Phase 1b Study to Evaluate ATP128, VSV-GP128 and BI 754091, in Patients With Stage IV Colorectal Cancer

Running, not enrolling · Phase 1

Conditions studied: Colorectal Cancer, MSS, Stage IV Colon Cancer, Stage IV Rectal Cancer, Metastatic Colorectal Cancer, Liver Metastasis Colon Cancer

In brief

This is a multi-center, non-randomised Phase 1b study to evaluate the safety and tolerability of ATP128 alone or in combination with BI 754091 and of heterologous prime-boost ATP128 + VSV-GP128 in combination with BI 754091. ATP128 is a self-adjuvanted chimeric recombinant protein vaccine being developed in combination with programmed cell death 1 (PD-1) blockade for the treatment of microsatellite stable (MSS) patients not responding to PD-1 blockade. The PD-1 inhibitor being tested with ATP128 is the BI 754091 (Ezabenlimab) compound which belongs to the human immunoglobulin G4 (IgG4) subclass of antibodies. VSV-GP is a recombinant chimeric vesicular stomatitis virus (VSV, Indiana strain Rhabdoviridae) which carries the envelope glycoprotein (GP) of the visceral non neurotropic WE-HPI strain of the Lymphocytic choriomeningitis virus (LCMV, Arenaviridae) instead of the native VSV glycoprotein (G) and is developed as integral part of the prime-boost regimen together with ATP128. The Sponsor plans to enrol 96 patients with histologically or cytologically confirmed stage IV colorectal cancer coming form three different patient populations: * Cohort 1a: 6 patients with stage IV colorectal cancer (CRC) having failed standard of care (SoC) therapies * Cohorts 1b, 2a, 2c: 30 patients with stage IV microsatellite stable/mismatch repair-proficient (MSS/MMRp) CRC being in stable disease (SD) or partial response (PR) after first line of SoC (4-6 months duration at minimum) * Cohorts 2b, 4b: 30 patients with stage IV MSS/MMRp liver-limited disease Patients eligible for this study will be enrolled in one of the 8 cohorts depending on their disease: * Patients in Cohort 1a will receive ATP128 as single agent * Patients in Cohorts 1b, 2a, 2b, 2c will receive ATP128 in combination with BI 754091 * Patients in Cohorts 3, 4a, 4b will receive ATP128 and VSV-GP128 in combination with BI 754091

Key facts

Study ID: NCT04046445
Run by: Amal Therapeutics
People needed: 96
Starts: 2019-07-22
Expected to finish: 2025-08-31
Last updated by the study team: 2025-01-29

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

Cohort 1a
Ability to comprehend and willingness to provide written informed consent (ICF) for the study.
Age ≥ 18 years.
Patient with histologically or cytologically confirmed stage IV CRC who has failed standard therapies.
Must have received Standard of Care systemic treatment consisting of fluoropyrimidin- oxaliplatin and/or irinotecan based therapy for stage IV CRC disease.
Presence of at least 1 measurable lesion by computed tomography or magnetic resonance imaging per RECIST v1.1 as determined by the local site investigator/radiologist assessment.
Presence of at least one liver lesion amenable to repeated biopsy, ideally not the one being used for measuring.
Willingness to undergo two fresh liver biopsies (pre-treatment and on-treatment).
Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.
Life expectancy of at least 3 months.
Resolution of all toxicities and any toxic effect(s) of the most recent prior therapy to Grade 1 or less (except alopecia). Patients with ≤ Grade 2 neuropathy and Grade ≤ 2 fatigue are an exception and may enroll.
Adequate renal, hepatic, and hematologic functions as defined by laboratory parameters ≤ 7 days before study treatment initiation.
Absolute neutrophil count (ANC) ≥ 1.5 × 109/L.
Absolute lymphocyte count ≥ 0.5 × 109/L.
Platelets ≥ 100 × 109/L.
Hemoglobin level ≥ 9 g/dL.
Measured or calculated creatinine clearance (glomerular filtration rate can also be used in place of creatinine clearance) ≥ 50 mL/min according to the formula of Cockcroft-Gault.
Total bilirubin ≤ 1.5 × upper limit of normal (ULN); if total bilirubin is > 1.5 x ULN then direct bilirubin must be ≤ 1.5 × ULN. Patients with known Gilbert's Syndrome may enroll if total bilirubin ≤ 3 × ULN.
Alanine aminotransferase/aspartate aminotransferase (ALT/AST) ≤ 2.5 × ULN or ≤ 5 x ULN in patients with hepatic involvement.
A female patient is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
Not a woman of childbearing potential (WOCBP) OR A WOCBP who agrees to use highly effective contraceptive methods during the treatment period and for at least 180 days after the last dose of study treatment and refrain from egg donation during this period.
A male patient must agree to use a contraceptive during the treatment period and for at least 180 days after the last dose of study treatment and refrain from donating sperm during this period.
Cohorts 1b, 2a, 2c, 3 and 4a:
Ability to comprehend and willingness to provide written informed consent (ICF) for the study.
Age ≥ 18 years.

