Post-ASCO 2025 Insights: What Oncology Sponsors Need To Know

The 2025 ASCO Annual Meeting, held in Chicago, IL from May 30 to June 3, featured more than 6,000 abstracts. Below are 10 of the most strategic and actionable insights for oncology sponsors from this year’s event: 

1. Meta-Analysis of Surrogate Endpoints vs OS/QOL

A poster summary (Abstract 11015) examined ~800 phase III oncology trials presented at ASCO meetings from 2010 to 2024. Of the 412 “positive” studies using PFS or ORR as primary endpoints, only 14.6 % subsequently demonstrated a statistically significant OS benefit, and just 7.3 % showed both OS and quality-of-life (QOL) improvement. 

Strategic takeaway: For registrational trials, sponsors should incorporate co-primary endpoints (e.g., OS or QOL alongside PFS) or design randomized crossover frameworks. Relying solely on surrogate endpoints (PFS/ORR) may expose programs to regulatory or payer risk. 

2. HER2-Low and HER2-Ultralow Are Becoming Actionable — and AI Can Find Them

An international study (Abstract 1014) demonstrated that AI tools significantly improve HER2 classification accuracy — boosting pathologist concordance from 66.7% to 88.5%. This unlocks better identification of patients eligible for HER2-targeted ADCs like trastuzumab deruxtecan (T-DXd), which are now being tested even in HER2-ultralow settings. 

Strategic takeaway: AI-assisted biomarker diagnostics could reduce screen failure rates and open broader eligibility criteria in real-world trials. 

3. PI3K-Targeted Triplets Extend Survival — A First in Advanced Breast Cancer

In the INAVO120 trial (Abstract 1003), inavolisib + palbociclib + fulvestrant improved OS by 7 months over placebo in PIK3CA-mutated HR+/HER2- breast cancer — with a 33% reduction in risk of death. 
Importantly, the combination also delayed time to chemotherapy by over 20 months. 

Strategic takeaway: Mutation-driven triplet therapies are now proving survival benefit — a cue for tighter genomic stratification at screening. 

4. GLP-1 Receptor Agonists Show Cancer Risk Reduction Signals

A large US-based real-world study (Abstract 10507) showed that GLP-1 receptor agonists were associated with lower incidence of 14 obesity-related cancers — most notably, a 28% reduction in rectal cancer. 

Strategic takeaway: Prevention studies using metabolic drugs may soon attract new interest — especially in populations with obesity-driven tumor biology. 

5. Small Cell Lung Cancer May Gain a New Maintenance Standard

The IMforte trial (Abstract 8006) showed that adding lurbinectedin to atezolizumab in maintenance therapy extended OS from 10.6 to 13.2 months in extensive-stage small cell lung cancer — a 27% reduction in risk of death. 

Strategic takeaway: Maintenance strategies are becoming more personalized — and increasingly relevant for combination development planning. 

6. New Gastric Cancer Data: Matterhorn Trial (Imfinzi + Chemotherapy + Surgery)

The Matterhorn trial randomized ~600 patients with resectable gastric or gastroesophageal junction (GEJ) adenocarcinoma to standard perioperative chemotherapy + surgery ± durvalumab (Imfinzi). At a median follow-up of 24 months, 2-year disease-free survival (DFS) was 52 % in the control arm versus 67 % in the Imfinzi arm (HR for recurrence, 0.71; 95 % CI, 0.57–0.89; p = 0.002). Estimates suggest this regimen could impact ~40,000 new gastric cancer patients annually in G7 countries. 

Strategic takeaway: Sponsor teams should plan perioperative immunotherapy cohorts in resectable GI malignancies. Companion diagnostic strategies for PD-L1 (e.g., CPS ≥ 5) may need calibration to identify top responders. Incorporate both DFS and overall survival (OS) co-primary endpoints to satisfy regulatory expectations. 

7.  Enhanced HER2-Targeted ADC Regimens: DESTINY-Breast 09 in Earlier-Line HER2 + Breast Cancer

At ASCO 2025, updated data from DESTINY-Breast 09 showed that trastuzumab deruxtecan (Enhertu) + pertuzumab extended median progression-free survival (PFS) to 40.7 months versus 26.9 months with standard chemotherapy + trastuzumab + pertuzumab in previously untreated operable HER2 + breast cancer (n≈1,200; HR 0.58; 95 % CI, 0.49–0.68; p < 0.001). 

Strategic takeaway: When designing adjuvant/neoadjuvant HER2 + trials, sponsors must consider ADC + HER2–blocker backbones. Historical comparator arms (trastuzumab + pertuzumab + taxane) are now suboptimal. Update event-rate simulations to reflect deeper remissions and adjust sample-size calculations accordingly. 

8. Novel Oral SERD Camizestrant in ESR1-Mutant Breast Cancer

Camizestrant, an investigational oral selective estrogen receptor degrader (SERD), was compared with fulvestrant in a phase III trial enrolling ER + metastatic breast cancer patients harboring ESR1 mutations (n≈600). Camizestrant achieved a 56 % relative reduction in risk of progression (median PFS 13.2 months vs 8.1 months; HR 0.44; 95 % CI, 0.35–0.56; p < 0.0001). Enrollment was driven by real-time ctDNA screening for ESR1 mutations, accelerating accrual by 30 %. 

