The FDA cleared a slate of oncology approvals in December 2025, expanding treatment options across hematologic malignancies, solid tumors and transplant-related complications. Decisions ranged from converted approvals for targeted agents to first-in-class cellular and subcutaneous formulations, with several actions hinging on genomically defined populations.
12/3 — Pirtobrutinib (Jaypirca) received full approval for adult patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) previously treated with a covalent BTK inhibitor. The decision was supported by phase 3 BRUIN CLL-321, in which pirtobrutinib improved progression-free survival (median 11.2 vs 8.7 months; HR 0.58; 95% CI, 0.38–0.89; P = .0105) versus investigator’s choice (idelalisib plus rituximab or bendamustine plus rituximab). Overall survival analyses were confounded by high crossover. Regulators cited the PFS benefit, tolerability and low discontinuation rates in a heavily pretreated population.
12/4 — Lisocabtagene maraleucel (liso-cel; Breyanzi) was approved for adults with relapsed or refractory marginal zone lymphoma (MZL) after at least two prior systemic therapies. Data from the MZL cohort of TRANSCEND FL showed an overall response rate of 84.4% (95% CI, 74.4%–91.7%) and a complete response rate of 55.8% (95% CI, 44.1%–67.2%), with median duration of response not reached. The agency noted this expands CAR T-cell therapy into MZL, offering deep and durable remissions where options are limited.
12/9 — Omidubicel-onlv (Omisirge) was cleared for adults and pediatric patients aged 6 years and older with severe aplastic anemia (SAA) undergoing reduced-intensity conditioning who lack a compatible donor. An ongoing phase 1/2 study showed early sustained neutrophil engraftment (median 11 days; range 7–20), and interim ASH data reported rapid neutrophil recovery in 95% of heavily pretreated patients (median 8 days), high disease-free and overall survival rates (~94%) and low rates of graft-versus-host disease. The approval marks the first FDA‑approved hematopoietic stem cell transplant therapy for this population.
12/12 — The agency approved niraparib in combination with abiraterone acetate plus prednisone for adult patients with deleterious or suspected deleterious BRCA2‑mutated metastatic castration‑sensitive prostate cancer (mCSPC), as identified by an FDA‑approved test. An exploratory analysis of the phase 3 AMPLITUDE trial showed a radiographic PFS benefit in BRCA2‑mutated patients (median not estimable vs 26 months; HR 0.46; 95% CI, 0.32–0.66) and delayed time to symptomatic progression (HR 0.41; 95% CI, 0.26–0.65). No rPFS benefit was seen in patients without BRCA2 mutations, underscoring the role of early molecular testing.
12/15 — Fam‑trastuzumab deruxtecan‑nxki (T‑DXd; Enhertu) plus pertuzumab (Perjeta) was approved as frontline therapy for adults with unresectable or metastatic HER2‑positive breast cancer. DESTINY‑Breast09 demonstrated a blinded independent review PFS improvement (median 40.7 vs 26.9 months; HR 0.56; 95% CI, 0.44–0.71; P < .0001). Confirmed objective response rates were 87% with the T‑DXd combination versus 81% with trastuzumab, pertuzumab and a taxane. Overall survival data were immature but showed an early trend favoring the new regimen.
12/17 — Rucaparib (Rubraca) gained regular approval for adults with BRCA mutation–associated metastatic castration‑resistant prostate cancer (mCRPC) after prior androgen receptor‑directed therapy. TRITON3 results showed improved radiographic PFS versus physician’s choice (median 11.2 vs 6.4 months; HR 0.50; 95% CI, 0.36–0.69; P < .0001). Median overall survival was 23.2 months with rucaparib versus 21.2 months for comparators (HR 0.91). Regulators highlighted that benefit was driven primarily by BRCA‑mutated disease, reinforcing targeted testing.
12/18 — A subcutaneous formulation of amivantamab with hyaluronidase‑lpuj (Rybrevant Faspro) was approved for patients with EGFR‑mutated non‑small cell lung cancer across the previously approved indications for intravenous amivantamab. PALOMA‑3 showed noninferior pharmacokinetics versus IV dosing when given with lazertinib and comparable clinical activity (objective response rates ~30% vs 33%). Median PFS was 6.1 months for subcutaneous versus 4.3 months for IV, and median overall survival favored the subcutaneous formulation (HR 0.62; 95% CI, 0.42–0.92). The subcutaneous option is expected to reduce administration time and infusion‑related resource use.
12/22 — Subcutaneous mosunetuzumab (Lunsumio VELO) was cleared for adults with relapsed or refractory follicular lymphoma after two or more prior systemic therapies. The GO29781 study reported a 75% overall response rate (95% CI, 64%–83%), a 59% complete response rate (95% CI, 48%–69%), median duration of response of 22.4 months and median PFS of 23.7 months. Cytokine release syndrome occurred in 29.8% of patients and resolved in all cases. The subcutaneous, fixed‑duration regimen aims to preserve efficacy while lowering treatment burden.
12/30 — Narsoplimab‑wuug (Yartemlea) was approved for adults and pediatric patients aged 2 years and older with hematopoietic stem cell transplant–associated thrombotic microangiopathy (TA‑TMA). A single‑arm study and expanded access data demonstrated a TMA complete response rate of 61% (95% CI, 40.6%–78.5%), improvements in platelet counts and organ function, and an approximate 73% 100‑day survival from TMA diagnosis. This is the first FDA‑approved therapy for HSCT‑associated TA‑TMA.
Other regulatory action included premarket approval of the IsoPSA in vitro diagnostic kit as a blood‑based aid for diagnosing high‑grade prostate cancer in men aged 50 and older with elevated prostate‑specific antigen levels.
Collectively, the December approvals expand targeted and cellular treatment options, introduce more convenient subcutaneous formulations and emphasize the increasing role of genomic testing in guiding therapy selection.
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