December Roundup of FDA Approvals in Oncology: 9 Decisions to Know

Below is your guide to all the oncologic options that were cleared by the FDA in December 2025. The regulatory roundup provides everything you need to know, right at your fingertips—all the topline findings that supported the decisions and expert insights detailing clinical practice implications.

12/3: Pirtobrutinib in Relapsed/Refractory CLL/SLL

Indication: The FDA granted traditional approval to pirtobrutinib (Jaypirca) for the treatment of adult patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who have previously received a covalent BTK inhibitor.

Supporting data: The regulatory decision was supported by findings from the phase 3 BRUIN CLL-321 trial (NCT04666038), in which the agent significantly improved progression-free survival (PFS) vs investigator’s choice of idelalisib (Zydelig) plus rituximab (Rituxan) or bendamustine (Bendeka) plus rituximab. The median PFS was 11.2 months with pirtobrutinib vs 8.7 months with investigator’s choice (HR, 0.58; 95% CI, 0.38-0.89; P = .0105). Overall survival (OS) analyses were confounded by a high crossover rate, with updated data showing similar OS between arms. Additional analyses revealed improvements in event-free survival and time to next treatment favoring pirtobrutinib.

Clinical significance: This decision converts pirtobrutinib’s prior accelerated approval to full approval and establishes a noncovalent BTK inhibitor option for patients with CLL/SLL who progress on covalent BTK inhibitors. The PFS benefit, along with favorable tolerability and low treatment discontinuation rates, supports the agent as an important therapeutic option in a heavily pretreated population with limited alternatives.

OTHER RELATED COVERAGE

• In a past interview with OncLive®, Paolo Ghia, MD, of Università Vita Salute San Raffaele, highlighted the rationale for evaluating pirtobrutinib for the treatment of patients with relapsed/refractory CLL who had previously received a covalent BTK inhibitor.
• In a recent Insights program, a panel of experts comprised of Catherine C. Coombs, MD, John Allan, MD, and Joanna M. Rhodes, MD, MSCE, explained how the positive phase 3 BRUIN CLL-321 trial results support pirtobrutinib use after covalent BTK inhibitor exposure and consider its role in second-line versus third-line treatment sequencing.
• Data from an analysis of BRUIN CLL-321 shared during the 2025 EHA Congress showed that pirtobrutinib had consistent improvements in patient-reported outcomes (PROs) vs idelalisib plus rituximab or bendamustine plus rituximab in this population.
• In a past Peer Exchange, panelists discussed how real-world experience with pirtobrutinib generally aligns with the BRUIN study’s PFS data while sharing insights about common reasons for discontinuation and interpreting updated BRUIN CLL-321 trial results from the 2024 ASH Annual Meeting that may influence clinical decision-making regarding pirtobrutinib use.

12/4: Liso-Cel for Relapsed/Refractory Marginal Zone Lymphoma

Indication: The regulatory agency cleared lisocabtagene maraleucel (liso-cel; Breyanzi) for use in adult patients with relapsed or refractory marginal zone lymphoma (MZL) who have received at least 2 previous lines of systemic therapy.

Supporting data: The approval was based on results from the MZL cohort of the phase 2 TRANSCEND FL trial (NCT04245839). In the intention-to-treat population, liso-cel induced an overall response rate (ORR) of 84.4% (95% CI, 74.4%-91.7%), which included a complete response (CR) rate of 55.8% (95% CI, 44.1%-67.2%). The median duration of response (DOR) was not reached (NR; 95% CI, 25.59-NR), suggesting durable responses in this heavily pretreated population.

Clinical significance: This approval expands the use of liso-cel beyond follicular lymphoma and establishes the first CAR T-cell therapy option for patients with relapsed or refractory MZL. The high response and CR rates underscore the potential of cellular therapy to deliver deep and durable remissions in a disease setting where treatment options are limited after multiple lines of therapy.

OTHER RELATED COVERAGE

• The primary end point of the MZL cohort of the phase 2 TRANSCEND-FL trial was met in February 2025, when the CAR T-cell therapy induced a statistically significant and clinically meaningful ORR in those with MZL.
• Primary results from the study shared in June 2025 showed that liso-cel led to deep and durable responses in those with relapsed or refractory MZL.

12/9: Omidubicel for Adult and Pediatric Patients With Severe Aplastic Anemia

Indication: The FDA gave the green light to omidubicel-onlv (Omisirge) for use in adult and pediatric patients aged 6 years and older with severe aplastic anemia (SAA) undergoing reduced-intensity conditioning who lack a compatible donor.

