What to Watch Out for at ASCO GI 2025: Key Abstracts for Community Oncologists

GI Cancer and ctDNA : © SciePro - stock.adobe.com

As the 2025 American Society of Clinical Oncology Gastrointestinal Cancers (ASCO GI) Symposium approaches, community oncologists can expect a wealth of new data that may shape the future of GI cancer treatment.

“There is a lot of investigation going on, not only related to the development of new compounds, targeting different pathways…but also in the identification of patients who benefit more or less from available therapies,” explained Bruno Sangro MD, PhD, head of Hepatology Unit, Internal Medicine Department, Clinica Universidad de Navarra, in an interview with Targeted Oncology^TM regarding the ASCO GI Symposium.

Here are several of the most anticipated abstracts to keep an eye on:

Colorectal Cancer

LBA13: In the phase 2 GRANITE study (NCT05141721), experts are exploring individualized neoantigen-targeting immunotherapy in metastatic microsatellite-stable colorectal cancer (CRC) (MSS-CRC).² Early results show that GRANITE, a personalized neoantigen vaccine, improved progression-free survival (PFS) and long-term circulating tumor DNA (ctDNA) response compared with standard fluoropyrimidine and bevacizumab (Avastin).

Key phase 2 end points include molecular response (ctDNA decrease ≥ 30%), while phase 3 will focus on PFS. This study highlights the potential of personalized vaccines to transform MSS-CRC treatment.

LBA14: Findings from CALGB/Alliance SWOG 80702 (NCT01150045), a randomized, phase 3 trial, will be presented and are expected to further underscore the prognostic and predictive role of ctDNA in stage III colon cancer treated with celecoxib (Celebrex).³ The goal of the study is to compare how well oxaliplatin, leucovorin, and fluorouracil (FOLFOX) work together when given with or without celecoxib for the treatment of patients with stage III colon cancer previously treated with surgery.

Prior findings from the study have shown that the addition of celecoxib for 3 years to standard adjuvant chemotherapy did not significantly improve disease-free survival vs placebo.

LBA125: A phase 3 trial is investigating the role of low-dose aspirin in reducing recurrence rates among patients with CRC harboring PI3K pathway alterations. These 3-year results may clarify the role of aspirin as an adjunct therapy for specific patient subgroups.⁴

LBA143: The CheckMate 8HW (NCT04008030) trial is comparing nivolumab plus ipilimumab (Yervoy) with nivolumab monotherapy in MSI-H/dMMR metastatic CRC.⁵ At last year’s ASCO GI meeting, this combination given as a first-line treatment led to statistically significant and clinically meaningful improvements in PFS vs investigator’s choice of chemotherapy among patients with microsatellite instability–high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer, meeting a dual primary end point of the study.

“There was the first readout of the combination immunotherapy from the CheckMate 8HW study that was looking at nivolumab/ipilimumab, which is a combination immunotherapy, anti–CTLA-4 with anti–PD-1, vs chemotherapy. They also had an arm of immunotherapy that we do not have enough data on yet, but the hazard ratio in terms of the proportion of people who were cancer-free was striking at 72% vs 14% or so for chemotherapy. The hazard ratio was [around] 0.21, so almost a 79% reduction in the risk. It is a huge benefit, and you could see the plateauing of immunotherapy,” explained Pashtoon Kasi, MD, MS, medical director at City of Hope, in an interview with Targeted Oncology^TM.

“Immunotherapy in the MSI-high subset of patients continues to amaze us, and it is holding true with these combination therapies even more,” he continued.

With encouraging results, this combination may offer an enhanced approach for immunotherapy-sensitive CRC populations.

LBA248: KEYFORM-007 is a phase 3 study (NCT05064059) assessing the co-formulation of the anti–LAG-3 antibody favezelimab and pembrolizumab (Keytruda) in previously treated PD-L1–positive metastatic CRC. Previously reported data showed that this combination did not extend survival compared with standard care.⁶ However, the findings add to the understanding of checkpoint inhibitor efficacy in this setting.

The fixed-dose combination of favezelimab and pembrolizumab is also being investigated in the KEYFORM-008 study (NCT05508867) for the treatment of patients with PD–(L)1-refractory classical Hodgkin lymphoma.

