OncLive’s August Roundup of Key FDA Approvals in Oncology: 3 Decisions to Know

Below is your guide to all the oncologic therapeutic options that were cleared by the FDA in August 2025. The roundup provides everything you need to know, right at your fingertips—all the topline data that supported the decisions and expert insights contextualizing what they mean for clinical practice.

8/6: Dordaviprone in Diffuse Midline Glioma

Indication: The FDA has granted accelerated approval to dordaviprone (Modeyso; formerly ONC201) for use in adult and pediatric patients at least 1 year of age with H3K27M-mutant diffuse midline glioma who have progressive disease after previous therapy. This marks the first systemic therapy approved for this biomarker-defined subset of diffuse midline glioma.

Supporting Data: The regulatory decision was based on pooled findings from 5 open-label, nonrandomized US trials: ONC006 (NCT02525692), ONC013 (NCT03295396), ONC014 (NCT03416530), ONC018 (NCT03134131), and ONC016 (NCT05392374). Among 50 patients treated with monotherapy, the objective response rate (ORR) was 22% (95% CI, 12%-36%), with a median duration of response (DOR) of 10.3 months (95% CI, 7.3-15.2). Notably, 73% of responders maintained a response for at least 6 months, and 27% maintained a response for at least 12 months. Additional analyses showed 46.7% of evaluable patients achieved corticosteroid dose reduction of 50% or higher, and 20.6% had improved performance scores.

Clinical Significance: Dordaviprone represents a first-in-class protease activator that establishes a long-awaited treatment option for patients with H3K27M-mutant diffuse midline glioma, a population with limited therapeutic options and poor prognosis. The decision underscores the value of biomarker testing for H3K27M mutations and opens the door for further drug development in primary brain tumors.

In a recent interview with OncLive®, Timothy F. Cloughesy, MD, of UCLA Health Jonsson Comprehensive Cancer Center, discussed the significance of the approval: “[Diffuse midline glioma] is a particularly difficult tumor to manage. Having a therapy available is just a huge win for our field.”

OTHER RELATED COVERAGE

• In an episode of OncLive On Air, Patrick Y. Wen, MD, of Dana-Farber Cancer Institute and Harvard Medical School, discussed the significance of this accelerated approval across patient age groups, key efficacy and safety data that supported the decision, and the importance of biomarker testing in this population.
• In a past interview, Yoshie Umemura, MD, of Ivy Brain Tumor Center, further discussed the development of ONC201 in H3K27M-mutant diffuse midline glioma.
• In another OncLive On Air episode, Stephen Bagley, MD, MSCE, of Penn Medicine, spotlighted the exploration of ONC201 in the phase 3 ACTION trial (NCT05580562) in H3K27M-mutant diffuse midline gliomas and explained why clinicians should consider the trial for patients.
• This Clinical Trial Spotlight offers additional insight into the ACTION trial, in which dordaviprone aims to improve upon standard-of-care (SOC) radiotherapy in H3K27M-mutant glioma.
• In a past interview, Ashley Sumrall, MD, FACP, of Atrium Health Carolinas Medical Center and University of North Caroline at Chapel Hill, discussed the unmet needs for patients with gliomas, impacts that disease classification evolutions have had on diagnosis and management of the disease, and ongoing research with ONC201 in this area.
• Ilyas Sahin, MD, of the University of Florida College of Medicine, previously shared preclinical data from a study examining the combination of milademetan and ONC201 in solid tumors with MDM2 overexpression.

8/8: Zongertinib in Nonsquamous NSCLC With HER2 TKD Mutations

Indication: Accelerated approval was also awarded to zongertinib (Hernexeos) for the treatment of adult patients with unresectable or metastatic nonsquamous non–small cell lung cancer (NSCLC) harboring HER2 TKD-activating mutations, as detected by an FDA-approved test, after previous systemic therapy.

Supporting Data: The decision was supported by data from the phase 1 Beamion LUNG-1 trial (NCT04886804). Among evaluable patients who had received previous platinum-based chemotherapy without prior HER2-targeted TKIs or antibody-drug conjugates (ADCs; n = 71), the ORR was 75% (95% CI, 63%-83%) with a 6-month DOR rate of 58%. In patients previously treated with chemotherapy and a HER2-targeted ADC(n = 34), the ORR was 44% (95% CI, 29%-61%) and the 6-month DOR rate was 27%. Safety was manageable, with mostly grade 1/2 treatment-related adverse effects (TRAEs; diarrhea, 51%; rash, 27%); only 1 patient experienced a grade 3 or higher TRAE. No cases of treatment-related interstitial lung disease were reported.

Clinical Significance: Zongertinib provides an important new targeted therapy option for patients with HER2-mutant NSCLC, a population with historically limited treatment choices. The high response rates, particularly in those who had not previously received a HER2-directed agent, highlight the drug’s potential to redefine the treatment paradigm for this biomarker-driven subset. Its ongoing evaluation in the phase 3 Beamion LUNG-2 trial (NCT06151574) will clarify its role vs SOC regimens.

