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

NCT04046445 | Active Not Recruiting Phase 1 FDA Drug

• 3 other identifiers: KISIMA-012019-000728-162021DR1011
• Study Type: interventional
• Target: 96
• Locations: 4 countries
• Sites: 12

Brief Summary

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

Conditions

Colorectal Cancer; MSS; Stage IV Colon Cancer; Stage IV Rectal Cancer; Metastatic Colorectal Cancer; Liver Metastasis Colon Cancer

Keywords

CRC; Colorectal Cancer; MSS; Metastatic Colorectal Cancer; Liver Metastasis Colon Cancer; Stage IV Colon Cancer; Stage IV Rectal Cancer; KISIMA-01; ATP128; BI 754091 (Ezabenlimab); MMRp; VSV-GP128; Therapeutic viral vaccine; Heterologous prime-boost; Maintenance setting

Outcome Measures

Primary Outcomes (2)

• Evaluate safety and tolerability by measure of incidence of treatment-emergent adverse events (AEs) and serious adverse events (SAEs) graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0

  Safety

  1 year

• valuate anti-tumor effect of study treatment by measure of Progression-free survival (PFS)

  Based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1

  6 months

Secondary Outcomes (6)

• Evaluate anti-tumor effect of study treatment by measure of Overall Response (OR)

  1 year

• Confirm recommended phase 2 dose (RP2D) of study treatment

  1 year

• Further evaluate anti-tumor effect of study treatment of Best Overall Response (BOR)

  1 year

• Evaluate anti-tumor effect of study treatment by measure of Duration of Response (DoR)

  1 year

• Evaluate anti-tumor effect of study treatment by measure of Progression Free Survival (PFS)

  1 year

Other Outcomes (4)

• Evaluate pharmacodynamic effects of study treatment

  4.5 months

• Detect early signal of relapse in tumor-free patients with liquid biopsy

  6 months

• Further evaluate anti-tumor effect of study treatment by measure of PFS

  1 year

Study Arms (8)

Cohort 1a

EXPERIMENTAL

6 patients with stage IV CRC who failed SoC therapies

Drug: ATP128

Cohort 1b

EXPERIMENTAL

6 patients with stage IV MSS/MMRp CRC in SD or PR after first line of SoC

Drug: ATP128; Drug: BI 754091

Cohort 2a

EXPERIMENTAL

5 patients with stage IV MSS/MMRp CRC in SD or PR after first line of SoC

Drug: ATP128; Drug: BI 754091

Cohort 2b

EXPERIMENTAL

15 patients with stage IV MSS/MMRp CRC with liver-limited disease

Drug: ATP128; Drug: BI 754091

Cohort 2c

EXPERIMENTAL

19 patients with stage IV MSS/MMRp CRC in SD or PR after first line of SoC

Drug: ATP128; Drug: BI 754091

Cohort 3

EXPERIMENTAL

6 patients with stage IV MSS/MMRp CRC in SD or PR after first line of SoC

Drug: ATP128; Drug: BI 754091; Drug: VSV-GP128

Cohort 4a

EXPERIMENTAL

24 patients with stage IV MSS/MMRp CRC in SD or PR after first line of SoC

Drug: ATP128; Drug: BI 754091; Drug: VSV-GP128

Cohort 4b

EXPERIMENTAL

15 patients with stage IV MSS/MMRp CRC with liver-limited disease

Drug: ATP128; Drug: BI 754091; Drug: VSV-GP128

Interventions

ATP128 DRUG

5-6 SC injections

Cohort 1a; Cohort 1b; Cohort 2a; Cohort 2b; Cohort 2c; Cohort 3; Cohort 4a; Cohort 4b

BI 754091 DRUG

≥ 7 IV infusions

Also known as: Ezabenlimab

Cohort 1b; Cohort 2a; Cohort 2b; Cohort 2c; Cohort 3; Cohort 4a; Cohort 4b

VSV-GP128 DRUG

1 single IV injection

Cohort 3; Cohort 4a; Cohort 4b

Eligibility Criteria

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

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.

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.

Sponsors & Collaborators

• Amal Therapeutics: lead
• Boehringer Ingelheim: collaborator

Study Sites (12)

Honor Health Institute

Scottsdale, Arizona, 85258, United States

Location

University of Southern California

Los Angeles, California, 90033, United States

Location

University of Colorado Anschutz Medical Campus

Aurora, Colorado, 80045, United States

Location

NYU Langone Health

New York, New York, 10016, United States

Location

Weill Cornell Medicine

New York, New York, 10065, United States

Location

Duke Cancer Institute

Durham, North Carolina, 27710, United States

Location

University of Texas, MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

University Hospital Antwerpen

Edegem, 2650, Belgium

Location

University Hospital Leuven

Leuven, 3000, Belgium

Location

University Medicine Mainz

Mainz, 55131, Germany

Location

University Hospital Zurich

Zurich, Canton of Zurich, 8006, Switzerland

Location

Geneva University Hospitals

Geneva, 1205, Switzerland

Location

Related Publications (1)

• Namdari H, Rezaei F, Heidarnejad F, Yaghoubzad-Maleki M, Karamigolbaghi M. Immunoinformatics Approach to Design a Chimeric CD70-Peptide Vaccine against Renal Cell Carcinoma. J Immunol Res. 2024 Jan 27;2024:2875635. doi: 10.1155/2024/2875635. eCollection 2024.

  PMID: 38314087 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms; Colonic Neoplasms; Rectal Neoplasms

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Study Officials

• Scott Kopetz

  MD Anderson

  PRINCIPAL INVESTIGATOR

Study Design

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

Model Details: 8 cohorts

Study Record Dates

• First Submitted: July 30, 2019
• First Posted: August 6, 2019
• Study Start: July 22, 2019
• Primary Completion: May 31, 2025
• Study Completion: August 31, 2025
• Last Updated: January 29, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (7); BE (2); DE (1); CH (2)