Braftovi + Mektovi significantly improves objective response rates in metastatic non-small cell lung cancer

The objective response rate (ORR) was 75% (95% CI: 62, 85) in treatment-naïve patients (n=59), and almost two-thirds (59%) of them maintained a response for at least 12 months. For previously treated patients (n=39), the ORR was 46% (95% CI: 30, 63), with one-third (33%) maintaining a response for at least 12 months. Median progression-free survival (PFS) was not estimable (NE) at data cutoff for the treatment-naïve group (95% CI: 15.7, NE) and 9.3 months (95% CI: 6.2, NE) for the previously treated group. Median overall survival (OS) was NE for either subgroup at the time of data cutoff.

These findings were simultaneously published in the Journal of Clinical Oncology (JCO) and presented during the poster discussion session “Lung Cancer — Non-Small Cell Metastatic” at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago on June 4 (abstract 9018).

The ongoing, single-arm, open-label, multicenter Phase II PHAROS trial (NCT03915951) has enrolled a total of 98 patients with BRAF V600E-mutant metastatic NSCLC, all of whom received Braftovi + Mektovi. The primary endpoint was confirmed ORR, assessed by independent radiology review (IRR). Secondary endpoints include duration of response, disease control rate, PFS and time to response – all assessed by IRR – as well as OS and safety. A majority of adverse events (AEs) observed in the PHAROS trial were Grade 1 or 2 in severity. The most common treatment-related AEs (TRAEs) were nausea (50%), diarrhea (43%), and fatigue (32%). TRAEs led to dose reductions in 24 (24%) patients and permanent treatment discontinuation in 15 (15%) patients. One Grade 5 TRAE of intracranial hemorrhage was reported. The safety profile from PHAROS is consistent with that observed in the approved melanoma indication.

“BRAF V600E-mutant metastatic non-small cell lung cancer tends to be aggressive and resistant to chemotherapy. In the PHAROS trial, we saw that targeted combination therapy with Braftovi + Mektovi provided a clinical benefit to these patients, regardless of prior treatment, while maintaining a manageable safety profile,” said lead investigator Gregory Riely, M.D., Ph.D., Vice Chair, Clinical Research in the Department of Medicine at Memorial Sloan Kettering Cancer Center (MSK). “If approved, Braftovi + Mektovi could become an important new treatment choice for patients with BRAF V600E-mutant metastatic non-small cell lung cancer, where effective new options with manageable safety profiles are needed.”

In April 2023, Pfizer announced that the FDA is reviewing the company’s Supplemental New Drug Applications (sNDAs) for Braftovi + Mektovi for patients with metastatic NSCLC with a BRAF V600E mutation, as detected by an FDA-approved test. These sNDAs are supported by results from the PHAROS trial. The Prescription Drug User Fee Act (PDUFA) goal date for a decision by the FDA is in Fourth-Quarter 2023.

In the U.S., Braftovi + Mektovi is currently approved for the treatment of patients with unresectable or metastatic melanoma with a BRAF V600E or V600K mutation, as detected by an FDA-approved test. Braftovi is also approved, in combination with cetuximab, for the treatment of adult patients with metastatic colorectal cancer (CRC) with a BRAF V600E mutation, as detected by an FDA-approved test, after prior therapy.

See- "Phase II, Open-Label Study of Encorafenib Plus Binimetinib in Patients With BRAFV600-Mutant Metastatic Non–Small-Cell Lung Cancer"-Gregory J. Riely , MD, PhD; Egbert F. Smit , MD, PhD; Myung-Ju Ahn , MD, PhD; et al; ...DOI: 10.1200/JCO.23.00774 Journal of Clinical Oncology. Published online June 04, 2023. PMID: 37270692.