“It’s the first time that we’re seeing a HER2-targeting therapy that captures these most common exon 20 insertion mutations in HER2 with a specificity that doesn’t overlap with EGFR. We don’t see a lot of the on-target [adverse] effects [AEs] on the skin or in the gastrointestinal tract,” Martin F. Dietrich, MD, PhD, of The US Oncology Network Cancer Care Centers of Brevard and University of Central Florida College of Medicine, said in a recent interview.

ALSO APPROVED: The regulatory agency cleared the Oncomine™ Dx Target Test as a companion diagnostic for the identification of patients with unresectable or metastatic nonsquamous NSCLC whose tumors have HER2 TKD–activating mutations and could benefit from zongertinib.

OTHER RELATED COVERAGE

• In a recent OncLive On Air episode, Ticiana Leal, MD, of Emory University School of Medicine, and Misako Nagasaka, MD, PhD, of University of California, Irvine School of Medicine, discussed the significance of the approval, spotlighted key efficacy and safety data from Beamion LUNG-1, and unpacked where zongertinib currently fits into the paradigm.
• In the same month, the National Comprehensive Cancer Network updated their Clinical Practice Guideline in Oncology for the treatment of patients with NSCLC to include zongertinib tablets as a preferred subsequent therapy option for patients with advanced or metastatic HER2-mutant disease who have not previously received systemic therapy.
• Among the Clinical Trials to Watch in 2025, the phase 3 Beamion Lung-2 study (NCT06151574) is evaluating zongertinib vs with the KEYNOTE-189 (NCT02578680) regimen in patients with HER2-mutated NSCLC.
• In a previous interview, Joshua K. Sabari, MD, of New York University Grossman School of Medicine and Perlmutter Cancer Center, spotlighted key efficacy data from Beamion LUNG-1.
• John V. Heymach, MD, PhD, of The University of Texas MD Anderson Cancer Center, further discussed the potential role of zongertinib in HER2-mutated advanced NSCLC.
• For a Bridging the Gaps in Lung Cancer: 6-Month Update to the 2025 Winter Lung Cancer Conference, Benjamin P. Levy, MD, and Misty D. Shields, MD, PhD, explained how emerging data on novel HER2-targeted agents, such as zongertinib, show promise for advanced NSCLC.

8/29: 3-Month Version of Leuprolide Mesylate in Advanced Prostate Cancer

Indication: The FDA cleared a 3-month, 21-mg subcutaneous depot formulation of leuprolide mesylate (Camcevi ETM) for the palliative treatment of adult patients with advanced prostate cancer.

Supporting Data: The approval was supported by findings from a global, open-label, single-arm phase 3 trial (NCT03261999). In the intention-to-treat population (n = 144), 97.9% (95% CI, 93.5%-99.3%) of patients achieved the primary end point of sustained serum testosterone suppression to castration levels (≤50 ng/dL) by day 28 and maintained through day 168. Among evaluable patients (n = 143), 98.6% achieved castration by day 28, with a mean testosterone concentration of 17.8 ng/dL; no mean increase was observed following the second injection. Safety was manageable, with the most common AEs being hot flushing (24%), hypertension (11%), weight gain (8%), and injection site hemorrhage (6%).

Clinical Significance: This approval expands the Camcevi portfolio by offering a shorter 3-month dosing option alongside the 6-month, 42-mg formulation that was previously approved in 2021. The availability of multiple depot schedules provides greater flexibility in androgen deprivation therapy delivery, potentially improving convenience and alignment with patient and clinician treatment preferences in advanced prostate cancer management.

OTHER RELATED COVERAGE

• In January 2025, the regulatory agency issued a Day-74 letter stating that the Prescription Drug User Fee Act goal date for the marketing approval of the 3-month formulation of leuprolide mesylate for adult patients with advanced prostate cancer was August 29, 2025.
• The FDA received the 502(b)(2) new drug application seeking approval of the product in October 2024.
• In May 2021, the FDA had approved the 6-month subcutaneous depot formulation of leuprolide mesylate as a ready-to-use treatment for patients with advanced prostate cancer.

OTHER NOTEWORTHY DECISIONS

• 8/1: The FDA issued a complete response letter (CRL) to the supplemental biologics license application seeking the approval of daratumumab and hyaluronidase-fihj (subcutaneous daratumumab; Darzalex Faspro) in combination with bortezomib (Velcade), lenalidomide (Revlimid), and dexamethasone for use in adult patients with newly diagnosed multiple myeloma who are not eligible for or have deferred autologous stem cell transplant.
• 8/1: The regulatory agency also issued a CRL to the biologics license application seeking approval of odronextamab (Ordspono)for use in adult patients with relapsed or refractory follicular lymphoma who have received at least 2 prior lines of systemic therapy.
• 8/6: An intravenous (IV) formulation of tocilizumab-anoh (Avtozma), a biosimilar referencing IV tocilizumab (Actemra), was cleared for use in patients at least 2 years of age with CAR T-cell therapy–induced severe or life-threatening cytokine release syndrome.
• 8/20: The agency approved the MMR IHC Panel pharmDx (Dako Omnis) as a companion diagnostic to identify patients with mismatch repair–deficient colorectal cancer who may be eligible to receive nivolumab (Opdivo) as monotherapy or in combination with ipilimumab (Yervoy).