iTeos Therapeutics has announced its decision to deprioritize inupadenant, an adenosine A2A antagonist, for the treatment of non-small cell lung cancer (NSCLC) following the presentation of mid-stage data at the ESMO Immuno-Oncology Congress. The company will shift its focus towards other programs, notably its TIGIT therapies, including belrestotug (EOS-448). This strategic shift comes after evaluating the results from the Phase II A2A-005 trial, which assessed the efficacy of inupadenant in combination with platinum-doublet chemotherapy in patients with metastatic NSCLC who had previously undergone immunotherapy. The decision reflects a reassessment of the clinical benefit and future investment strategy for inupadenant within iTeos's oncology pipeline.
Phase II A2A-005 Trial Results
The Phase II A2A-005 trial evaluated inupadenant at doses of 40mg, 60mg, or 80mg twice daily in combination with pemetrexed and carboplatin. The topline data, which included 36 patients eligible for safety and efficacy evaluation, indicated that the combination therapy met its primary safety and tolerability endpoints, with no dose-dependent toxicities observed. However, the secondary endpoints, while technically met, did not demonstrate a significant advantage over existing treatments. The objective response rate (ORR) across all patients was 63.9% (53.3% at 40mg, 66.7% at 60mg, and 73.3% at 80mg).
Comparative Efficacy and Strategic Shift
The observed ORR with inupadenant in combination with chemotherapy was comparable to that achieved with standard-of-care platinum-based doublet therapy alone, which has shown an average ORR of 66.7% in similar patient populations post-immunotherapy. This suggests that the addition of inupadenant may not provide a substantial clinical benefit over existing, less expensive treatments. Consequently, iTeos has decided to reallocate resources to its TIGIT program, which has demonstrated more promising results in early-stage trials.
Focus on TIGIT Antibody Belrestotug
iTeos's pipeline now emphasizes clinical-stage programs targeting validated immunosuppressive pathways, particularly the Phase III trial of its TIGIT antibody belrestotug (EOS-448), being developed and marketed in collaboration with GSK. Phase II TIGIT trial results, shared in September, indicated a confirmed overall response rate difference of over 30% between the investigational treatment and monotherapy, heightening anticipation for the Phase III trial outcomes. This strategic pivot underscores iTeos's commitment to developing differentiated therapies with the potential to offer significant clinical advantages in the treatment of NSCLC and other cancers.
Leadership Perspective
Michel Detheux, president and CEO of iTeos, stated, "While the initial signal for inupadenant’s RP2D in the A2A-005 trial compared to chemotherapy alone is encouraging and supports its differentiated, insurmountable profile, we as well as our scientific and clinical advisory boards believe it does not meet sufficient level of clinical activity to warrant further investment. We remain committed to focusing our resources on developing differentiated, first- or best-in-class therapies and look forward to providing updates on our pipeline in 2025."
