A Study of Evofosfamide in Combination with Zalifrelimab and Balstilimab

NCT06782555 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: EVO-011
• Study Type: interventional
• Target: 71
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

Metastatic Prostate Cancer; Metastatic Head and Neck Squamous Cell Carcinoma; Metastatic Pancreatic Cancer

Outcome Measures

Primary Outcomes (1)

• Incidence and severity of adverse events including dose-limiting toxicities

  12 months

Secondary Outcomes (9)

• Serious adverse events, discontinuations, and deaths

  12 months

• Progression-free survival per RECIST 1.1 and iRECIST

  12 months

• Objective response rate per RECIST 1.1 and iRECIST criteria (or PCWG3/RECIST for prostate cancer)

  12 months

• Duration of response per RECIST 1.1 and iRECIST

  12 months

• Overall survival

  12 months

Study Arms (3)

Castration-resistant prostate cancer

EXPERIMENTAL

Evofosfamide + zalifrelimab + balstilimab

Drug: Evofosfamide; Drug: Zalifrelimab; Drug: Balstilimab

Pancreatic cancer

EXPERIMENTAL

Evofosfamide + zalifrelimab + balstilimab

Drug: Evofosfamide; Drug: Zalifrelimab; Drug: Balstilimab

Human papilloma virus-negative squamous cell carcinoma of the head and neck

EXPERIMENTAL

Evofosfamide + zalifrelimab + balstilimab

Drug: Evofosfamide; Drug: Zalifrelimab; Drug: Balstilimab

Interventions

Evofosfamide DRUG

Evofosfamide administered on Days 1 and 8 of Cycles 1, 2, and 3.

Castration-resistant prostate cancer; Human papilloma virus-negative squamous cell carcinoma of the head and neck; Pancreatic cancer

Zalifrelimab DRUG

Zalifrelimab administered on Day 8 of Cycles 1, 3, and 5.

Castration-resistant prostate cancer; Human papilloma virus-negative squamous cell carcinoma of the head and neck; Pancreatic cancer

Balstilimab DRUG

Balstilimab administered every 2 weeks beginning on Day 8 of Cycle 1.

Castration-resistant prostate cancer; Human papilloma virus-negative squamous cell carcinoma of the head and neck; Pancreatic cancer

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Appropriate to enter a clinical trial with a minimum estimated life expectancy of at least 3 months.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
• 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).
• 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.
• Absolute lymphocyte count \>500 cells/mm3.
• Hemoglobin ≥9 g/dL.
• Platelets ≥75,000 cells/mm3.
• Adequate liver function as defined by the following laboratory test results obtained within 7 days of Cycle 1 Day 1:
• Bilirubin ≤1.5 × institutional ULN; for patients with known Gilbert's syndrome, ≤3 × institutional ULN.

You may not qualify if:

• 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).
• 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.
• History of acute diverticulitis, intra-abdominal abscess, gastrointestinal obstruction, abdominal carcinomatosis, or other known risk factors for bowel perforation.
• 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.
• 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.
• Concomitant use of QT-prolonging drugs with a risk of causing Torsades de Pointes (TdP).
• History of risk factors for TdP, including family history of long QT syndrome.
• Corrected QT (QTc) interval of ≥470 msec calculated according to Fridericia's formula (QTc=QT/RR \[0.33\]).
• Sustained systolic blood pressure (BP) \>140 mmHg or \<90 mmHg and sustained diastolic BP \>100 mmHg or \<60 mmHg.
• Patients with newly diagnosed, uncontrolled and/or untreated cancer-related central nervous system disease. Patients with treated brain metastases that are radiographically or clinically stable for at least 2 weeks after therapy and have no evidence of cavitation or hemorrhage in the brain lesion(s) are eligible if they are asymptomatic and do not require corticosteroids (must have discontinued steroids at least 1 week prior to study enrollment).
• Uncontrolled intercurrent illness including, but not limited to, myocardial infarction within 6 months, unstable symptomatic ischemic heart disease, significant cardiac arrythmias, active uncontrolled infection requiring systemic therapy, or psychiatric illness/social situations that would limit compliance with study requirements.
• Major surgical procedure, open biopsy, or significant traumatic injury within 4 weeks prior to study enrollment.
• Current evidence of active and uncontrolled infection, New York Heart Association Class III-IV chronic heart failure, documented Child's class B and C cirrhosis, active symptomatic pancreatitis, or uncontrolled medical disease which, in the opinion of the investigator, could compromise assessment of study treatment efficacy.
• Active human immunodeficiency virus infection (Exception: patients with well-controlled HIV \[e.g., CD4 ≥ 350 cells/uL and undetectable viral load\] who have been on an effective (drug, dosage, and schedule associated with reduction and control of the viral load) antiretroviral therapy (ART) for ≥ 4 weeks are eligible). Patients with a history of acquired immunodeficiency syndrome (AIDS)-defining opportunistic infections in the last 12 months are not eligible. Note: Drug-drug interactions with ART occur via many mechanisms, with cytochrome P450 CYP3A4-mediated interactions being the most common. Patients who are using concurrent strong or moderate CYP3A4 inhibitors (e.g., ritonavir, cobicistat) or strong or moderate CYP3A4 inducers must be switched to an alternate effective ART regimen ≥ 4 weeks before study enrollment or should be excluded from the study if their regimen cannot be altered.
• 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.

Sponsors & Collaborators

• ImmunoGenesis: lead
• Agenus Inc.: collaborator

Study Sites (1)

MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

MeSH Terms

Conditions

Prostatic Neoplasms; Squamous Cell Carcinoma of Head and Neck; Pancreatic Neoplasms

Interventions

TH 302; balstilimab

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Head and Neck Neoplasms; Digestive System Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Central Study Contacts

Charles Schweizer, PhD

CONTACT

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 9, 2025
• First Posted: January 20, 2025
• Study Start: January 8, 2025
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): January 1, 2028
• Last Updated: January 21, 2025

Record last verified: 2025-01

Locations

US (1)