The first patient was dosed in a phase 1/2 trial of evofosfamide with checkpoint inhibitors for hypoxia-reversal in resistant solid tumors.
Trial Name: A Phase 1/2 Immunotherapy Study of Evofosfamide in Combination with Zalifrelimab and Balstilimab in Patients with Advanced Solid Malignancies
ClinicalTrials.gov Identifier: NCT06782555
Sponsor: ImmunoGenesis
Recruitment Contact: Charles Schweizer, PhD, 346-772-0336, charles.schweizer@immunogenesis.com
Completion Date: January 2028
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The first patient has been dosed in a phase 1/2 trial (NCT06782555) evaluating evofosfamide (IMGS-101), a hypoxia-reversal agent, in combination with balstilimab (AGEN2034) and zalifrelimab (AGEN1884) for the treatment of adult patients with locally advanced or metastatic castration-resistant prostate cancer (CRPC), pancreatic cancer, and human papillomavirus-(HPV) negative squamous cell carcinoma of the head and neck (SCCHN).1
"Launching this trial represents a significant milestone in our mission to target key mechanisms of immune resistance," said James Barlow, ImmunoGenesis president and chief executive officer, in a press release. "By targeting and reversing hypoxia, we aim to unlock the immune system's full potential and redefine the therapeutic landscape for these cancers with high unmet medical needs.”
Tumor hypoxia creates an immunosuppressive barrier that limits T-cell infiltration and suppresses immune responses. In cancers like CRPC, pancreatic, and SCCHN, hypoxia often contributes to poor responses to immune checkpoint inhibitors.
Evofosfamide, a 2-nitroimidazole hypoxia-activated prodrug, aims to reverse hypoxia and potentially restore T-cell access to tumors, enhancing the efficacy of checkpoint inhibitors.1 Preclinical and early phase 1 data suggest that evofosfamide can restore T-cell function and synergize with checkpoint inhibitors, offering a promising approach to overcoming immune resistance.
The open-label, multicenter trial being conducted at The University of Texas MD Anderson Cancer Center and other sites includes a dose-escalation phase to determine the optimal dose of evofosfamide, followed by a dose-expansion phase to assess safety, pharmacokinetics, and antitumor activity in combination with balstilimab and zalifrelimab.
Enrollment in the study is open to patients with histologically confirmed locally advanced or metastatic castration-resistant prostate cancer, pancreatic cancer, or HPV-negative SCCHN with a minimum estimated life expectancy of at least 3 months.2 Patients are required to have an ECOG performance status of 0 to 2, measurable disease as defined by RECIST 1.1, and adequate bone marrow and liver function.
The primary end point of the study is to assess the incidence and severity of adverse events including dose-limiting toxicities. Secondary end points include serious AEs, discontinuations, and deaths, progression-free survival, objective response rate, and duration of response per RECIST 1.1 and iRECIST, overall survival, pharmacokinetics, and the detection of anti-drug antibodies of zalifrelimab and balstilimab.
The estimated study completion date is January 2028.
"This trial marks an exciting step forward in addressing one of the key challenges in cancer immunotherapy," said Charles Schweizer, PhD, senior vice president of clinical development at ImmunoGenesis, in a press release. "Hypoxia limits T-cell infiltration and suppresses immune responses, especially in prostate, pancreatic, and head and neck cancers. By reversing hypoxia, [evofosfamide] may restore T-cell access to tumors, enhancing the effectiveness of checkpoint inhibitors and potentially transforming outcomes in these hard-to-treat cancers."