Gastric cancer cells: © LASZLO - stock.adobe.com

Gastric and Gastroesophageal Cancer

LBA331: The EORTC-1203 GITC INNOVATION trial (NCT02205047) is evaluating the integration of trastuzumab (Herceptin), with or without pertuzumab (Perjeta), into perioperative chemotherapy for patients with HER2-positive stomach cancer.⁷ According to first results from the trial presented at the 2023 ASCO Annual Meeting, the primary end point analysis did not meet the pre-specified criteria of efficacy for this combination. However, perioperative chemotherapy with trastuzumab led to promising response rates, emphasizing the need for follow-up data.

“[INNOVATION] is a global, phase 2 trial in HER2-positive gastric cancer. This has 3 arms comparing perioperative chemotherapy, whatever standard of care it is in the country, plus trastuzumab or adding trastuzumab with pertuzumab. I think it failed to meet the end point of a 20% better path response rate, but there was a better path response rate,” explained Yanghee Woo, MD, surgical oncologist in the Division of Surgical Oncology, associate professor in the Department of Surgery, vice chair of international affairs, director of the Gastroenterology and Minimally Invasive Therapies Program at City of Hope, in a previous interview with Targeted Oncology.

Now, the overall survival (OS) results could cement the role of HER2-targeted therapies in perioperative settings.

Abstract 332: The ASPEN-06 phase 2/3 study (NCT05002127) of evorpacept (ALX148), a CD47 myeloid checkpoint inhibitor, is examining outcomes in HER2-overexpressing gastric or gastroesophageal junction (GEJ) cancer. According to topline findings from the study, clinically meaningful improvements in overall response rate (ORR) and duration of response were observed in patients with previously treated HER2-positive advanced gastric or GEJ cancer.⁸

Final analysis of the phase 2 portion may reveal whether targeting CD47 improves responses to HER2-directed therapies.

Abstract 398: Five-year follow-up data from CheckMate 649 (NCT02872116) will be presented at the meeting, looking to confirm the long-term benefits of nivolumab plus chemotherapy as first-line treatment for advanced gastric, GEJ, and esophageal adenocarcinomas.⁹

Nivolumab plus chemotherapy was approved by the FDA on April 16, 2021, for the first-line treatment of gastric/GEJ cancer without restriction by PD-L1 expression, based on findings from the CheckMate 649 study. Here, the combination led to statistically significant and clinically meaningful improvements in PFS and OS compared with chemotherapy and placebo. In patients with a combined positive score (CPS) of greater than 5, the PFS HR was 0.68 (95% CI, 0.56-0.81) and the OS HR was 0.71 (98.4% CI, 0.59-0.86). In patients with a CPS of 1 or greater, the OS HR was 0.77 (99.3% CI, 0.64-0.92). In all randomized patients, the OS HR was 0.80 (99.3% CI, 0.68-0.94).

“We saw unequivocal improvements in overall survival for the patients with PD-L1 CPS 5 or higher with a nearly 3-month improvement in OS and with an HR of 0.7, which was highly statistically significant [95% CI, 0.61-0.71]. We also saw a significant improvement in PFS of about 2 months [HR, 0.71; 95% CI, 0.61-0.82],” explained David H. Ilson, MD, PhD, during a Case-Based Roundtable® event.¹⁰ “It’s key to note the tail on the [Kaplan-Meier] curve here showing that patients get sustained benefit from this treatment sometimes beyond 2 years of therapy, which is unprecedented.”

Cancer detection and screening as a treatment for malignant cells with a biopsy or testing caused by carcinogens and genetics with a cancerous cell as an immunotherapy symbol: © freshidea - stock.adobe.com

Esophageal Cancer

LBA329: The phase 3 SCIENCE trial (NCT05244798) is evaluating chemotherapy plus sintilimab (Tyvyt) and chemoradiotherapy plus sintilimab vs chemoradiotherapy alone as neoadjuvant treatments for patients with resectable locally advanced esophageal squamous cell carcinoma (ESCC).¹ The multicenter, randomized study aims to determine if sintilimab can enhance treatment efficacy and provide a new standard for this patient population. Preliminary results will be presented at the meeting.

