A Phase I Study of Nimotuzumab With Nivolumab in Advanced Non-small Cell Lung Cancer and Head and Neck Squamous Cell...

Nimotuzumab is a monoclonal antibody (mAb) that targets the epidermal growth factor receptor. Nivolumab is an anti-programmed death 1 (anti-PD1) mAb that overcomes immune checkpoint inhibition. This trial aimed to evaluate the safety, tolerability, and efficacy of combination treatment as second-line therapy in non-small cell lung cancer (NSCLC) and head and neck squamous cell cancer (HNSCC).

This was a single-center, single-arm, non-randomized study utilizing a three plus three dose escalation design. Nimotuzumab was given intravenously (IV) at escalating doses of 200 mg, 300 mg, and 400 mg after nivolumab infusion at 240 mg IV every two weeks in a 28-day cycle. Recommended phase 2 dose (RP2D) and dose-limiting toxicities (DLT) were determined. Treatment was continued until disease progression, unacceptable toxicity, or withdrawal from the trial. Serial EKG and troponin checks were performed.

Seven patients were enrolled across the 200 mg and 300 mg nimotuzumab dose levels. The median age was 64.1 years. Four patients (57.1%) were males. Five (71.4%) had NSCLC, and the predominant histology was pure adenocarcinoma (n = 4, 57.1%). Four patients (57.1%) had Kirsten rat sarcoma (KRAS) mutation. All patients had disease progression after platinum-based and anti-PD1 therapy prior to enrollment, except for two NSCLC patients who were enrolled to receive this treatment after initial platinum-based chemotherapy only. Four patients (two from each dose level) had troponin elevation (median = 0.1 ng/ml, range = 0.07 to 0.3 ng/ml) lasting at least 24 hours, which normalized next week without any associated chest pain, except for one patient (HNSCC) with potential treatment-related DLT. Disease control rate was 42.9% (stable disease as best response, n = 3).

Asymptomatic troponin elevation was seen with this combination treatment. While there were no clinically significant adverse cardiac outcomes, further development was terminated due to the competitive landscape.