Augmenting antibody response to EGF-depleting immunotherapy: Findings from a phase I trial of CIMAvax-EGF in combination with nivolumab in advanced stage NSCLC

Rachel Evans; Kelvin Lee; Paul K Wallace; Mary Reid; Jason Muhitch; Askia Dozier; Circe Mesa; Patricia L Luaces; Orestes Santos-Morales; Adrienne Groman; Carlos Cedeno; Aileen Cinquino; Daniel T Fisher; Igor Puzanov; Mateusz Opyrchal; Christos Fountzilas; Tong Dai; Marc Ernstoff; Kristopher Attwood; Alan Hutson; Candace Johnson; Zaima Mazorra; Danay Saavedra; Kalet Leon; Agustin Lage; Tania Crombet; Grace K Dy

doi:10.3389/fonc.2022.958043

Augmenting antibody response to EGF-depleting immunotherapy: Findings from a phase I trial of CIMAvax-EGF in combination with nivolumab in advanced stage NSCLC

Front Oncol. 2022 Aug 3:12:958043. doi: 10.3389/fonc.2022.958043. eCollection 2022.

Authors

Rachel Evans¹, Kelvin Lee², Paul K Wallace¹, Mary Reid¹, Jason Muhitch¹, Askia Dozier¹, Circe Mesa³, Patricia L Luaces³, Orestes Santos-Morales³, Adrienne Groman¹, Carlos Cedeno¹, Aileen Cinquino¹, Daniel T Fisher¹, Igor Puzanov¹, Mateusz Opyrchal², Christos Fountzilas¹, Tong Dai¹, Marc Ernstoff⁴, Kristopher Attwood¹, Alan Hutson¹, Candace Johnson¹, Zaima Mazorra³, Danay Saavedra³, Kalet Leon³, Agustin Lage³, Tania Crombet³, Grace K Dy¹

Affiliations

¹ Roswell Park Comprehensive Cancer Center, Buffalo, NY, United States.
² Department of Medicine Indiana University Melvin and Bren Simon Comprehensive Cancer Center, Indianapolis, IN, United States.
³ Centro de Immunologia Molecular, La Habana, Cuba.
⁴ National Cancer Institute (NCI) Division of Cancer Treatment and Diagnosis, Bethesda, MD, United States.

Abstract

Background: CIMAvax-EGF is an epidermal growth factor (EGF)-depleting immunotherapy which has shown survival benefit as a switch maintenance treatment after platinum-based chemotherapy in advanced non-small cell lung cancer (NSCLC). The primary objective of this trial is to establish the safety and recommended phase II dose (RP2D) of CIMAvax-EGF in combination with nivolumab as second-line therapy for NSCLC.

Methods: Patients with immune checkpoint inhibitor-naive metastatic NSCLC were enrolled using a "3+3" dose-escalation design. Toxicities were graded according to CTCAE V4.03. Thirteen patients (one unevaluable), the majority with PD-L1 0%, were enrolled into two dose levels of CIMAvax-EGF.

Findings: The combination was determined to be safe and tolerable. The recommended phase 2 dose of CIMAvax-EGF was 2.4 mg. Humoral response to CIMAvax-EGF was achieved earlier and in a greater number of patients with the combination compared to historical control. Four out of 12 evaluable patients had an objective response.

Keywords: immune checkpoint inhibitor; immunotherapy; lung cancer; non-small cell lung cancer; vaccine.

Copyright © 2022 Evans, Lee, Wallace, Reid, Muhitch, Dozier, Mesa, Luaces, Santos-Morales, Groman, Cedeno, Cinquino, Fisher, Puzanov, Opyrchal, Fountzilas, Dai, Ernstoff, Attwood, Hutson, Johnson, Mazorra, Saavedra, Leon, Lage, Crombet and Dy.