PolyPEPI1018 Vaccine and CDx for the Treatment of Metastatic Colorectal Cancer (OBERTO)

NCT03391232 | Completed Phase 1 Results FDA Drug

• 1 other identifier: OBERTO 101
• Study Type: interventional
• Target: 11
• Locations: 2 countries
• Sites: 2

Brief Summary

Phase I/II clinical trial investigates the safety, tolerability, immunogenicity and preliminary efficacy of multiple doses of PolyPEPI1018 CRC vaccine as an add-on treatment to the standard-of-care maintenance therapy in patients with metastatic colorectal cancer. Clinical responses will be evaluated by indiction of T cell responses, T lymphocyte infiltration in accessible biopsy sites, and by objective tumor responses. This study will also explore the accuracy of the predicted T cell responses in each patient using the candidate companion diagnostic test and the correlations between clinical responses and predicted T cell responses.

Conditions

Colorectal Cancer

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Treatment Related Adverse Events

  Occurrence of at least 1 ≥Grade 4 local adverse event (AE) or 1 ≥Grade 3 systemic AE and/or signs/symptoms, lab toxicities, and/or clinical events that is probably or definitely related to study treatment

  from 1st vaccination to 21 days after last vaccinations, up to 41 weeks

Secondary Outcomes (2)

• Number of Participants Having T Cell Immune Response

  12 weeks

• Number of Predicted Antigen Specific T Cell Responses Per Patient

  21 days

Other Outcomes (3)

• Number of Participants With Objective Tumor Responses - Objective Response Rate (RECIST v1.1)

  12 weeks

• Number of Participants With Objective Tumor Responses - Disease Control Rate (Best Overall Response is Partial Response or Stable Disease)

  12 weeks

• Number of Participants Having Induced Recruitment of TILs

  Last visit, up to 38 weeks

Study Arms (1)

PolyPEPI1018 CRC Vaccine

EXPERIMENTAL

The vaccine contains 6 synthetic peptides mixed with the adjuvant Montanide™. The peptides were selected to induce T cell responses against 12 dominant epitopes from 7 cancer testis antigens (CTAs), which are the most frequently expressed CTAs in colorectal cancer. The 6 peptides were optimized to induce long lasting CRC specific T cell responses.

Biological: PolyPEPI1018 CRC Vaccine

Interventions

PolyPEPI1018 CRC Vaccine BIOLOGICAL

Colorectal Cancer Vaccine

PolyPEPI1018 CRC Vaccine

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female subjects, 18-75 years of age at time of Screening who provide written informed consent prior to initiation of any study procedure
• Histologically confirmed metastatic adenocarcinoma originating from the colon or the rectum
• Presence of at least 1 measurable reference lesion according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria
• Experienced PR or stable disease during first-line treatment with a systemic chemotherapy regimen and 1 biological therapy regimen
• Maintenance therapy with a fluoropyrimidine (5-fluorouracil or capecitabine) plus the same biologic agent (bevacizumab, cetuximab or panitumumab) used during induction, scheduled to initiate prior to the first day of treatment with the study drug
• No more than 1 line of chemotherapy regimen for mCRC (adjuvant therapy for non-metastasized disease is allowed if terminated more than 6 months before Screening and without recurrence within 6 months after the end of adjuvant treatment)
• Last CT scan at 3 weeks or less before the first day of treatment
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Women of childbearing potential must agree to appropriately use an effective form of contraception (failure rate of \<1% per year) for 3 months from the day of the treatment. An effective form of contraception is defined as using hormonal contraceptives or an intrauterine device combined with at least 1 of the following forms of contraception: a diaphragm, cervical cap or condom
• Men must agree to use an effective form of contraception (as defined above), and not donate sperm for 3 months from the day of the treatment
• White blood cell count ≥3.0 × 109/L with neutrophils ≥1.5 × 109/L
• Platelets ≥100 × 109/L, hemoglobin ≥5.6 mmol/L (corresponding to 9 g/dL)
• Serum bilirubin ≤1.5 × upper limit of normal (ULN) set by the site
• Alanine amino transferase (ALAT) and aspartate amino transferase (ASAT) ≤2.5 × ULN in the absence of liver metastases. ALAT and ASAT ≤5 × ULN set by the site in the presence of liver metastases
• Serum creatinine ≤1.5 × ULN set by the site and creatinine clearance \>30 mL/min using Cockroft formula

You may not qualify if:

• Received chronic systemic immune therapy or immunosuppressant medication other than steroids within the last 6 weeks prior to start of study treatment
• Received continuous systemic steroid treatment within the last 2 weeks prior to start of study treatment
• Colorectal cancer with documented high microsatellite instability (MSI-H)
• Colorectal cancer with documented BRAF mutations
• Pre-existing systemic autoimmune or antibody-mediated diseases or immune deficiency diseases
• Central nervous system (CNS) metastases
• Active or uncontrolled severe infections or undiagnosed febrile condition \>38ºC
• Acute or subacute intestinal obstruction or history of chronic intestinal inflammatory diseases
• Symptomatic peritoneal carcinomatosis
• Peritonitis
• Serious, non-healing wounds, ulcers or bone fractures
• Nephrotic syndrome
• Arterial thromboembolisms or severe hemorrhages within 6 months before study enrolment (except bleeding tumor before tumor resection surgery)
• Hemorrhagic diathesis or thrombotic tendency
• Major surgery or radiotherapy within 12 weeks prior to the study treatment or anticipation of needing such procedure during the study period

Sponsors & Collaborators

• Treos Bio Zrt: lead
• Mayo Clinic: collaborator
• University of Pisa: collaborator
• Laboratory Corporation of America: collaborator
• PPD Development, LP: collaborator
• ImmunXperts SA: collaborator

Study Sites (2)

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Universiti di Pisa

Pisa, PI, Italy

Location

Related Publications (1)

• Hubbard JM, Toke ER, Moretto R, Graham RP, Youssoufian H, Lorincz O, Molnar L, Csiszovszki Z, Mitchell JL, Wessling J, Toth J, Cremolini C. Safety and Activity of PolyPEPI1018 Combined with Maintenance Therapy in Metastatic Colorectal Cancer: an Open-Label, Multicenter, Phase Ib Study. Clin Cancer Res. 2022 Jul 1;28(13):2818-2829. doi: 10.1158/1078-0432.CCR-22-0112.

  PMID: 35472243 DERIVED

Related Links

• Treos Bio uses novel biomarkers to develop personalized and off-the-shelf cancer vaccines

MeSH Terms

Conditions

Colorectal 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

Results Point of Contact

• Title: Chef Scientific Officer
• Organization: Treos Bio

eniko.toke@treosbio.com

+3615500826

Study Officials

• Eva Vegh, MD, MDA

  Treos Bio Zrt

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 19, 2017
• First Posted: January 5, 2018
• Study Start: May 3, 2018
• Primary Completion: July 17, 2019
• Study Completion: July 17, 2019
• Last Updated: May 26, 2022
• Results First Posted: April 14, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1); US (1)