Pancreatic Cancer

Abstract 675: In the LAPIS trial (NCT03941093), experts are evaluating chemotherapy with or without pamrevlumab (FG-3019) for locally advanced pancreatic cancer (LAPC) treatment. Recent data suggest pamrevlumab failed to meet survival end points in advanced settings.¹¹

LAPIS is a phase 3 study comparing gemcitabine and nab-paclitaxel or oxaliplatin, folinic acid, irinotecan, and fluorouracil (FOLFIRINOX) with and without pamrevlumab. The median OS was 17.3 months in the pamrevlumab arm vs 17.9 months in the comparator arm (HR, 1.08; 95% CI, 0.83-1.41; stratified log-rank P =.55).

The LAPIS study results to be presented at the ASCO GI meeting could help provide clarity regarding these primary end point findings.

REFERENCES:

1. Sintilimab plus NCT or NCRT versus NCRT for ESCC. Clinical Drug Experience Knowledgebase. Updated October 25, 2022. Accessed January 21, 2025. https://cdek.pharmacy.purdue.edu/trial/NCT05244798/

2. A study of a patient-specific neoantigen vaccine in combination with immune checkpoint blockade for patients with metastatic colorectal cancer. ClinicalTrials.gov. Updated December 22, 2023. Accessed January 21, 2025. https://classic.clinicaltrials.gov/ct2/show/NCT05141721

3. Meyerhardt JA, Shi Q, Fuchs CS, et al. Effect of Celecoxib vs Placebo Added to Standard Adjuvant Therapy on Disease-Free Survival Among Patients With Stage III Colon Cancer: The CALGB/SWOG 80702 (Alliance) Randomized Clinical Trial. JAMA. 2021;325(13):1277-1286. doi:10.1001/jama.2021.2454

4. Adjuvant low dose aspirin in colorectal cancer (ALASCCA). ClinicalTrials.gov. Updated September 19, 2024. Accessed January 21, 2025. https://clinicaltrials.gov/study/NCT02647099

5. Andre T, Elez E, Van Cutsem E, et al. Nivolumab (NIVO) plus ipilimumab (IPI) vs chemotherapy (chemo) as first-line (1L) treatment for microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC): First results of the CheckMate 8HW study. Presented at the 2024 Gastrointestinal Cancers Symposium; San Francisco, CA, January 18-20, 2024. LBA 768.

6. Merck provides update on phase 3 KEYFORM-007 trial evaluating investigational fixed-dose combination of favezelimab and pembrolizumab for patients with previously treated PD-L1 positive microsatellite stable metastatic colorectal cancer. News release. Merck. September 25, 2024. Accessed January 21, 2025. https://tinyurl.com/7hw84z2c

7. Wagner AD, Grabsch HI, Mauer M, et al. Integration of trastuzumab (T), with or without pertuzumab (P), into perioperative chemotherapy (CT) of HER-2 positive gastric (GC) and esophagogastric junction cancer (EGJC): First results of the EORTC 1203 INNOVATION study, in collaboration with the Korean Cancer Study Group, and the Dutch Upper GI Cancer group. J Clin Oncol. 2023;41:4057. Published 2023 May 31. doi:10.1200/JCO.2023.41.16_suppl.405

8. ALX Oncology reports topline data from ASPEN-06 phase 2 trial demonstrating evorpacept improves tumor response in patients with HER2-positive gastric cancer. News release. ALX Oncology Holdings Inc. July 31, 2024. Accessed January 21, 2025. https://tinyurl.com/449hwceu

9. Janjigian YY, Ajani JA, Moehler M, et al. First-line nivolumab plus chemotherapy for advanced gastric, gastroesophageal junction, and esophageal adenocarcinoma: 3-year follow-up of the phase III CheckMate 649 trial. J Clin Oncol. 2024;42(17):2012-2020. doi:10.1200/JCO.23.01601

10. Shitara K, Moehler MH, Ajani JA, et al. Nivolumab (NIVO) + chemotherapy (chemo) vs chemo as first-line (1L) treatment for advanced gastric cancer/gastroesophageal junction cancer/esophageal adenocarcinoma (GC/GEJC/EAC): 4 year (yr) follow-up of CheckMate 649. J Clin Oncol. 2024;42(suppl 3):306. doi:10.1200/JCO.2024.42.3_suppl.306

11. FibroGen announces topline results from two late-stage pamrevlumab pancreatic cancer studies and provides corporate update. News release. FibroGen, Inc. July 30, 2024. Accessed January 21, 2025. https://tinyurl.com/ycxf456f