Cancer of the lung | Image Credit: © Crystal light - www.stock.adobe.com
Ivonescimab (AK112) has been dosed for the first time in the phase 3 HARMONi/AK112-301 study of ivonescimab vs the combination of tislelizumab (BGB-A317) plus chemotherapy as first-line therapy for patients with locally advanced or metastatic non-squamous non–small cell lung cancer (NS-NSCLC).1
Ivonescimab is a first-in-class investigational PD-1/VEGF bispecific antibody. The drug is being investigated in multiple clinical trials occurring worldwide.
In the randomized, double-blind, multicenter, phase 3 study (NCT05184712), 470 patients with locally advanced or metastatic NS-NSCLC will be assigned 1:1 to receive either ivonescimab in combination with pemetrexed and carboplatin or placebo in combination with pemetrexed and carboplatin. The ivonescimab combination in the experimental arm will be administered every 3 weeks (Q3W) for up to 4 cycles followed by maintenance therapy on day 1 of each cycle, Q3W for up to 2 years. Administration of placebo and chemotherapy in the control arm will match the doses and dose scheduled of the experimental arm.2
About the Phase 3 HARMONi Study
Trial Name: A Randomized, Double-blind, Multi-center, Phase III Study of AK112 or Placebo Combined With Pemetrexed and Carboplatin in Patients With EGFR-mutant Locally Advanced or Metastatic Non-squamous NSCLC Who Have Failed to EGFR-TKI Treatment
ClinicalTrials.gov Identifier: NCT05184712
Sponsor: Summit Therapeutics
Recruitment Contact: Lori Styles, MD, 1-833-256-0522, email@example.com
Completion Date: January 1, 2026
HARMONi aims to evaluate the efficacy and safety of ivonescimab plus chemotherapy using the coprimary end points of progression-free survival (PFS) by independent review committee (IRC) assessment per RECIST v1.1, in the intent-to-treat (ITT) population and overall survival in the ITT population. As secondary end points, the study is investigating objective response rate, disease control rate, duration of response, time to response, PFS by investigator assessment, the incidence and severity adverse events (AEs) and serious AEs, observed concentrations of AK112, and the percentage of patients with detectable anti-drug antibodies.
Patients eligible to undergo treatment in the HARMONi study are 18 years of age or older with an ECOG performance score of 0 or 1 and a life expectancy of at least 3 months. All patients are required to have locally advanced or metastatic NS disease, major organ function prior to treatment, and a confirmed EGFR activating mutation, and at least 1 measurable non-brain tumor lesion per RECIST v1.1. In terms of prior therapy, patients must have received a third-generation EGFR tyrosine kinase inhibitor (TKI) to enroll in the study.
Those ineligible for the study are patients with small cell carcinoma components, other driver gene mutations, other active malignancies within the past 3 years, and other comorbidities that may interfere with the efficacy and safety of study treatment. Patients who were previously treated with an EGFR TKI, palliative local treatment, nonspecific immunomodulatory treatment within 2 weeks prior to the first dose of study treatment are ineligible to enroll. The study also excludes those who have received chest radiation therapy prior to the first dose.
1. Akeso announced first patient dosed in Phase 3 trial of ivonescimab versus tislelizumab for first-line treatment of squamous NSCLC. News release. Akeso, Inc. August 18, 2023. Accessed August 23, 2023. https://www.akesobio.com/en/media/akeso-news/230818/
2. Phase 3 clinical study of AK112 for NSCLC patients. ClinicalTrials.gov. Updated May 25, 2023. Accessed August 23, 2023. https://clinicaltrials.gov/study/NCT05184712?term=NCT05184712&rank=1