Safety and Activity of PolyPEPI1018 Plus Atezolizumab in Colorectal Cancer.

NCT05243862 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: OBERTO-301
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 3

Brief Summary

This is a multicenter, open label, phase II trial to determine the safety, tolerability, and immunogenicity and initial clinical activity of the combination treatment of PolyPEPI1018 vaccine and atezolizumab in participants with MSS CRC who have progressed on 2 or 3 prior regimens.

Conditions

Colorectal Cancer Metastatic

Keywords

MSS; Peptide Vaccine; Cancer vaccine; PolyPEPI1018; Checkpoint inhibitor; PD-L1 inhibitor; Atezolizumab

Outcome Measures

Primary Outcomes (2)

• The incidence and severity treatment related Adverse Events

  The incidence and severity \[according to the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0 (v5.0)\] of all adverse events (AEs), related AEs, all SAEs, and related SAEs

  From 1st dose until 90-Days after last dose

• Administration safety

  Number and proportion of participants with any clinically significant change in vital signs (i.e., blood pressure, pulse rate, respiratory rate, body temperature) during the vaccine administration or within 60 minutes following administration

  During the vaccine administration or within 60 minutes following administration

Secondary Outcomes (7)

• Objective Response Rate assessment

  From study entry up to 2 years

• Duration of Response assessment

  From study entry up to 3 years

• Progression Free Survival assessment

  From study entry up to 3 years

• Overall Survival assesment

  From study entry up to 3 years

• PEPI Listing

  1 year

Study Arms (1)

PolyPEPI1018 plus Atezolizumab

EXPERIMENTAL

Participants receive every 3 weeks PolyPEPI1018 CRC Vaccine (Emulsified solution, 0.2 mg/peptide, 6 peptides total, and Montanide™ ISA51VG adjuvant), by SC injection in combination with Atezolizumab (Injectable solution,1200mg/20mL) by IV injection.

Drug: PolyPEPI1018; Drug: Atezolizumab

Interventions

PolyPEPI1018 DRUG

PolyPEPI1018 vaccine contains 6 synthetic peptides emulsified with the adjuvant Montanide™. The peptides were selected to induce T cell responses against 12 dominant epitopes from 7 tumor-specific antigens, which are the most frequently expressed antigens in colorectal cancer.

Also known as: PolyPEPI1018 CRC vaccine

PolyPEPI1018 plus Atezolizumab

Atezolizumab DRUG

Atezolizumab is a fully humanized, engineered monoclonal antibody of IgG1 isotype against the protein programmed cell death-ligand 1.

Also known as: Tecentriq

PolyPEPI1018 plus Atezolizumab

Eligibility Criteria

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

You may qualify if:

• Provide written informed consent for the trial.
• Adults 18 years or older on the day of signing informed consent.
• Histologically or cytologically confirmed CRC that is metastatic.
• Primary and/or metastatic tumor(s) that is known to be MSS as determined locally
• Must have had 2-3 prior lines of therapy for CRC in the advanced or metastatic setting, including all of the following in the absence of contraindications: a) fluoropyrimidine, b) oxaliplatin, c) irinotecan, d) one or more biologics depending on the clinical scenario. Prior regorafenib and/or TAS-102 are allowed but not required. Note: a line of therapy is generally considered \>2 weeks of exposure to the same regimen followed by radiographically documented progression. Agents that are mechanistically similar (e.g. 5-fluorouracil and capecitabine) and are used interchangeably due to tolerability but not progression may be considered as components of the same regimen upon discussion with the medical monitor.
• Willingness to undergo biopsy prior to study therapy and after approximately 6 weeks of study therapy. If biopsy on study is not feasible, then archival tissue must be available from within 90 days of signing consent.
• Willingness to undergo buccal swab prior to study therapy for the determination of HLA profile.
• Documented radiographic progression after the last regimen prior to entry on this study.
• Measurable disease, as defined by RECIST v1.1. Previously irradiated lesions can only be considered as measurable disease if disease progression has been unequivocally documented at that site since radiation.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
• Adequate organ functions as defined by the following laboratory parameters at baseline (laboratory parameters outside of these ranges that are deemed clinically insignificant should be discussed with the medical monitor):
• Absolute neutrophil count ≥1.5 x 109/L;
• Hemoglobin ≥9 g/dL: transfusion to achieve this cutoff is not allowed within 14 days of first dose of study therapy;
• Platelet count ≥100,000/mm3;
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 x upper limit of normal (ULN) - ASL and/or ALT may be ≤5 x ULN in the setting of liver metastases;

