iTeos Therapeutics presented interim clinical, translational, and preclinical data from its inupadenant program at the European Society for Medical Oncology Immuno-Oncology (ESMO IO) Congress 2024. The data included results from the Phase 2 A2A-005 trial, which evaluated inupadenant in combination with platinum-doublet chemotherapy in patients with post-immunotherapy metastatic non-small cell lung cancer (NSCLC).
The A2A-005 trial's dose escalation portion included 36 patients eligible for safety and efficacy evaluation. Patients received inupadenant at 40mg, 60mg, or 80mg twice daily (BID) in combination with carboplatin/pemetrexed. All patients had a minimum follow-up of 6 months, with baseline characteristics balanced across arms, though there was a slight imbalance of more patients with brain metastases in the 40mg and 80mg cohorts and ECOG status 0 favoring the 80mg cohort.
Clinical Trial Results
The primary endpoint of the safety of inupadenant in combination with carboplatin/pemetrexed was observed to be manageable and tolerable, with no dose-dependent toxicities. The overall response rate (ORR) was 63.9% across all patients (53.3% at 40mg, 66.7% at 60mg, and 73.3% at 80mg). The median progression-free survival (mPFS) was 7.7 months across all patients (5.6 months at 40mg and 6.6 months at 60mg; mPFS remains unreached at 80mg).
Specifically, the recommended Phase 2 dose (RP2D) of inupadenant 80mg + carboplatin/pemetrexed demonstrated a 73.3% ORR, with 64.6% of patients achieving landmark 6-month PFS.
Biomarker Analysis
Exploratory biomarker analysis showed that CXCL13, a B-cell chemokine and lymphoid structure marker associated with clinical activity, was restored by inupadenant after depletion by chemotherapy. This restoration occurred more quickly in patients with PFS greater than 6 months.
Company Decision
Despite these encouraging results, iTeos Therapeutics has decided to deprioritize the inupadenant program. According to Michel Detheux, Ph.D., president and chief executive officer of iTeos, while the initial signal for inupadenant's RP2D in the A2A-005 trial compared to chemotherapy alone is encouraging, the company and its scientific and clinical advisory boards believe it does not meet a sufficient level of clinical activity to warrant further investment. The company will focus its resources on developing differentiated, first- or best-in-class therapies and plans to provide updates on its pipeline in 2025.
Additional Data
Additional data presented at the ESMO IO Congress included findings that inupadenant promotes humoral responses in patients and preclinical models. A novel tumor adenosine signature was also presented as a potential tool for guiding indication selection for adenosine pathway inhibitors.
