The OncFive: Top Oncology Articles for the Week of 2/15

Welcome to OncLive®’s OncFive!

Every week, we bring you a quick roundup of the 5 top stories from the world of oncology—ranging from pivotal regulatory decisions to key pipeline updates to expert insights on breakthroughs that are moving the needle in cancer care. This resource is designed to keep you informed on the latest updates in the space, in just a matter of minutes.

Here’s what you may have missed this week:

FDA Approves First-Line Acalabrutinib Plus Venetoclax for CLL/SLL

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.

FDA Clears Monthly First-Line Amivantamab and Hyaluronidase Dosing for EGFR-Mutated, Advanced NSCLC

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. “A monthly dosing schedule offers patients convenience without sacrificing efficacy,” Danny Nguyen, MD, of City of Hope, in Duarte, California, stated in a news release.

FDA Accepts NDA for Tirabrutinib in Relapsed/Refractory PCNSL

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.

Giredestrant Plus Everolimus NDA Is Under FDA Review for ESR1-Mutated, ER+ Advanced Breast Cancer

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 clinically meaningful benefit seen with giredestrant could enable an important new treatment option to help delay disease progression or death in people with advanced ER-positive breast cancer,” Levi Garraway, MD, PhD, of Roche, stated in a news release.

FDA Approval Sought for Iberdomide Plus Daratumumab/Dexamethasone in R/R Multiple Myeloma

The FDA accepted an NDA seeking the approval of iberdomide (CC-220) paired with daratumumab (Darzalex) and dexamethasone (IberDd) for use in patients with relapsed or refractory multiple myeloma. A decision date of August 17, 2026, was set under the PDUFA. The filing is based on findings from the phase 3 EXCALIBER-RRMM trial (NCT04975997), which showcased significantly higher minimal residual disease negativity rates with IberDd vs daratumumab, bortezomib (Velcade), and dexamethasone. The trial continues to evaluate PFS and OS as dual primary end points. Iberdomide also received a breakthrough therapy designation from the regulatory agency, highlighting its potential as an oral CELMoD partner to anti-CD38 therapy.

Honorable Mentions

• Selpercatinib (Retevmo) led to a statistically significant and clinically meaningful improvement in investigator-assessed event-free survival compared with placebo as adjuvant therapy in the treatment of patients with early-stage RET fusion–positive NSCLC, meeting the primary end point of the phase 3 LIBRETTO-432 trial (NCT04819100).
• Topline data from cohort 3 of the pivotal phase 3 BREAKWATER trial (NCT04607421) revealed that encorafenib (Braftovi) plus cetuximab (Erbitux) and FOLFIRI (fluorouracil, leucovorin, and irinotecan) significantly improved PFS compared with standard FOLFIRI plus or minus bevacizumab (Avastin) in patients with previously untreated metastatic colorectal cancer harboring a BRAF V600E mutation.