You may not qualify if:

• Prior treatment with an anti-CTLA-4, anti-PD-1, anti-PD-L1, anti-PD-L2 or any other checkpoint inhibitors.
• Has received prior anticancer therapy (chemotherapy, targeted therapies, radiotherapy, or immunotherapy) within 28 days of the first dose of study therapy or 5 half-lives (whichever is shorter) if at least 10 days have elapsed between the last dose of such agents and the first dose of study therapy. NOTE: Patients who have been given palliative radiotherapy to peripheral sites (e.g., bone metastases) may enroll before 28 days have elapsed if they have recovered from any acute toxicities.
• Has received a live vaccine within 28 days of the first dose of study therapy.
• Has had major surgical procedure, open biopsy or significant traumatic injury within 28 days of the first dose of study therapy.
• Participating in another research study involving receipt of an investigational product 21 days prior to study therapy.
• History of autoimmune disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis. Note: Patients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone are eligible for this study. Patients with controlled Type I diabetes mellitus on a stable dose of insulin regimen are also eligible for this study.
• Receiving systemic corticosteroids within one week prior to the first dose of study therapy. Exceptions: corticosteroid use as a premedication for intravenous (IV) contrast, intermittent corticosteroid use (e.g., daily prednisone at doses of ≤10 mg or equivalent), bronchodilators, inhaled steroids, or local steroid injections (except at the proposed injection site of PolyPEPI1018) are acceptable.
• History of anaphylaxis in relation to vaccination or the administration of a protein product.
• Has known allergy to any component of the study treatment formulation(s).
• Has symptomatic interstitial lung disease (ILD) or ILD which may interfere with detection and management of new immune-related pulmonary toxicity.
• Prior allogeneic bone marrow transplantation or solid organ transplant.
• Has known, active central nervous system (CNS) metastases and/or leptomeningeal metastases. Patients with previously treated, stable CNS metastases may participate if (a) there is no evidence of progression by imaging \[magnetic resonance imaging (MRI) or computed tomography (CT) as used during the prior imaging\] at least 28 days prior to the first dose of study therapy; (b) resolution or return to baseline of neurologic symptoms; and (c) no requirement for steroids to manage symptoms of brain metastases for at least 28 days prior to first dose of study therapy.
• Active infection requiring systemic therapy.
• Significant liver cirrhosis defined as Child-Pugh Class B or C (Appendix 4).
• Active infection with human immunodeficiency virus (HIV) except participants who are currently stable on antiretroviral therapy (ART) for at least 4 weeks and agree to adhere to ART during study therapy, have HIV viral load of \<400 copies per milliliter (/mL) at screening (or undetectable per local criteria), and have CD4 T cell counts ≥200/microliter.

Sponsors & Collaborators

• Treos Bio Limited: lead
• Mayo Clinic: collaborator
• Hoffmann-La Roche: collaborator

Study Sites (3)

Mayo Clinic

Phoenix, Arizona, 85054, United States

Location

Mayo Clinic

Jacksonville, Florida, 32224, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Related Links

• Evaluation of safety, immunogenicity and preliminary efficacy of PolyPEPI1018 vaccine in subjects with metastatic colorectal cancer (mCRC) with a predictive biomarker
• P329 PolyPEPI1018 off-the shelf vaccine as add-on to maintenance therapy achieved durable treatment responses in patients with microsatellite-stable metastatic colorectal cancer patients (MSS mCRC)

MeSH Terms

Interventions

atezolizumab

Study Officials

• Joleen Hubbard, MD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

• Hagop Youssoufian, MD

  Treos Bio Ltd.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Following the Simon's 2-stage design, 18 participants will be enrolled in the first stage. If no participant with a response is observed, the study will be terminated for futility. If ≥ 1 participants achieve a response, then the study can proceed to the second stage, and additional 10 participants will be enrolled to the second stage.

Study Record Dates

• First Submitted: January 26, 2022
• First Posted: February 17, 2022
• Study Start: June 2, 2022
• Primary Completion: July 8, 2024
• Study Completion: June 2, 2026
• Last Updated: March 18, 2025

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)