Supporting data: The decision was supported by results from an ongoing open-label, single-arm phase 1/2 study (NCT03173937) done in patients with SAA. Among patients in the efficacy population, omidubicel led to early and sustained neutrophil engraftment, with a median time to neutrophil recovery of 11 days (range, 7-20). Interim findings shared at the 2025 ASH Annual Meeting further showed rapid neutrophil recovery in 95% of heavily pretreated patients, with a median time of 8 days, as well as disease-free survival and OS rates of 94% and low rates of graft-vs-host disease (GVHD).

Clinical significance: This decision marks the first FDA-approved hematopoietic stem cell transplant therapy for this population and addresses a critical unmet need in a life-threatening condition. By enabling faster hematopoietic recovery and potentially reducing infectious complications, the drug expands access to curative-intent transplantation and may change the treatment paradigm for SAA.

12/12: Niraparib/Abiraterone Acetate Plus Prednisone for BRCA2+ mCSPC

Indication: The regulatory agency approved niraparib in combination with abiraterone acetate (Akeega) plus prednisone for the treatment of adult patients with deleterious or suspected deleterious BRCA2-mutated metastatic castration-sensitive prostate cancer (mCSPC), as identified by an FDA-approved test.

Supporting data: The decision was supported by data from an exploratory analysis from the phase 3 AMPLITUDE trial (NCT04497844). In patients with BRCA2 mutations, niraparib plus abiraterone and prednisone significantly improved radiographic progression-free survival (rPFS) vs abiraterone and prednisone alone, with a median rPFS that was not estimable vs 26 months, respectively (HR, 0.46; 95% CI, 0.32-0.66). The combination also delayed time to symptomatic progression (HR, 0.41; 95% CI, 0.26-0.65). The rPFS benefit was not observed in patients without BRCA2 mutations.

Clinical significance: This approval introduces the first PARP inhibitor–based combination in the castration-sensitive setting for a genomically defined subgroup of prostate cancer. By demonstrating a clear rPFS benefit restricted to BRCA2-mutated disease, the decision reinforces the importance of early molecular testing in mCSPC and supports precision-based treatment intensification for those most likely to derive meaningful benefit.

OTHER RELATED COVERAGE

• In a recent exclusive interview, Dana E. Rathkopf, MD, of Memorial Sloan Kettering Cancer Center, discussed the AMPLITUDE study in detail—offering insight into the trial design, patient population, efficacy and safety data, and the implications of the research for the field.

• In this OncLive TV clip, Rathkopf discusses the rationale for examining niraparib plus abiraterone acetate in patients with mCSPC: “In the mCRPC setting, the combination of niraparib plus abiraterone [acetate] demonstrated improvement in terms of radiographic progression-free survival, so we decided to [evaluate] this [combination] in [patients with] metastatic castration-sensitive prostate cancer in the phase 3 AMPLITUDE study.”
• In a past Peer Exchange program, panelists Rana R. McKay, MD, Arash Rezazadeh Kalebasty, MD, Sumit K. Subudhi, MD, PhD, Scott T. Tagawa, MD, MS, FACP, and Ulka Vaishampayan, MD, share insight on key ongoing clinical trials in the mCRPC.

12/15: T-DXd Plus Pertuzumab for HER2+ Breast Cancer

Indication: The FDA approved fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) in combination with pertuzumab (Perjeta) for the frontline treatment of adult patients with unresectable or metastatic HER2-positive breast cancer, as determined by an FDA-approved test.

Supporting data: The approval was based on findings from the phase 3 DESTINY-Breast09 trial (NCT04784715). Treatment with T-DXd plus pertuzumab significantly improved PFS vs trastuzumab, pertuzumab, and a taxane (THP), with a median PFS of 40.7 months vs 26.9 months, respectively (HR, 0.56; 95% CI, 0.44-0.71; P < .0001) by blinded independent review. The confirmed ORR was 87% with T-DXd plus pertuzumab vs 81% with standard THP. OS data were immature at the time of analysis but showed an early trend favoring the T-DXd combination.

Clinical significance: This decision establishes an antibody-drug conjugate–based regimen as a new frontline standard for HER2-positive metastatic breast cancer. By delivering a substantial and durable PFS benefit over the long-standing THP regimen, T-DXd plus pertuzumab represents a major shift in first-line management and may redefine treatment sequencing for patients with advanced HER2-positive disease.

OTHER RELATED COVERAGE

• In a recent Rapid Readouts program, Yara Abdou, MD, MSCR, of University of North Caroline, Chapel Hill, Lineberger Comprehensive Cancer Center, details the PROs from the DESTINY-Breast09 trial comparing first-line treatments T-DXd plus pertuzumab vs THP for patients with HER2-positive advanced or metastatic breast cancer.

