Phase 1b Study to Evaluate ATP128, VSV-GP128 and BI 754091, in Patients With Stage IV Colorectal … (NCT04046445) | Clinical Trial Compass
Active — Not RecruitingPhase 1
Phase 1b Study to Evaluate ATP128, VSV-GP128 and BI 754091, in Patients With Stage IV Colorectal Cancer
United States96 participantsStarted 2019-07-22
Plain-language 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
Who can participate
Age range18 Years
SexALL
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Inclusion criteria
✓. 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.
Exclusion criteria
✕
What they're measuring
1
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
Timeframe: 1 year
2
valuate anti-tumor effect of study treatment by measure of Progression-free survival (PFS)
. 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.