Gilead Sciences Inc. and Merck & Co. Inc. discontinued the Phase 3 KEYNOTE-D46/EVOKE-03 trial evaluating the combination of Trodelvy and Keytruda for previously untreated metastatic non-small cell lung cancer with high PD-L1 expression. The decision followed a review by a Data Monitoring Committee of progression-free survival and interim overall survival data. While the combination showed a numerical improvement in progression-free survival, it did not reach statistical significance, and investigators determined the probability of achieving a meaningful overall survival benefit at final analysis was low. The safety profile remained consistent with known profiles, with no new signals identified.

Separately, the companies announced positive Phase 3 results for an investigational once-weekly oral HIV regimen combining islatravir and lenacapavir. The regimen met its primary efficacy endpoint in two studies, ISLEND-1 and ISLEND-2, which evaluated its safety and efficacy in people living with HIV who were already virologically suppressed.

HIV Trial Results

The primary endpoint in both studies measured the percentage of participants with HIV-1 RNA levels of at least 50 copies/mL at Week 48 under the FDA snapshot algorithm. In the ISLEND-1 study, patients switched from Biktarvy to the once-weekly islatravir/lenacapavir regimen. The treatment was found to be statistically non-inferior to Biktarvy. Meanwhile, in the open-label ISLEND-2 trial, the regimen demonstrated statistical non-inferiority compared with standard-of-care daily oral antiretroviral therapies.

The safety profile of the combination was generally comparable to the comparator regimens in both studies, with no new safety concerns identified.

Next Steps for HIV Treatment

Gilead and Merck plan to submit the Phase 3 findings to regulatory authorities worldwide and present detailed data at a future scientific congress. The investigational combination targets multiple stages of HIV-1 replication. If approved, the treatment could offer virologically suppressed patients a long-acting, once-weekly oral single-tablet option.

Gilead Sciences, Inc. and Merck, known as MSD outside of the United States and Canada, announced that the primary efficacy endpoint at Week 48 was met in both the Phase 3 ISLEND-1 and ISLEND-2 trials for the investigational oral once-weekly single-tablet regimen of islatravir 2 mg and lenacapavir 300 mg. The trials evaluated the regimen in people with HIV who are virologically suppressed and switched from BIKTARVY or standard of care antiretroviral regimens. The regimen demonstrated statistical non-inferiority compared to BIKTARVY in the double-blind ISLEND-1 trial and to standard of care daily oral antiretroviral therapy in the open-label ISLEND-2 trial. The safety profile of islatravir/lenacapavir was generally comparable to the comparator regimens studied in the ISLEND trials, with no new safety concerns identified. Gilead and Merck plan to file the Phase 3 data with regulatory authorities globally and submit the detailed findings for presentation at a future scientific congress.

Trial Details and Endpoints

The primary efficacy endpoint for both ISLEND-1 and ISLEND-2 was the percentage of participants with HIV-1 RNA levels ≥ 50 copies/mL at Week 48, defined by the FDA snapshot algorithm. Key secondary endpoints included virologic suppression rates at Week 48 and Week 96, changes in CD4 cell count, and discontinuation due to treatment-emergent adverse events.

Mechanism of Action

Islatravir is Merck's next-generation nucleoside analog that blocks HIV-1 replication by inhibiting reverse transcriptase translocation. Lenacapavir is Gilead's first-in-class capsid inhibitor designed to inhibit HIV at multiple stages of its lifecycle. The combination targets multiple stages of HIV-1 replication, enabling long-acting dosing as a once-weekly tablet.

Jared Baeten, Senior Vice President of Clinical Development at Gilead Sciences, stated that long-acting oral therapies represent a transformational innovation with the potential to reshape HIV care. Dr. Eliav Barr, Senior Vice President and Chief Medical Officer at Merck Research Laboratories, emphasized the commitment to advancing a novel once-weekly oral option to expand treatment choices for people living with HIV.