has spread to the central nervous system are ineligible for the study. Enrollment information can be found on the trial page.