• The PRO data from DESTINY-Breast09 was identified among the most anticipated data to read out from the 2025 San Antonio Breast Cancer Symposium.
• Prior data from a subgroup analysis of DESTINY-Breast09 was shared during the 2025 ESMO Congress and showed that T-DXd plus pertuzumab generated clinically meaningful PFS outcomes vs THP in patients with HER2-positive advanced or metastatic breast cancer, irrespective of prior treatment, hormone receptor status, or PIK3CA mutation status.
• In a recent Insights program, Komal Jhaveri, MD, FACP, and Kevin Kalinsky, MD, MS, explain how DESTINY-Breast09 data support T-DXd plus pertuzumab in frontline HER2-positive disease for select patients with extensive disease or brain metastases while emphasizing individualized treatment decisions to avoid overtreatment.

12/17: Rucaparib for BRCA Mutation–Associated mCRPC

Indication: The FDA granted regular approval to rucaparib (Rubraca) for use in adult patients with BRCA mutation–associated metastatic castration-resistant prostate cancer (mCRPC) who have received a prior androgen receptor–directed therapy.

Supporting data: The decision was supported by data from the phase 3 TRITON3 trial (NCT02975934), which showed that rucaparib significantly improved rPFS compared with physician’s choice of therapy in patients with BRCA-mutated disease, with a median rPFS of 11.2 months vs 6.4 months, respectively (HR, 0.50; 95% CI, 0.36-0.69; P < .0001). The median OS was 23.2 months with rucaparib and 21.2 months with physician’s choice (HR, 0.91; 95% CI, 0.68-1.20). Exploratory analyses indicated that the clinical benefit was driven primarily by patients harboring BRCA mutations, with minimal benefit observed in those with ATM alterations.

Clinical significance: This regular approval confirms rucaparib as a standard targeted option for patients with BRCA-mutated mCRPC earlier in the disease course, without the requirement for previous chemotherapy. The data reinforce the importance of molecular testing in advanced prostate cancer and clarify that PARP inhibition with rucaparib offers meaningful benefit specifically in BRCA-driven disease rather than across all DNA damage repair alterations.

OTHER RELATED COVERAGE

• Updated data from TRITON3 shared during the 26th Annual Meeting of the Society of Urologic Oncology indicated that rucaparib significantly improved rPFS compared with physician’s choice of docetaxel or androgen receptor pathway inhibition in patients with BRCA-mutated mCRPC, irrespective of age.

• In past Peer Exchange programs, panelists discussed the evolving role of PARP inhibition in the mCRPC setting and ongoing clinical trials that were generating excitement.
• In February 2023, data from TRITON3 were shared during the Genitourinary Cancers Symposium and simultaneously published in the New England Journal of Medicine.
• In October 2022, it was announced that the primary end point of TRITON3 was met when rucaparib monotherapy significantly improved rPFS vs chemotherapy or second-line androgen deprivation therapy in chemotherapy-naive patients with mCRPC harboring BRCA or ATM mutations.

12/18: Subcutaneous Amivantamab for EGFR+ NSCLC

Indication: The FDA cleared amivantamab and hyaluronidase-lpuj (Rybrevant Faspro), a subcutaneous formulation of amivantamab, for use in patients with EGFR-mutated non–small cell lung cancer (NSCLC) across all previously approved indications for intravenous amivantamab (Rybrevant).

Supporting data: The approval was supported by data from the phase 3 PALOMA-3 trial (NCT05388669), which demonstrated noninferior pharmacokinetics for subcutaneous vs intravenous amivantamab when administered with lazertinib. Geometric mean ratios for trough concentrations favored the subcutaneous formulation at cycle 2 day 1 (1.15; 90% CI, 1.04-1.26) and cycle 4 day 1 (1.42; 90% CI, 1.27-1.61), with comparable AUCD1–D15 (1.03; 90% CI, 0.98-1.09). Clinical activity was similar between arms, with ORRs of 30% vs 33% and median PFS of 6.1 vs 4.3 months for subcutaneous and IV formulations, respectively. The median OS favored the subcutaneous formulation at 12.9 months vs not estimable with IV therapy (HR, 0.62; 95% CI, 0.42-0.92).

Clinical significance: This approval expands access to amivantamab by offering a subcutaneous option that maintains efficacy while substantially reducing administration time and infusion-related reactions. The availability of Rybrevant Faspro is expected to improve patient convenience, reduce chair time, and streamline clinic workflows, representing a meaningful advance in the delivery of targeted therapy for patients with EGFR-mutant NSCLC.

OTHER RELATED COVERAGE

• In a past exclusive interview during the 2024 IASLC World Conference on Lung Cancer, Natasha B Leighl, MD, BSc, MMSc, of Princess Margaret Cancer Centre, discusses patient satisfaction and resource utilization results from the phase 3 PALOMA-3 study.

