The Targeted Pulse: ASCO GU and FDA Decisions

Welcome to this week’s edition of The Targeted Pulse, our top 5 stories of the week delivered right to you. This week, we saw ASCO GU 2026 previews and FDA decisions in lung, breast, and colorectal cancers. From FDA decisions to expert clinical insights, here are the stories that shaped this week.

ASCO GU 2026 Preview: Highlights of Key Trials in Bladder, Kidney, Prostate, and Rare Cancers

The ASCO GU 2026 Symposium highlights a transformative shift toward earlier, biomarker-driven interventions across genitourinary cancers. A major focus is the KEYNOTE-B15 trial, which positions enfortumab vedotin (Padcev) and pembrolizumab (Keytruda) as a potential new standard for muscle-invasive bladder cancer (MIBC), challenging traditional cisplatin-based regimens.

In prostate cancer, the PSMA addition and PEACE-2 trials explore moving radioligand and intensive therapies into earlier treatment lines. Kidney cancer research emphasizes the LITESPARK program, evaluating belzutifan (Welireg) combinations to improve survival. Additionally, rare cancer discussions include using biomarkers like miR-371a-3p for risk stratification, signaling a broader era of precision oncology and "dynamic surveillance" using circulating tumor DNA.

FDA Fast Tracks Novel Inhibitor for BRCA-Mutant Breast Cancer

The FDA has granted fast track designation to ART6043, a first-in-class oral inhibitor of DNA polymerase theta (Polθ), for treating germline BRCA-mutated, HER2-negative advanced or metastatic breast cancer. Developed by Artios Pharma, ART6043 targets the microhomology-mediated end-joining (MMEJ) pathway, inducing "synthetic lethality" in BRCA-deficient cells.

Preliminary data from a phase 1/2a study presented at ESMO 2025 showed a favorable safety profile and early antitumor activity when combined with the PARP inhibitor olaparib (Lynparza). This designation aims to accelerate the development of ART6043 as a strategy to overcome or delay treatment resistance in patients with high unmet needs.

FDA Grants Accelerated Approval to Zongertinib for HER2-Mutant NSCLC

The FDA granted accelerated approval to zongertinib (Hernexeos) for adult patients with unresectable or metastatic, nonsquamous non–small cell lung cancer harboring HER2 tyrosine kinase domain activating mutations. This decision expands the agent's indication to include treatment-naive patients, building upon its August 2025 approval for previously treated disease.

The approval was supported by the Beamion LUNG-1 trial, where frontline zongertinib demonstrated a 76% objective response rate. As an oral, irreversible HER2-selective inhibitor, zongertinib offers a new standard of care with a manageable safety profile, though warnings include hepatotoxicity and interstitial lung disease.

2026 ASCO GU Highlights: Bladder Cancer KEYNOTE-B15

At the 2026 ASCO GU Cancers Symposium, results from the phase 3 KEYNOTE-B15 (EV-304) trial will be presented as a landmark study for MIBC. The trial evaluated perioperative enfortumab vedotin plus pembrolizumab against the long-standing standard of care, gemcitabine plus cisplatin.

Results demonstrated a transformative shift, with the combination significantly improving event-free survival (EFS), overall survival (OS), and pathologic complete response rates in cisplatin-eligible patients. With a hazard ratio for EFS of approximately 0.4, this "chemo-free" regimen challenges 20 years of cisplatin dominance, potentially establishing a new frontline standard that moves potent antibody-drug conjugate and immunotherapy combinations into earlier, curative-intent settings.

FDA Grants Encorafenib Combo Traditional Approval in BRAF V600E+ mCRC

The FDA granted traditional approval to encorafenib (Braftovi) in combination with cetuximab and fluorouracil-based chemotherapy (mFOLFOX6 or FOLFIRI) for adult patients with treatment-naive, BRAF V600E-mutant metastatic colorectal cancer. This decision converts the accelerated approval granted in December 2024.

The approval is supported by the phase 3 BREAKWATER trial, where the encorafenib triplet significantly improved outcomes compared with standard chemotherapy. Key results included a median progression-free survival of 12.8 months vs 7.1 months and a median OS of 30.3 months vs 15.1 months. This regimen establishes a new first-line targeted standard for this aggressive, poor-prognosis molecular subset.