The 2025 AACR Annual Meeting delivered several notable developments in precision oncology and immunotherapy.
Much of the attention centered on non-small cell lung cancer (NSCLC) and mismatch repair-deficient (MMRd) tumors, reflecting a clear shift toward biomarker-driven treatment and earlier intervention.
For biopharma teams involved in early-stage development, lifecycle planning, or competitive positioning, these findings are especially relevant.
Opus Strategy attended AACR in San Diego to analyze key readouts, speak with cross-functional leaders, and assess what matters most for strategic decision-makers.
Below are five takeaways we believe should be top-of-mind.
Long considered one of the most difficult oncology targets, KRAS G12D now has its first clinical validation.
RMC-9805 (zoldornasib) produced a 61% overall response rate and 89% disease control rate in previously treated NSCLC patients with this mutation. The drug showed encouraging tolerability and clear on-target activity.
This opens the door to expansion into other G12D-mutant tumors such as pancreatic and colorectal cancers. As the KRAS space becomes more defined by submutation, teams will need to rethink trial segmentation, portfolio prioritization, and positioning against other KRAS-directed therapies.
KRAS G12C inhibitors like sotorasib and adagrasib have reached the market, but G12D has remained elusive due to structural features that limit drug binding.
Zoldornasib represents a new class of KRAS inhibitors that may overcome those barriers through allele-specific targeting, creating new competitive dynamics across multiple tumor types.
The AENEAS-2 trial presented new data on combining aumolertinib—a third-generation EGFR TKI—with chemotherapy in first-line EGFR-mutant NSCLC.
The combination extended median progression-free survival (PFS) to 28.9 months, compared to 18.9 months with TKI alone. Overall survival data remains immature, but the early trend is favorable.
This raises important questions for clinical teams that have traditionally focused on monotherapy strategies. Combination regimens may recalibrate expectations around first-line durability and resistance management.
Although osimertinib remains the standard of care globally, regional access and pricing differences influence treatment decisions. Aumolertinib, already approved in China, has the potential for broader adoption if confirmatory data holds up internationally.
The targeted HER2 inhibitor Zongertinib showed promising early data in HER2-mutant NSCLC. The drug demonstrated antitumor activity and a favorable safety and tolerability profile in this genetically defined subgroup.
Although HER2-mutant NSCLC is a relatively small population, it is increasingly seen as an actionable target beyond breast and gastric cancers. Development programs already active in HER2 may now consider NSCLC as a logical extension.
Trastuzumab deruxtecan (T-DXd) is already approved for this indication, and while its overall safety profile has been described as manageable, interstitial lung disease (ILD) remains a key risk.
In clinical trials, ILD was found in up to 28% of patients and in rare cases can be fatal. Small molecule inhibitors like zongertinib may offer a more favorable risk profile if CNS activity is confirmed in future studies.
JYP0322, a novel ROS1 inhibitor, posted an 85.7% response rate in ROS1 TKI-naïve patients and 54.5% in those who had received two or more lines of systemic therapy. The drug also showed CNS activity (a key feature for patients with brain metastases) and maintained a strong tolerability profile.
With several ROS1 inhibitors on the market, CNS penetration and durability of response are critical differentiators. Agents without CNS data will face steeper challenges in both positioning and reimbursement.
Crizotinib’s limited CNS penetration has raised concerns about its suitability for long-term management. This is particularly true for patients with brain metastases, where next-generation ROS1 inhibitors show improved durability and CNS activity.
Neoadjuvant immunotherapy, which involves giving checkpoint inhibitors before surgery, is redefining the standard of care for mismatch repair-deficient (MMRd) tumors.
The approach gained attention following a 2022 study from Memorial Sloan Kettering (MSK), where all patients with early-stage MMRd rectal cancer achieved a complete response and were able to avoid both chemoradiation and surgery.
AACR 2025 data from an expanded cohort, now including MMRd tumors like endometrial and gastric cancers, support earlier use of checkpoint inhibitors in biomarker-selected patients.
As the data matures, clinical teams may need to reassess trial design, timing, and sequencing strategies. The conversation is shifting from whether the approach works to how early it should be introduced and in which settings surgery can be safely avoided.
AACR 2025 reinforced several trends in solid tumor oncology.
Precision targeting is progressing in rare subtypes, combination therapy is advancing in key populations, and early-line immunotherapy is prompting new standards in curative settings.
These shifts have implications for R&D strategy, lifecycle planning, and competitive positioning. For executive teams guiding oncology pipelines, agility in both development and messaging will be essential.
At Opus Strategy, we partner with clinical and commercial leaders to translate emerging data into meaningful strategy. Whether you’re preparing to expand an indication, evaluate new development pathways, or refine your go-to-market approach, we help align science with business priorities.
To explore how AACR 2025 developments may impact your pipeline or planning, reach out to Opus Strategy for a tailored discussion today.