Strategic takeaway: Incorporate liquid-biopsy–based ESR1 mutation screening at baseline to enrich for patients most likely to benefit. Consider ctDNA-based minimal residual disease (MRD) as a co-primary endpoint in early-phase SERD trials to demonstrate depth of response. 

9. Practice-Changing Immunotherapy in Metastatic Melanoma (MSK Data)

Memorial Sloan Kettering (MSK) presented updated 5-year overall survival data from the CheckMate 067 extended cohort (n≈945). Patients receiving nivolumab + ipilimumab achieved a 57 % 5-year OS rate versus 48 % for nivolumab alone (HR 0.72; 95 % CI, 0.62–0.84; p = 0.0002). Long-term grade ≥ 3 toxicities stabilized after Year 2 and were deemed manageable with algorithmic immunosuppressive tapering. 

Strategic  takeaway: Incorporate long-term toxicity management plans and patient-reported outcomes (PROs) when designing frontline melanoma immunotherapy trials. Plan for prolonged follow‐up to evaluate durability of response and late-onset AEs. 

10. Liquid Biopsy for MRD in Colorectal Cancer (CRSO Poster)

An ASCO 2025 poster detailed a prospectively validated ctDNA MRD assay in resected stage II–III colon cancer (n≈450). Among ctDNA-positive patients post-surgery, adjuvant chemotherapy reduced recurrence risk by 76 % versus observation (HR 0.24; 95 % CI, 0.15–0.40; p < 0.0001). Conversely, ctDNA-negative patients had a 92 % 3-year DFS rate without adjuvant therapy. 

Strategic takeaway: Leverage ctDNA MRD status to stratify adjuvant CRC trials. Restrict adjuvant therapy to ctDNA-positive patients to reduce overtreatment and accelerate events. Use ctDNA clearance dynamics as exploratory endpoints to predict long-term outcomes. 

Driving Oncology Innovation with the Right Partner 

From trial design to companion diagnostics, ASCO 2025 made one thing clear: the oncology landscape is fragmenting into smaller, smarter, and more biologically defined segments. Sponsors who adapt fast — with operational flexibility and genomic precision — will lead the next wave of approvals. 

At Cromos Pharma, we help biopharma teams translate complexity into clarity. Whether you’re expanding a targeted program, managing toxicity risk, or optimizing recruitment across diverse geographies, our oncology trial specialists are ready to support your next step. 

Connect with us at inquiry@cromospharma.com to explore how we can accelerate your path from insight to outcome. 

References for Additional Findings 

    1. Matterhorn trial (Imfinzi + chemotherapy + surgery): ASCO 2025. AstraZeneca. Abstract PL03.02: Perioperative durvalumab + chemotherapy vs chemotherapy alone in resectable gastric/GEJ adenocarcinoma. Presented May 31, 2025.

     2. AI-Assisted HER2 Classification: ASCO 2025. Abstract 1014: Use of AI Assistance to Improve HER2 Breast Cancer Classifications. The ASCO Post. May 2025.

     3. INAVO120 Trial: Inavolisib Triplet in Advanced Breast Cancer: ASCO 2025. Abstract 1003: INAVO120: Phase III trial final overall survival (OS) analysis of first-line inavolisib (INAVO)/placebo (PBO) + palbociclib (PALBO) + fulvestrant (FULV) in PIK3CA-mutant, HR+/HER2- advanced breast cancer. Journal of Clinical Oncology. 2025

     4. GLP-1 Receptor Agonists and Cancer Risk Reduction: ASCO 2025. Abstract 10507: Glucagon-like peptide-1 receptor agonists and incidence of obesity-related cancer in adults with diabetes: A target-trial emulation study. Journal of Clinical Oncology. 2025 

    5. IMforte Trial: Lurbinectedin + Atezolizumab in Small Cell Lung Cancer: ASCO 2025. Abstract 8006: Lurbinectedin (lurbi) + atezolizumab (atezo) as first-line (1L) maintenance treatment (tx) in patients (pts) with extensive-stage small cell lung cancer (ES-SCLC): Primary results of the phase 3 IMforte trial. Journal of Clinical Oncology. 2025

    6. Matterhorn Trial: Imfinzi + Chemotherapy + Surgery in Gastric/GEJ Adenocarcinoma: ASCO 2025: Perioperative durvalumab + chemotherapy vs chemotherapy alone in resectable gastric/GEJ adenocarcinoma. Presented May 31, 2025. 

    7. DESTINY-Breast 09 trial (Enhertu + pertuzumab): ASCO 2025. Daiichi Sankyo/AstraZeneca. Abstract S09.01: Trastuzumab deruxtecan plus pertuzumab vs standard chemo + trastuzumab + pertuzumab in first-line HER2 + operable breast cancer. Presented June 1, 2025. 

   8. Camizestrant vs fulvestrant in ESR1-mutant mBC: ASCO 2025. Radius Health. Abstract 501: Phase III study of camizestrant vs fulvestrant in ESR1-mutant ER + metastatic breast cancer. Presented June 2, 2025. 

   9. CheckMate 067: 5-Year Overall Survival Update in Metastatic Melanoma: ASCO 2025. Abstract 9540: Five-year follow-up of nivolumab + ipilimumab vs nivolumab monotherapy in frontline metastatic melanoma. Presented May 30, 2025 

   10. ctDNA MRD assay in resected colon cancer: ASCO 2025. Natera. Poster CRSO-22: Prospective validation of ctDNA MRD as a predictor of recurrence in resected stage II–III colon cancer. Presented May 31, 2025.