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A Study of Evofosfamide in Combination with Zalifrelimab and Balstilimab | Clinical Trials | Clareo Health

RECRUITINGPHASE1/PHASE2

A Study of Evofosfamide in Combination with Zalifrelimab and Balstilimab

A Phase 1/2 Immunotherapy Study of Evofosfamide in Combination with Zalifrelimab and Balstilimab in Patients with Advanced Solid Malignancies

NCT06782555•ImmunoGenesis

View on ClinicalTrials.gov

Summary

The purpose of this Phase 1/2 study is to test the overall safety, tolerability, and effectiveness of the combination investigational drugs evofosfamide, zalifrelimab, and balstilimab in treating advanced or metastatic castration-resistant prostate cancer, pancreatic cancer, and human papilloma virus (HPV)-negative squamous cell carcinoma of the head and neck (SCCHN).

Detailed Description

Tumor hypoxia can lead to poor effector T-cell penetration and immunosuppressive signaling via myeloid-derived suppressor cells, myofibroblasts, and regulatory T-cells. Disruption of these hypoxic regions within the tumor microenvironment by the hypoxia-directed cytotoxic agent evofosfamide may enhance the ability of immune checkpoint inhibitors to reject otherwise resistant solid tumors. The hypothesis tested in this study is that evofosfamide, by specifically targeting the hypoxic tumor microenvironment, may enhance the anti-tumor effects of the immune checkpoint inhibitors zalifrelimab (anti-CTLA-4) and balstilimab (anti-PD-1) in select tumors that are generally resistant to therapy. In the Phase 1 dose escalation part of the study, the maximum tolerated dose (or maximum allowable dose) of evofosfamide in combination with zalifrelimab and balstilimab will be determined. A recommended Phase 2 dose (RP2D) will be determined based on safety and the totality of data. The Phase 2 dose expansion part of the study will evaluate the Phase 2 dose of the triplet combination in 3 cohorts: 1) patients with locally advanced or metastatic castration-resistant prostate cancer; 2) patients with locally advanced or metastatic pancreatic cancer; and 3) patients with locally advanced or metastatic HPV-negative SCCHN. Each cohort expansion will be carried out independently.

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•1. Histologically confirmed locally advanced or metastatic castration-resistant prostate cancer, pancreatic cancer, or HPV-negative SCCHN for which no other lines of standard therapy with demonstrated clinical benefit are available or appropriate as treatment.
•2. Appropriate to enter a clinical trial with a minimum estimated life expectancy of at least 3 months.
•3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
•4. Measurable disease as defined by RECIST 1.1. Patients with castration-resistant prostate cancer can have measurable or evaluable disease per PCWG3 criteria. Patients with evaluable disease must have documented evidence of PD as defined by any of the following:
•* PSA progression: minimum of 2 rising values (3 measurements) obtained a minimum of 7 days apart with the last result being at least ≥4.0 ng/mL.
•* New or increasing non-bone disease per RECIST 1.1 criteria.
•* Positive bone scan with 2 or more new lesions (PCWG3).
•5. Adequate bone marrow function as defined by the following laboratory test results obtained within 7 days of Cycle 1 Day 1:
•* White blood cell count ≥2500 cells/mm3.
•* Absolute neutrophil count ≥1500 cells/mm3.
+12 more criteria

Exclusion Criteria

•1. A history of currently active/uncontrolled autoimmune diseases or disorders, including inflammatory bowel disease (including Crohn's disease and ulcerative colitis), rheumatoid arthritis, systemic sclerosis (scleroderma), systemic lupus erythematosus, or autoimmune vasculitis (eg, Wegener's granulomatosis).
•2. Patients with prior history of any Grade 3 or Grade 4 AEs from anti-CTLA-4, anti-PD-1/PD-L1, or anti-CTLA-4 and anti-PD-1/PD-L-1 combination therapy.
•3. History of acute diverticulitis, intra-abdominal abscess, gastrointestinal obstruction, abdominal carcinomatosis, or other known risk factors for bowel perforation.
•4. Patients on long-term systemic steroids (\>10 mg daily prednisone equivalent initiated \>2 weeks prior to study enrollment). Inhaled or topical steroids are permitted in the absence of active autoimmune disease.
•5. Any underlying medical or psychiatric condition, which in the opinion of the investigator, will make the administration of study treatment hazardous or obscure the interpretation of AEs, e.g., a condition associated with frequent diarrhea or chronic skin conditions, recent surgery (within 30 days) or colonic biopsy from which the patient has not recovered, partial endocrine organ deficiencies, or substance abuse.
•6. Concomitant use of QT-prolonging drugs with a risk of causing Torsades de Pointes (TdP).
•7. History of risk factors for TdP, including family history of long QT syndrome.
•8. Corrected QT (QTc) interval of ≥470 msec calculated according to Fridericia's formula (QTc=QT/RR \[0.33\]).
•9. Sustained systolic blood pressure (BP) \>140 mmHg or \<90 mmHg and sustained diastolic BP \>100 mmHg or \<60 mmHg.
•15. Active or chronic hepatitis B or C virus infection. Patients with a history of HCV infection must have completed curative antiviral treatment and must have a viral load below the limit of quantification. A patient who is HCV Ab positive but HCV RNA negative due to prior treatment or natural resolution is eligible.
+5 more criteria

Locations (1)

MD Anderson Cancer Center

Houston, Texas, United States

Key Dates

Start Date

January 8, 2025

Primary Completion Date

October 1, 2027

Completion Date

January 1, 2028

Last Updated

January 21, 2025

Enrollment

ESTIMATED participants

Conditions

Metastatic Prostate CancerMetastatic Head and Neck Squamous Cell CarcinomaMetastatic Pancreatic Cancer

Interventions

Evofosfamide

DRUG

Zalifrelimab

DRUG

Balstilimab

DRUG

Contacts

Charles Schweizer, PhD

CONTACT

346-772-0336 charles.schweizer@immunogenesis.com

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Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: January 21, 2025Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

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A Study of Evofosfamide in Combination with Zalifrelimab and Balstilimab

Inclusion Criteria

Exclusion Criteria

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