May 2026 proved to be one of the most consequential months of the year for oncology regulators, with the FDA issuing 8 oncology and hematology approvals spanning breast cancer, bladder cancer, hematologic malignancies, and rare solid tumors. The month opened with a historic milestone—the first-ever FDA approval of a PROTAC (proteolysis-targeting chimera) in any indication—and closed with a novel antibody-drug conjugate for an ultra-rare blood cancer. Below is a glance at every key action from the month.
May 2026 FDA Approvals
Drug: Vepdegestrant (Veppanu)
Mechanism: Heterobifunctional protein degrader (PROTAC)
Indication: Adults with estrogen receptor (ER)-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer, with disease progression following at least 1 prior line of endocrine therapy, as detected by an FDA-authorized test
The FDA granted approval to vepdegestrant, marking a landmark moment as the first PROTAC approved in any indication. PROTACs are a novel class of heterobifunctional molecules that harness the cell's own ubiquitin-proteasome system to degrade target proteins, rather than merely inhibit them. Vepdegestrant targets and degrades the estrogen receptor, offering a distinct mechanism compared with selective estrogen receptor degraders (SERDs) or modulators already in clinical use.
The approval was based on the phase 3 VERITAC-2 trial (NCT05654623), a randomized, open-label, active-controlled, multicenter study enrolling 624 patients, including 270 with ESR1-mutated tumors. The FDA also approved the Guardant360 CDx as a companion diagnostic to identify eligible patients harboring ESR1 mutations.
Drug: Zenocutuzumab-zbco (Bizengri)
Mechanism: Bispecific anti-HER2/HER3 antibody
Indication: Adults with advanced, unresectable, or metastatic cholangiocarcinoma harboring a neuregulin 1 (NRG1) gene fusion with disease progression on or after prior systemic therapy
The FDA approved zenocutuzumab for NRG1 fusion-positive cholangiocarcinoma, the first drug approved for this population. NRG1 gene fusions are an extremely rare, oncogenic driver occurring across multiple tumor types; cholangiocarcinoma represents one of the most underserved subsets. Zenocutuzumab works by blocking the NRG1 ligand from binding to HER3, thereby interrupting downstream oncogenic signaling.
ADC dominance continues. Three of May's oncology approvals involved antibody-drug conjugates—T-DXd (HER2-targeted), Dato-DXd (TROP2-targeted), and pivekimab sunirine (CD123-targeted)—underscoring the continued maturation of the ADC platform across tumor types and target classes.
A PROTAC era begins. Vepdegestrant's approval marks a turning point for targeted protein degradation as a drug class. Unlike small-molecule inhibitors, PROTACs catalytically eliminate their target protein, potentially overcoming resistance mechanisms driven by target overexpression or mutation.
Bladder cancer momentum. May saw 2 bladder cancer approvals —atezolizumab for ctDNA MRD-positive adjuvant MIBC and durvalumab + BCG for BCG-naive high-risk NMIBC—continuing a robust streak of regulatory activity in urothelial malignancies that has spanned the past several years.
Rare disease focus. Zenocutuzumab for NRG1+ cholangiocarcinoma and pivekimab sunirine for BPDCN highlight the FDA's ongoing commitment to rare and ultra-rare oncologic indications, each representing the first approval in its respective molecular or disease subtype.
Approval was supported by a single-arm trial enrolling 19 patients with NRG1 fusion-positive cholangiocarcinoma; the overall response rate was 36.8%, with duration of response ranging from 2.8 to 12.9 months. The agency had previously granted the drug breakthrough therapy and orphan drug designations for this indication.
Drug: Oral decitabine and cedazuridine tablets (Inqovi) in combination with venetoclax (Venclexta)
Mechanism: Oral hypomethylating agent + BCL2 inhibitor combination
Indication: Newly diagnosed acute myeloid leukemia (AML) in adults aged 75 years or older, or in adults with comorbidities that preclude intensive induction chemotherapy
The FDA approved an all-oral regimen for treatment-ineligible patients with newly diagnosed AML, combining decitabine and cedazuridine—already approved for myelodysplastic syndrome and chronic myelomonocytic leukemia—with the BCL2 inhibitor venetoclax. The transition from intravenous or subcutaneous hypomethylating agents to a fully oral backbone represents a meaningful quality-of-life advance for an elderly patient population, reducing infusion center burden.
Approval was based on Study ASTX727-07, a single-arm, open-label trial evaluating the combination in 101 adults with newly diagnosed AML who were 75 or older or had comorbidities precluding intensive chemotherapy. The FDA granted orphan drug designation to decitabine/cedazuridine for this AML indication.