• In a past Rapid Readout, Leighl presented the primary results from PALOMA-3 assessing the OS and noninferiority of subcutaneous amivantamab vs intravenous amivantamab, in combination with lazertinib, in patients with refractory EGFR-mutated, advanced NSCLC.
• Data from PALOMA-3 were shared during the 2024 ASCO Annual Meeting and showed that subcutaneous amivantamab led to a noninferior ORR vs intravenous administration of the agent in patients with refractory advanced NSCLC harboring an EGFR mutation.

12/22: Subcutaneous Mosunetuzumab for Relapsed/Refractory Follicular Lymphoma

Indication: The FDA cleared mosunetuzumab (Lunsumio VELO) as a subcutaneous formulation for the treatment of adult patients with relapsed or refractory follicular lymphoma after 2 or more previous lines of systemic therapy.

Supporting data: The decision was supported by results from the phase 1/2 GO29781 study (NCT02500407). Among patients treated with fixed-duration subcutaneous mosunetuzumab, the ORR was 75% (95% CI, 64%-83%), which included a CR rate of 59% (95% CI, 48%-69%). The median DOR was 22.4 months (95% CI, 16.8-22.8), with additional analyses showing a median PFS of 23.7 months (95% CI, 14.6-NE) and a median OS that was not reached. Efficacy outcomes with the subcutaneous formulation were comparable to those observed with intravenous dosing. Cytokine release syndrome was reported in 29.8% of patients, and all events resolved.

Clinical significance: This approval extends mosunetuzumab into a subcutaneous, fixed-duration option that maintains robust efficacy while reducing administration time and treatment burden. By enabling rapid, outpatient delivery with a manageable safety profile, subcutaneous mosunetuzumab broadens access to bispecific antibody therapy and supports greater use in community practice for patients with relapsed or refractory follicular lymphoma.

OTHER RELATED COVERAGE

• Data previously shared from GO29781 during the 17th International Conference on Malignant Lymphoma showed that fixed-duration treatment with mosunetuzumab monotherapy resulted in a high CR rate by end of treatment in patients with relapsed or refractory follicular lymphoma.
• Findings from an analysis of the study shared during the 2022 ASH Annual Meeting showed that mosunetuzumab elicited durable responses with a low rate of toxicities linked with discontinuation in this population.
• The primary end point of the expansion portion of the trial was met in July 2022 when mosunetuzumab elicited a CR rate that was higher than what has been observed with historical controls in patients with relapsed or refractory follicular lymphoma who had previously received at least 2 prior lines of therapy.
• The trial’s primary end point was met in 2021, with data shared during the ASH Annual Meeting.

12/30: Narsoplimab for Hematopoietic Stem Cell Transplant–Associated Thrombotic Microangiopathy

Indication: The FDA cleared narsoplimab-wuug (Yartemlea) injection for use in adults and pediatric patients aged 2 years and older with hematopoietic stem cell transplant (HSCT)–associated thrombotic microangiopathy (TA-TMA).

Supporting data: The decision was supported by findings from a single-arm, open-label TA-TMA Study in 28 patients, along with data from 19 evaluable patients treated through an expanded access program (EAP). In the TA-TMA Study, treatment with narsoplimab led to a TMA complete response rate of 61% (95% CI, 40.6%-78.5%), with similar response rates observed in the EAP across pediatric and adult patients. Improvements were also seen in platelet counts, lactate dehydrogenase levels, organ function, and transfusion independence, with a 100-day survival rate of approximately 73% from TMA diagnosis across cohorts.

Clinical significance: This decision establishes narsoplimab as the first approved therapy for this life-threatening post-transplant complication, a condition historically managed with supportive care alone. By demonstrating clinically meaningful response rates and survival outcomes in both adult and pediatric populations, narsoplimab represents a practice-changing advance for those who develop TA-TMA following HSCT.

OTHER RELATED COVERAGE

• Data from a phase 2 study previously published in the Journal of Clinical Oncology showed that narsoplimab elicited high response rates and led to a significant improvement in laboratory TMA markers, translating to favorable OS in patients with HSCT-TMA.
• Data shared during the 48th Annual Meeting of the EBMT indicated that a pediatric patient with TA-TMA responded to narsoplimab after experiencing disease progression on eculizumab (Soliris).
• In a past Peer Exchange program, panelists Samer Khaled, MD, Christine N. Duncan, MD, Parameswaran Hari, MD, MRCP, MS, and Jeffrey Lawrence, MD, discussed the results of the phase 2 trial of narsoplimab.
• Another analysis presented during the 47th Annual Meeting of the EBMT showed that pharmacodynamic and pharmacokinetic modeling of narsoplimab supported a weight-based dosing method for patients with HSCT-TMA.

Other Noteworthy Decisions

• The FDA has approved the IsoPSA in vitro diagnostic kit, a novel blood-based prostate cancer test, through the premarket approval process for use as an aid in the diagnosis of high-grade prostate cancer in men at least 50 years of age with elevated prostate-specific antigen levels.

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