ASCO 2025丨Top 4 Most Viewed Abstracts

ASCO 2025 is about to start. Various abstracts are already available on the ASCO website. Four abstracts are listed at the top of the ASCO site and marked as the most viewed.

Zanidatamab

The abstract ranked first on the ASCO website is about the long-term results of zanidatamab treatment for gastroesophageal adenocarcinoma.

Zanidatamab is a HER2 bispecific antibody developed initially by Zymeworks and later licensed to Jazz Pharmaceuticals. It received accelerated FDA approval six months ago for treating biliary tract cancer (BTC).

This latest ASCO abstract discloses 4-year follow-up data from a phase 2 trial of zanidatamab combined with chemotherapy for HER2-positive advanced or metastatic gastroesophageal adenocarcinoma (mGEA). The trial aimed to evaluate the efficacy of zanidatamab plus chemotherapy as first-line (1L) treatment for mGEA.

A total of 46 patients were enrolled. As of July 28, 2024, the median follow-up was 48 months (range: 29-59). Results showed a median overall survival (OS) of 36.5 months, with the longest survival time being 57.9 months (no deaths at data cutoff).

Conclusion: After a median 4-year follow-up, zanidatamab plus chemotherapy as 1L treatment for HER2+ mGEA demonstrated clinically meaningful efficacy with durable responses and median OS over 3 years, with manageable safety. Additionally, early plasma ctDNA levels of zanidatamab plus chemotherapy in mGEA treatment were noted.

Notably, BeiGene acquired zanidatamab and ZW49 in 2018 for up to $400 million in milestone payments. BeiGene has submitted zanidatamab for marketing approval to the NMPA, which was accepted in June 2024.

PARP Inhibitor Talazoparib

Ranked second is the oral PARP inhibitor talazoparib combined with the AR inhibitor enzalutamide (TALA+ENZA) as first-line treatment for unselected metastatic castration-resistant prostate cancer (mCRPC) from the phase 3 TALAPRO-2 study.

The TALAPRO-2 trial met its primary endpoint, showing improved radiographic progression-free survival (rPFS) in patients with homologous recombination repair (HRR) gene mutations compared to placebo (PBO)+enzalutamide.

Data cutoff: In the TALA+ENZA and PBO+ENZA arms, 211 (52%) and 243 (60%) patients died, respectively, with median follow-up of 52.5 and 53.0 months.

The OS hazard ratio (HR) was 0.796 (95% CI, 0.661–0.958; 2-sided P=0.0155). Median OS was 45.8 months (39.4-50.8) vs. 37.0 months (34.1-40.4). Median rPFS was 33.1 months vs. 19.5 months (HR 0.667; 95% CI, 0.551–0.807; P<0.0001).

Conclusion: Compared with standard care, TALA+ENZA as 1L treatment in unselected HRR mCRPC patients offers statistically and clinically significant OS improvement and continued rPFS benefit.

KRAS G12D Inhibitor

The oral KRAS G12D inhibitor GFH375 from GENFLEET THERAPEUTICS is one of the hottest topics at ASCO, with its abstract pinned prominently on the ASCO site.

GFH375 is a KRAS G12D (ON/OFF) inhibitor that targets both activated and inactive forms of KRAS G12D protein. It directly inhibits the G12D-GTP complex and blocks its interaction with effector proteins like RAF, while also inhibiting GDP-GTP exchange to prevent activation.

The ASCO 2025 abstract presented preliminary data from the first-in-human phase I/II study of GFH375 in advanced solid tumors with KRAS G12D mutation, with data cutoff January 3, 2025, involving 32 patients.

In the 100 mg QD cohort, anti-tumor activity was observed. Among 22 patients evaluated after at least one treatment, objective response rate (ORR) was 27.3% (6/22), disease control rate (DCR) was 86.4% (19/22). Of 13 patients with stable disease (SD), 9 had tumor shrinkage.

In 7 pancreatic ductal adenocarcinoma (PDAC) patients, all showed tumor shrinkage: 3 partial responses (PR) and 4 SD. In 9 non-small cell lung cancer (NSCLC) patients, 3 PR, 5 SD, and 1 progressive disease (PD) were reported.

Safety: 8 patients (25%) experienced at least one grade 3/4 treatment-related adverse event (TRAE), no grade 5 TRAE; 5 (15.6%) had serious adverse events; 8 (25%) discontinued treatment, 2 (6.3%) due to treatment-emergent adverse events (TEAE). Most common TRAEs were gastrointestinal and grade 1-2.

The study reports that GFH375 monotherapy showed good tolerability and promising anti-tumor activity in advanced solid tumors, supporting further clinical development.

Menin Inhibitor

Another focus is the abstract on Ziftomenib, a highly selective, once-daily oral menin inhibitor targeting the interaction between menin and the KMT2A/MLL protein complex. It is being developed for AML patients with specific gene mutations and high unmet need.

This ASCO abstract reported early analysis results from the pivotal phase 1b/2 KOMET-001 study of Ziftomenib in relapsed/refractory NPM1-mutated acute myeloid leukemia (AML).

Results showed the phase 2 primary endpoint was met. Across phase 1b/2, complete remission (CR)/CR with partial hematologic recovery (CRh) rate was 25% (28/112; 95% CI 17–34); overall response rate was 35% (39/112; 95% CI 26–44).

In phase 2, CR/CRh rate was 23% (21/92; 95% CI 15–33); among responders, 67% (10/15) were minimal residual disease (MRD) negative.

Based on positive clinical results, the developer Kura Oncology and Kyowa Kirin plan to submit an NDA to the US FDA in Q2 2025.