Drug: Sonrotoclax (Beqalzi)
Mechanism: BCL2 inhibitor
Indication: Adults with relapsed or refractory mantle cell lymphoma (MCL) after at least 2 prior lines of systemic therapy, including a Bruton tyrosin kinase (BTK) inhibitor
The FDA granted accelerated approval to sonrotoclax, a next-generation BCL2 inhibitor, for heavily pretreated MCL. The approval addresses a significant unmet need in patients who have progressed through both anti-CD20-based therapy and a BTK inhibitora population with limited options.
Approval was supported by BGB-11417-201 (NCT05471843), a single-arm, multicenter trial evaluating efficacy in 103 adults with relapsed or refractory MCL who had previously received anti-CD20 therapy and a BTK inhibitor. Continued approval may be contingent upon verification of clinical benefit in a confirmatory trial.
Drug: Fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu)
Mechanism: HER2-directed antibody-drug conjugate (ADC)
Indications (two):
- Neoadjuvant: T-DXd followed by taxane, trastuzumab, and pertuzumab (THP) for adults with HER2-positive (IHC 3+ or ISH+) stage II or III breast cancer
- Adjuvant: T-DXd for adults with HER2-positive breast cancer with residual invasive disease after neoadjuvant treatment with trastuzumab (±pertuzumab) and taxane-based therapy
The FDA approved 2 separate new indications for T-DXd in the early-stage HER2-positive breast cancer setting, extending the reach of this ADC from its well-established metastatic indications into curative-intent treatment. The ADC uses a cleavable linker and a topoisomerase I inhibitor payload with a high drug-to-antibody ratio, delivering potent cytotoxic activity to HER2-expressing tumor cells.
The neoadjuvant approval was based on DESTINY-Breast11 (NCT07239271), a randomized, 3-arm, open-label, multicenter trial of 927 adults with HER2-positive, high-risk, early-stage breast cancer. The adjuvant approval was based on DESTINY-Breast05 (NCT04622319), a randomized, 2-arm, open-label, multicenter trial of 1635 adults with residual invasive disease after neoadjuvant therapy.
Drug: Atezolizumab (Tecentriq) and atezolizumab/hyaluronidase-tqjs (Tecentriq Hybreza)
Mechanism: PD-L1 immune checkpoint inhibitor
Indication: Adjuvant treatment of adults with muscle invasive bladder cancer (MIBC) after cystectomy who have circulating tumor DNA molecular residual disease (ctDNA MRD), as detected by an FDA-authorized test
This approval represents a significant step forward for biomarker-guided bladder cancer management, as it is among the first approvals to use ctDNA MRD status rather than pathologic staging alone to select patients for adjuvant immunotherapy after radical cystectomy. Patients who are ctDNA MRD-positive face a substantially elevated recurrence risk, and this indication provides them with an evidence-based therapeutic option.
Drug: Datopotamab deruxtecan-dlnk (Dato-DXd; Datroway)
Mechanism: TROP2-directed ADC
Indication: Adults with unresectable or metastatic triple-negative breast cancer (TNBC) who are not candidates for PD-1/PD-L1 inhibitor therapy
The FDA approved Dato-DXd for a new patient subset in TNBC, specifically those who are not candidates for immunotherapy: an underserved group given the field's heavy reliance on checkpoint inhibitors. This TROP2-directed ADC links a topoisomerase I inhibitor payload to a TROP2 antibody, exploiting the high expression of Trop-2 in TNBC tumor cells.
Approval was based on TROPION-Breast02 (NCT05374512), a multicenter, open-label, randomized trial of 644 patients with unresectable or metastatic TNBC. Dato-DXdhad previously received approvals in HR-positive/HER2-negative metastatic breast cancer (January 2025) and EGFR-mutated NSCLC (June 2025), making this its third oncology indication.
Drug: Pivekimab sunirine-pvzy (Decnupaz)
Mechanism: CD123-directed antibody and alkylating agent conjugate
Indication: Adults with blastic plasmacytoid dendritic cell neoplasm (BPDCN)
The FDA approved pivekimab sunirine for BPDCN, an ultra-rare and aggressive hematologic malignancy arising from plasmacytoid dendritic cell precursors and characterized by CD123 overexpression. With very few approved treatment options for BPDCN, this approval addresses a critical gap for a disease that frequently presents in older patients and carries a poor prognosis.
Pivekimab sunirine delivers an alkylating payload directly to CD123-expressing leukemic cells, combining targeted precision with cytotoxic potency.
Drug: Durvalumab (Imfinzi)
Mechanism: PD-L1 immune checkpoint inhibitor
Indication: Adults with Bacillus Calmette Guérin (BCG)-naive, high-risk non–muscle invasive bladder cancer (NMIBC), in combination with BCG
Closing the month, the FDA approved durvalumab in combination with BCG for BCG-naive, high-risk NMIBC. BCG, an intravesical immunotherapy, has been the standard of care for high-risk NMIBC for decades, but recurrence rates remain substantial and options after BCG failure are limited. Adding durvalumab to the BCG backbone in the frontline naive setting represents a potential new standard aimed at improving durable response rates.
