KEY TAKEAWAYS
- A phase I/II trial assessed avelumab’s safety in combination with utomilumab, ivuxolimab, or radiation for patients with advanced malignancies.
- The primary endpoints were safety, tolerability, and dose-limiting toxicities, and secondary objectives were evaluating response rate, progression-free survival, and overall survival.
- Combining immune checkpoint inhibitors with agonists showed modest activity, indicating potential for future research in GI malignancies.
Combining OX40 and 4–1BB checkpoint agonists boosts T cell activity but also elevates PD-L1 on cancer cells. Preclinical studies suggested that avelumab, utomilumab, and ivuxolimab together may enhance T cell function and counteract PD-L1 effects for clinical benefits.
Radiation therapy’s tissue abscopal effect can improve antigen presentation and supplement PD-L1 blockade. Thus, researchers conducted a single institution, open-label, multi-arm, non-randomized, phase 1/2 clinical trial of avelumab in combination with utomilumab, ivuxolimab, or radiation therapy in advanced cancer patients.
Researchers presented a subgroup analysis focused on GI tumors (pancreatic, colon, gastric, and hepatocellular cancers). The study arms included combinations of avelumab with ivuxolimab (Arm B), avelumab with utomilumab and ivuxolimab (Arm C), avelumab and ivuxolimab with radiation therapy (Arm E), and avelumab, utomilumab, and ivuxolimab with radiation therapy (Arm F).
Primary goals were safety, tolerability, and dosing; secondary objectives involved efficacy measures like response rate, progression-free survival, and overall survival.
The study included 31 patients diagnosed with pancreatic (21), colorectal (8), HCC (1), and gastric (1) cancers. Common treatment-related adverse events comprised chills (12.9%), diarrhea (9.7%), colitis (9.7%), fatigue (6.5%), and fever (6.5%). Notably, there were three instances of grade 3 diarrhea and colitis (9.7%) observed each, with no other severe adverse events based on CTCAE v4.03.
Among 24 patients evaluated for response, 9 (37.5%) had immune-related stable disease (irSD), 14 (58.3%) had immune-related progressive disease (irPD), and one had clinical disease progression. Median progression-free survival (mPFS) stood at 2 months, and median overall survival (mOS) at 5.6 months. Correlative studies are ongoing.
The combination of immune checkpoint inhibitors and agonists shows moderate effectiveness without notable safety issues in patients with advanced gastrointestinal cancers. These study results offer valuable insights for future research in this area.
Source: https://jitc.bmj.com/content/11/Suppl_1/A664
Clinical Trial: https://clinicaltrials.gov/study/NCT03217747
Ahmed J, Knisely A, Stephen B, et al584 Phase I/II study to evaluate the safety and tolerability of avelumab in combination with other anti-cancer therapies in patients with advanced malignanciesJournal for ImmunoTherapy of Cancer 2023;11:doi: 10.1136/jitc-2023-SITC2023.0584.
