Key 2025 ASCO® Themes to Expect

With the 2025 ASCO® Annual Meeting around the corner, oncology’s innovation engine has never been more powerful. At Putnam, we’re looking to the 2025 ASCO® Annual Meeting for clarity on critical debates – and will be tracking the following emerging themes that will define the next standard of care.

Taking Immunotherapies Earlier in Cancer Care

PD-(L)1i’s are emerging as the cornerstone of treatment in several non-metastatic solid cancers; the risk-benefit trade-off becomes even more important in these populations, and every immune maneuver must earn its place, and increasingly so in sub-populations that actually benefit from it.

What to Expect

1. Optimizing Adjuvant ICI Use (MATTERHORN, NIVOPOSTOP, ATOMIC):

• Which molecular and clinical features reliably guide decisions on the need for adjuvant immunotherapy or identify patients who may benefit from intensified ICI strategies?

2. Leveraging ctDNA in the Peri-Operative Setting (NIAGARA):

• How does ctDNA analysis refine peri-operative ICI treatment strategies, and what potential risks should be considered?

3. Predicting Durable Responses in Locally Advanced Setting (ADRIATIC):

• Which molecular and clinical markers best predict long-lasting responses to immune checkpoint inhibitors (ICIs), enabling more precise treatment decisions?

4. Patient Selection & Organ Preservation (SURE-02):

• How can we reliably identify patients who, after neoadjuvant immunotherapy, could safely delay radical cystectomy—and for how long?

Bottlenecks to Cell Therapy Success in Solid Tumors

Expanding cell therapies beyond hematologic cancers is limited by tumor heterogeneity, specificity, immunosuppression, and cell activation hurdles. Incremental CAR-T advancements are underway, but the current clinical evidence suggests it may be a long road towards truly transforming outcomes in solid tumors.

What to Expect

1. Armored CAR-T Cells and Immunosuppression

• Will Legend’s DLL-3 CAR-T, armored to counteract TGFβ-driven suppression, validate its therapeutic hypothesis in the clinic?

2. Logic-Gated CAR-T and On-target, Off-tumor Toxicity

• Can dual logic-gated CARs effectively and selectively target cancer cells expressing MSLN and exhibiting loss of heterozygosity (LOH)?

3. Innovations Enhancing CAR-T Activation and Persistence

• Can coupled CAR-T therapies targeting GCC and CD19, enhanced by cytokine release, demonstrate clinical proof-of-concept? What challenges remain?
• Will Ori-cell’s armored, next-generation GPC3 CAR-T translate molecular innovations into improved T-cell activation and persistence clinically?

4. Dual-Targeting CAR-T to Tackle Tumor Heterogeneity

• Does dual targeting of EGFR and IL13Ra2 effectively overcome tumor heterogeneity and antigen escape in glioblastoma (GBM)?

KRAS – Undruggable to Druggable

Covalent KRASG12C inhibitors marked a breakthrough in a hard-to-treat sub-population; both allele-specific and pan-RAS strategies continue to make inroads into broader populations and tumors beyond NSCLC, using novel platforms. However, challenges such as drug resistance, toxicity with combinations and need for broader mutation coverage remain.

What to Expect

1. Next-Generation KRASG12C Inhibitors and Combination Approaches:

• What is the strength of competitive differentiation of the next gen KRASG12C inhibitors vs 1^st gen G12Ci, based on available clinical evidence in NSCLC and CRC?
• Does integration of next gen G12Ci with PD-(L)1i or targeted approaches (e.g. FAK inhibitors, EGFR inhibitors) enhance efficacy, delay resistance, and broaden patient applicability?

2. Relevant Sub-Populations to Optimize Effectiveness:

• Will negative selection of biomarkers such as lipid metabolic gene expression profiles (e.g., KRAS-STK11 in NSCLC) help further optimize effectiveness?

3. Novel Therapeutic Modalities and Platforms:

• What are the key value drivers of the innovative KRAS targeting modalities – protein degraders, KRAS targeting vaccines, T-cell receptor (TCR)-based therapies specifically engineered against KRAS G12V mutations?

As the 2025 ASCO® Annual Meeting unfolds, stay tuned for our insights on how the oncology industry can navigate these transformational shifts in treatment paradigms.

We’ll be attending alongside our Inizio colleagues at booth 10108 – stop by to learn more.

References

1. Punekar et al, Abstract #3040, presented at the 2025 ASCO® Annual Meeting
2. Sands et al, Abstract #8104, presented at the 2025 ASCO® Annual Meeting
3. Fan et al, Abstract #4084, presented at the 2025 ASCO® Annual Meeting
4. Bagley et al, Abstract #102, presented at the 2025 ASCO® Annual Meeting
5. Schlechter et al, Abstract #3581, presented at the 2025 ASCO® Annual Meeting
6. Liang et al, Abstract #TPS2699, presented at the 2025 ASCO® Annual Meeting
7. Liang et al, Abstract #TPS2698, presented at the 2025 ASCO® Annual Meeting
8. Sen et al, Abstract #TPS3178, presented at the 2025 ASCO® Annual Meeting
9. Fu et al, Abstract #3083, presented at the 2025 ASCO® Annual Meeting
10. Hollebecque et al, Abstract #3507, presented at the 2025 ASCO® Annual Meeting
11. Lugowska et al, Abstract #3508, presented at the 2025 ASCO® Annual Meeting
12. Song et al, Abstract #8629, presented at the 2025 ASCO® Annual Meeting
13. Skoulidis et al, Abstract #TPS8656, presented at the 2025 ASCO® Annual Meeting
14. Solomon et al, Abstract #TPS8649, presented at the 2025 ASCO® Annual Meeting
15. Pothen et al, Abstract #8534, presented at the 2025 ASCO® Annual Meeting
16. Wolpin et al, Abstract #TPS4230, presented at the 2025 ASCO® Annual Meeting
17. Basu et al, Abstract #TPS2678, presented at the 2025 ASCO® Annual Meeting
18. Ai et al, Abstract #3013, presented at the 2025 ASCO® Annual Meeting
19. Jänne et al, Abstract #8500, presented at the 2025 ASCO® Annual Meeting