Merck and Gilead report mixed outcomes in lung cancer and HIV studies

Key Takeaways

• KEYNOTE-D46/EVOKE-03 (NCT05609968) was discontinued after eDMC review of final PFS and interim OS in ~620 patients with PD-L1 TPS ≥50% mNSCLC.
• Trodelvy plus KEYTRUDA showed a numerical PFS improvement versus KEYTRUDA alone that did not reach statistical significance; OS benefit was judged unlikely.
• ISLEND-1 and ISLEND-2 met Week 48 primary endpoints for once-weekly islatravir 2 mg/lenacapavir 300 mg, with non-inferiority versus daily comparators.
• Gilead and Merck plan to file the ISLEND Phase 3 package with regulators; detailed HIV numbers were reserved for a future congress.

Why did Merck and Gilead halt the lung cancer combo trial?

The partners discontinued KEYNOTE-D46/EVOKE-03 after an external Data Monitoring Committee reviewed the pre-specified final progression-free survival analysis and an interim overall survival look.

According to the June 8, 2026 Business Wire release, Trodelvy plus KEYTRUDA showed a numerical PFS improvement versus KEYTRUDA monotherapy that did not reach statistical significance, and the probability of meeting the OS endpoint was considered unlikely.

What population and design defined KEYNOTE-D46/EVOKE-03?

The global, open-label, randomized Phase 3 trial, sponsored by Merck, enrolled about 620 patients with previously untreated metastatic NSCLC whose tumors expressed PD-L1 at TPS ≥50% and lacked sensitizing EGFR, ALK, or ROS1 alterations.

Dual primary endpoints were BICR-assessed PFS by RECIST v1.1 and overall survival. More detail is on ClinicalTrials.gov NCT05609968.

• Comparator: KEYTRUDA monotherapy
• Investigational arm: Trodelvy (sacituzumab govitecan-hziy) plus KEYTRUDA
• Safety: combination profile described as consistent with each agent; no new safety signals identified

What did ISLEND-1 and ISLEND-2 show for once-weekly HIV therapy?

On the same news cycle, Gilead and Merck said both Phase 3 ISLEND trials met the primary efficacy endpoint at Week 48 for investigational once-weekly oral islatravir/lenacapavir.

Per the June 8, 2026 Business Wire HIV release, ISLEND-1 tested switch from daily Biktarvy and ISLEND-2 tested switch from standard-of-care daily antiretrovirals; both used the FDA snapshot endpoint of HIV-1 RNA ≥50 copies/mL at Week 48.

• Dose studied: islatravir 2 mg / lenacapavir 300 mg once weekly
• ISLEND-1: statistically non-inferior to Biktarvy
• ISLEND-2: statistically non-inferior to standard-of-care daily ART
• Safety: generally comparable to comparators; no new safety concerns identified

How do these readouts change near-term regulatory and BD watch items?

For oncology, the EVOKE-03 stop removes a first-line PD-L1–high NSCLC path for Trodelvy plus KEYTRUDA that had been framed as a large commercial upside case. Regulatory authorities were informed; investigators were to be notified and patients advised to speak with their physicians.

For HIV, the companies said they plan to file Phase 3 ISLEND data with regulators globally and present detailed findings at a future scientific congress. Exact filing timing was not disclosed in the topline release.

What remains approved today for Trodelvy and KEYTRUDA?

Trodelvy is an FDA-approved Trop-2–directed antibody-drug conjugate for specified metastatic breast and urothelial cancer indications; it is not approved for NSCLC. KEYTRUDA retains multiple FDA-approved NSCLC indications, including first-line use in PD-L1–expressing disease when used per labeled regimens.

Label text and indication language should be checked on FDA Drugs@FDA and the current prescribing information rather than inferred from the discontinued trial.

What remains unproven after these announcements?

The sponsors did not publish detailed PFS hazard ratios, median PFS, or OS curves for EVOKE-03 in the discontinuation release, so magnitude of the numerical PFS difference is not independently verifiable from the press notes alone. For ISLEND, Week 48 virologic failure percentages versus comparators were not quantified in the topline statement. Neither announcement establishes that once-weekly ISL/LEN is approved, nor that Trodelvy plus KEYTRUDA has any NSCLC indication.

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Frequently Asked Questions

Primary Sources

1. Business Wire: KEYNOTE-D46/EVOKE-03 discontinuation (June 8, 2026)
2. Business Wire: ISLEND-1/2 positive topline results (June 8, 2026)
3. ClinicalTrials.gov: NCT05609968 (KEYNOTE-D46/EVOKE-03)
4. FDA Drugs@FDA database