134P - Intracranial (IC) progression-free survival (PFS) with ivonescimab (Ivo) compared to placebo in the HARMONi-A trial of patients (Pts) with previously treated EGFR mutation-positive (EGFRm+) non-small cell lung cancer (NSCLC)

Background

Ivonescimab (ivo, AK112/SMT112) is a bispecific antibody against PD-1 and VEGF that demonstrates cooperative binding. The HARMONi-A trial aimed to evaluate the efficacy and safety of ivo combined with chemo versus chemo and placebo in pts with EGFRm+ NSCLC previously treated with EGFR tyrosine kinase inhibitor (TKI) therapy. The current analysis evaluated the IC PFS of patients who received ivo vs. placebo with chemo on the two arms of HARMONi-A.

Methods

Pts were randomized 1:1 with stratification by exposure to third-generation EGFR-TKI (yes/no) and presence of brain metastases (BMs) at baseline (yes/no) to receive ivo (20 mg/kg) plus pemetrexed (500 mg/m2)/carboplatin (AUC 5) or placebo with same chemo every 3 weeks x 4 cycles followed by maintenance therapy of ivo or placebo with pemetrexed. Overall PFS by independent radiologic review committee (IRRC) was the primary endpoint. Brain scans were performed in all pts at baseline and progression and, for pts with baseline BMs, at scheduled assessments until progression. IC PFS was defined as time from random assignment until date of objective IC progression or death from any cause in the absence of known IC progression.

Results

A total of 322 pts were randomized (161 to each arm); 21.7% vs 23.0% of pts had baseline BMs in the ivo and placebo arms, respectively. As of March 10, 2023, median (med) follow up time was 7.9 months (mo). Pts assigned to ivo with chemo demonstrated a significantly superior PFS by IRRC compared to placebo with chemo (med 7.1 vs 4.8 mo; HR 0.46 [0.34, 0.62], P < 0.0001); overall PFS was improved in pts without BMs (HR 0.48 [0.34-0.69]) and those with baseline BMs (HR 0.40 [0.22-0.73]). IC PFS with ivo/chemo was significantly improved compared to placebo/chemo in the intent-to-treat population (med not reached in either arm; HR 0.39 [0.24, 0.64], p < 0.001) and in pts with BMs at baseline (med 8.4 vs 5.4 mo; HR 0.33 [0.15, 0,74], p = 0.005).

Conclusions

In addition to improving previously reported efficacy endpoints on HARMONi-A, ivo added to chemo significantly improved IC PFS among pts with advanced EGFRm+ NSCLC whose disease had progressed on prior EGFR TKI therapy.

Clinical trial identification

NCT05184712.

Legal entity responsible for the study

Akeso Biopharma.

Funding

Akeso Biopharma.

Disclosure

L. Zhang: Financial Interests, Institutional, Research Grant, Research support: Hengrui, BeiGene, Xiansheng, Eli Lilly, Novartis, Roche, Hansoh, Bristol Myers Squibb Pharma; Financial Interests, Institutional, Speaker, Consultant, Advisor: Beigene, Xiansheng Pharma, MSD. H.(West: Financial Interests, Institutional, Full or part-time Employment: Summit Therapeutics; Non-Financial Interests, Institutional, Member of Board of Directors, Founder, previously President & CEO, currently a member of the Board of Directors: Global Resource for Advancing Cancer Education (GRACE). W. Li: Financial Interests, Personal, Full or part-time Employment: Akeso Biopharma. Y. Xia: Financial Interests, Institutional, Full or part-time Employment: Akeso Biopharma; Financial Interests, Institutional, Member of Board of Directors: Akeso Biopharma. All other authors have declared no conflicts of interest.