Introduction
Cancer immunotherapy has revolutionized treatment by leveraging the immune system to combat tumor cells. Immune checkpoint blockades (ICBs), particularly those targeting the PD-1/PD-L1 pathway, have shown significant clinical success. Dostarlimab, a PD-1 inhibitor, has demonstrated clinical activity across various tumor types. This phase 1b trial, IOLite, aimed to explore the safety and efficacy of dostarlimab in combination with other cancer therapies.
Methods
The IOLite trial was a multicenter, open-label study designed to determine the recommended phase 2 dose (RP2D), safety, pharmacokinetics (PK), and preliminary efficacy of dostarlimab combinations. Patients with advanced or metastatic cancer were enrolled into different parts of the study, receiving dostarlimab with niraparib, carboplatin–paclitaxel, or bevacizumab. The study followed a 6+6 dose escalation format to assess tolerability and establish RP2Ds.
Results
- Safety: The combinations were well-tolerated, with the most common grade ≥3 treatment-emergent adverse events being anemia, thrombocytopenia, and neutropenia. Dose-limiting toxicities were observed but did not prevent the establishment of RP2Ds for all combinations.
- Efficacy: Tumor response rates varied across the study parts, with the highest disease control rates observed in combinations including bevacizumab. The dostarlimab plus carboplatin–paclitaxel combination showed an objective response rate (ORR) of 42.9%, and the addition of bevacizumab increased the disease control rate (DCR) to 84.6%.
- Pharmacokinetics: The PK profiles of dostarlimab and niraparib were consistent with monotherapy data, indicating no significant impact from combination therapy.
Discussion
The IOLite trial provides promising evidence for the safety and efficacy of dostarlimab in combination with niraparib or carboplatin–paclitaxel, with or without bevacizumab, in treating advanced solid tumors. The study's findings support further investigation in larger, randomized phase 3 trials to validate these combinations' therapeutic potential across different cancers. The addition of bevacizumab appears to enhance the antitumor activity, suggesting a synergistic effect that warrants further exploration.
