FDA Approves First-Line Acalabrutinib Regimen for CLL/SLL, Expands NSCLC Dosing Options

The FDA approved acalabrutinib (Calquence) in combination with venetoclax (Venclexta) for the treatment of adult patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), marking the first all-oral, fixed-duration BTK inhibitor–based regimen in this setting. The decision was based on findings from the phase 3 AMPLIFY trial (NCT03836261), which revealed superior progression-free survival (PFS) with the doublet (n = 291) compared with standard chemoimmunotherapy (n = 290), with a 3-year PFS rate of 76.5% (95% CI, 71.0%-81.1%) vs 66.5% (95% CI, 59.8%-72.3%; HR, 0.65; 95% CI, 0.49-0.87; P = .004). The median PFS was not reached with acalabrutinib plus venetoclax vs 47.6 months with the control regimen. Safety data were consistent with known toxicity profiles, with no new signals reported.

The FDA approved a simplified monthly dosing schedule of amivantamab and hyaluronidase-lpuj (Rybrevant Faspro) for frontline use in patients with EGFR-mutated advanced non–small cell lung cancer (NSCLC). This decision was supported by data from the phase 2 PALOMA-2 (NCT05498428) and phase 3 PALOMA-3 (NCT05388669) trials, which demonstrated comparable efficacy to prior dosing schedules when combined with lazertinib (Lazcluze). In PALOMA-2, monthly dosing led to an investigator-assessed objective response rate (ORR) of 82% and reduced administration-related reactions compared with intravenous dosing. No new safety signals were reported, and pharmacokinetic equivalence to earlier regimens was confirmed.

The FDA accepted a new drug application (NDA) seeking approval of tirabrutinib (Velexbru) for the treatment of patients with relapsed or refractory primary central nervous system lymphoma (PCNSL) and set a Prescription Drug User Fee Action (PDUFA) date of December 18, 2026. The application is supported by phase 2 PROSPECT trial (NCT04947319) data, in which single-agent tirabrutinib elicited an ORR of 67% (95% CI, 52%-80%), which included a complete response rate of 44% (95% CI, 29%-59%). The median duration of response (DOR) was 9.3 months (95% CI, 4.6-14.6), and the median time to response was 1 month (range, 0.9-3.7 months). Moreover, the median PFS was 6 months (95% CI, 5.3-11.1), and median overall survival was not yet reached (95% CI, 12.5-not estimable). The safety profile of the agent was manageable, with mostly low-grade cardiac effects and no unexpected toxicities.

The FDA accepted for review an NDA for giredestrant (GDC-9545) in combination with everolimus (Afinitor) for the treatment of patients with ESR1-mutated, estrogen receptor (ER)–positive, HER2-negative advanced breast cancer. In the phase 3 evERA Breast Cancer trial (NCT05306340), the doublet (n = 103) reduced the risk of progression or death by 62% compared with standard endocrine therapy plus everolimus (n = 105) and improved median PFS to 9.99 months (95% CI, 8.08-12.94; HR, 0.38; 95% CI, 0.27-0.54; P < .0001). ORRs and DOR favored the giredestrant arm in the ESR1-mutated population. The safety profile of the combination was reported to be manageable and consistent with known toxicities, with no unexpected adverse effects.

The U.S. Food and Drug Administration approved tumor-treating fields (Optune) combined with chemotherapy for pancreatic cancer — a notable expansion of device-based oncology treatment. Another FDA approval broadened the use of pembrolizumab in oncology, reinforcing the sustained dominance of immunotherapy across tumor types and lines of therapy.

The PATINA trial demonstrated meaningful improvements in progression-free survival with palbociclib in advanced hormone receptor–positive breast cancer. Emerging data suggests that lower-dose immunotherapy may preserve efficacy while reducing toxicity and cost.

Harvey Risch, Professor Emeritus and Senior Research Scientist in Epidemiology at the Yale School of Public Health and Yale School of Medicine, was appointed as Chair of the President's Cancer Panel.