You may not qualify if…

All Cohorts:
Unwilling or unable to follow protocol requirements or to give informed consent.
Gastro-intestinal bowel obstruction (partial or complete).
Participation in any other study with an investigational study drug or device requires Medical Monitor approval.
Prior monoclonal antibody within 4 weeks or 5 half-lives (whichever is shorter) before administration of study treatment with the exception of bevacizumab (Avastin®), cetuximab (Erbitux®) and panitumumab (Vectibix®) which may have been received within 15 days from initiation of study treatment. Supportive care (e.g. denosumab) may be used before and during study treatment.
Prior therapy with checkpoint inhibitors (anti-programmed death 1 (anti-PD-1), anti-programmed death-ligand 1 (anti-PD-L1), anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4)). Patients must not have received any investigational immunotherapy neither.
Prior chemotherapy or targeted small molecule therapy within 15 days from initiation of study treatment.
Prior radiotherapy within 2 weeks of enrolment or within 4 weeks of enrolment in the case of radiation to central nervous system (CNS), which requires ≥ 4-week washout. Patients must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis.
Major (according the Investigator's judgment) surgery within 12 weeks before enrolment.
Known additional malignancy that is progressing or requires active treatment, or history of other malignancy within 2 years of study entry with the exception of cured basal cell or squamous cell carcinoma of the skin, superficial bladder cancer, prostate intraepithelial neoplasm, carcinoma in situ of the cervix, ductal or lobular carcinoma in situ of the breast, or other non-invasive or indolent malignancy, or cancers from which the patient has been disease-free for > 1 year, after treatment with curative intent.
Immunosuppression including the continued use of systemic (at prednisone dose equivalent of > 10 mg) or topical steroids at or near the injection site (excluding inhaled and eye drop-containing corticosteroids) or the use of immunosuppressive agents for any concurrent condition. All other corticosteroids must be discontinued > 4 weeks prior to first study treatment administration.
Previous vaccination (either therapeutic and/or prophylactic) against mCRC.
Pregnant/nursing women or unwilling to comply with acceptable contraceptive methods during study course.
History of autoimmune disease including any active autoimmune disease except vitiligo or childhood asthma.
Dermatological disease requiring local immunosuppressive agent.
Chronic or concurrent active infectious disease requiring systemic antibodies, antifungal, or antiviral treatment.
Known medical history of human immunodeficiency virus (HIV) infection or known medical history of acquired immunodeficiency syndrome (AIDS). HIV testing is not required unless mandated by the local health authority.
Has known history of or is positive for hepatitis B (hepatitis B virus surface antigen [HBsAg] reactive) or hepatitis C (HCV RNA).
Note: Testing must be performed to determine eligibility. - Hepatitis B virus DNA must be undetectable and HBsAg negative at screening visit.- Hepatitis C antibody testing is allowed for screening purposes in countries where HCV RNA is not part of standard of care. In these cases, HCV antibody positive patients will be excluded.- Patients who have had definitive treatment for HCV are permitted if HCV RNA is undetectable at screening visit.
Known active CNS metastasis and/or carcinomatous meningitis.
Known cerebral oedema.
Live vaccine received within 30 days before initiation of study treatment. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox, yellow fever, rabies, Bacillus Calmette-Guérin, and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed. however, intranasal influenza vaccines (FluMist®) are live attenuated vaccines and are not allowed. COVID-19 vaccines that are not live vaccines are allowed before and during study treatment. However, a COVID-19 vaccination should not occur within ± 2 days of ATP128 study drug and ± 15 days of VSV-GP128 study drug.
History of allergy or hypersensitivity to any of the study drugs or study drug components.
Any condition in the judgment of the Investigator which makes the patient unsuitable for trial participation.
Cohorts 1b, 2a, 2b, 2c, 3, 4a and 4b:

Where it is running

Honor Health Institute — Scottsdale, Arizona, United States
University of Southern California — Los Angeles, California, United States
University of Colorado Anschutz Medical Campus — Aurora, Colorado, United States
NYU Langone Health — New York, New York, United States
Weill Cornell Medicine — New York, New York, United States
Duke Cancer Institute — Durham, North Carolina, United States
University of Texas, MD Anderson Cancer Center — Houston, Texas, United States
University Hospital Antwerpen — Edegem, Belgium
University Hospital Leuven — Leuven, Belgium
University Medicine Mainz — Mainz, Germany
University Hospital Zurich — Zurich, Canton of Zurich, Switzerland
Geneva University Hospitals — Geneva, Switzerland

Full record on ClinicalTrials.gov

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