PolyPEPI1018 + Atezolizumab for Colorectal Cancer

Recruiting at 3 trial locations

Overseen By Eniko R Toke, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Treos Bio Limited

Must not be taking: Checkpoint inhibitors, Corticosteroids

Disqualifiers: Autoimmune diseases, CNS metastases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 3

Duration: Up to 3 years

18 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have received certain anticancer therapies, live vaccines, or systemic corticosteroids shortly before starting the trial. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug Atezolizumab for colorectal cancer?

Atezolizumab, when combined with other treatments, has shown encouraging activity in early studies for a small group of colorectal cancer patients with a specific genetic feature (dMMR). However, more research is needed to confirm its effectiveness for a broader group of patients. ^{1 2 3 4 5}

What makes the drug combination of PolyPEPI1018 and Atezolizumab unique for colorectal cancer?

The combination of PolyPEPI1018 and Atezolizumab is unique because it targets the immune system to fight colorectal cancer, specifically by blocking PD-L1, a protein that helps cancer cells evade the immune system. This approach is particularly promising for patients with a specific genetic makeup (dMMR) that makes them more responsive to immune checkpoint inhibitors like Atezolizumab. ^{1 3 4 6 7}

Research Team

Joleen M Hubbard

Principal Investigator

Mayo Clinic

Hagop Youssoufian, MD

Principal Investigator

Treos Bio Ltd.

Eligibility Criteria

Adults over 18 with metastatic colorectal cancer (MSS CRC) who have tried and progressed on 2-3 prior treatments can join this trial. They must be in good physical condition, not pregnant or breastfeeding, willing to undergo biopsies and provide consent. Excluded are those with autoimmune diseases, recent vaccines or surgeries, active infections like HIV/HBV/HCV, CNS metastases, history of severe allergies to vaccines or proteins.

Inclusion Criteria

I am fully active or can carry out light work.

I am not pregnant, not breastfeeding, and meet one of the required conditions.

I agree to have a biopsy before and 6 weeks after starting the study therapy, or I have tissue samples available from the last 3 months.

Exclusion Criteria

My liver condition is severe.

You have a history of an autoimmune disease.

Pregnant or breast-feeding or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 90 days after the last dose of study treatment

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive PolyPEPI1018 vaccine and atezolizumab every 3 weeks until documented progression

Up to 3 years

Every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

90 days after last dose

Long-term follow-up

Participants are monitored for overall survival and progression-free survival

Up to 3 years

Treatment Details

Interventions

• Atezolizumab
• PolyPEPI1018

Trial Overview The trial is testing the combination of a new vaccine called PolyPEPI1018 with an existing cancer drug Atezolizumab in patients whose colorectal cancer has worsened after previous treatments. It's an open-label phase II study focusing on safety and how well the body responds to this combo.

Participant Groups

Group I: PolyPEPI1018 plus Atezolizumab Experimental Treatment 2 Interventions

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.

Atezolizumab is already approved in United States, European Union for the following indications:

Approved in United States as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

Approved in European Union as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

Who Is Running the Clinical Trial?

Treos Bio Limited

Lead Sponsor

Trials

1

Recruited

20+

Mayo Clinic

Collaborator

Trials

3,427

Recruited

3,221,000+

Hoffmann-La Roche

Industry Sponsor

Trials

2,482

Recruited

1,107,000+

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Avastin, Herceptin, Rituxan, Accu-Chek

Dr. Levi Garraway

Hoffmann-La Roche

Chief Medical Officer since 2019

MD from the University of Basel

Dr. Thomas Schinecker

Hoffmann-La Roche

Chief Executive Officer since 2023

PhD in Molecular Biology from New York University

Findings from Research

Atezolizumab is a monoclonal antibody that targets PD-L1, which is being developed for treating various blood cancers and solid tumors, showing promise in cancer immunotherapy.

It has already been approved in the US as a second-line treatment for urothelial carcinoma and is pending approval for non-small cell lung cancer, highlighting its potential efficacy in these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab: First Global Approval. Markham, A.[2019]

In a phase II/III trial involving 397 patients with metastatic colorectal cancer, the combination of trifluridine/tipiracil (FTD/TPI) and bevacizumab did not show noninferiority compared to the standard treatment of fluoropyrimidine and irinotecan plus bevacizumab, with a median overall survival of 14.8 months versus 18.1 months, respectively.

Patients receiving FTD/TPI plus bevacizumab experienced a higher rate of grade ≥3 adverse events, particularly neutropenia (65.8% vs. 41.6% in the control group), indicating potential safety concerns with this treatment combination.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trifluridine/tipiracil+bevacizumab (BEV) vs. fluoropyrimidine-irinotecan+BEV as second-line therapy for metastatic colorectal cancer: a randomised noninferiority trial. Kuboki, Y., Terazawa, T., Masuishi, T., et al.[2023]

Atezolizumab, a monoclonal antibody targeting PD-L1, shows promising efficacy in treating metastatic colorectal cancer (mCRC), particularly in patients with deficient mismatch repair (dMMR), indicating a potential new treatment avenue for this subgroup.

Ongoing clinical trials suggest that atezolizumab may be even more effective when combined with chemotherapy or targeted therapies, such as the MEK inhibitor cobimetinib, paving the way for its inclusion in future treatment protocols for mCRC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab for the treatment of colorectal cancer: the latest evidence and clinical potential. Tapia Rico, G., Price, TJ.[2022]

In a phase 2 clinical trial involving 133 patients with refractory metastatic colorectal cancer, the addition of atezolizumab to capecitabine and bevacizumab therapy resulted in a median progression-free survival (PFS) of 4.4 months compared to 3.6 months for the placebo group, indicating a potential benefit, although not clinically meaningful.

Patients with microsatellite-stable disease and those without liver metastasis showed greater benefits from the combination therapy, suggesting that specific patient characteristics may influence the efficacy of atezolizumab in this treatment context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of Capecitabine and Bevacizumab With or Without Atezolizumab for the Treatment of Refractory Metastatic Colorectal Cancer: A Randomized Clinical Trial. Mettu, NB., Ou, FS., Zemla, TJ., et al.[2022]

In a phase 2 study involving 218 patients with previously untreated metastatic colorectal cancer, the addition of atezolizumab to the standard chemotherapy regimen (FOLFOXIRI plus bevacizumab) significantly improved median progression-free survival to 13.1 months compared to 11.5 months in the control group.

The treatment was found to be safe, with the most common serious side effects being neutropenia and diarrhoea, although there were two treatment-related deaths in the atezolizumab group, indicating a need for careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Upfront FOLFOXIRI plus bevacizumab with or without atezolizumab in the treatment of patients with metastatic colorectal cancer (AtezoTRIBE): a multicentre, open-label, randomised, controlled, phase 2 trial. Antoniotti, C., Rossini, D., Pietrantonio, F., et al.[2022]

Atezolizumab is an FDA-approved treatment for advanced bladder cancer that works by blocking the PD-L1/PD-1 immune checkpoint, enhancing T-cell immunity against tumors.

In clinical trials, atezolizumab showed a 15% objective response rate in patients whose cancer progressed after chemotherapy, and a 24% response rate in chemotherapy-naïve patients, with a favorable safety profile compared to other second-line treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab: A PD-L1-Blocking Antibody for Bladder Cancer. Inman, BA., Longo, TA., Ramalingam, S., et al.[2022]

Atezolizumab, the first anti-PD-L1 monoclonal antibody approved by the FDA, has shown promising efficacy in treating metastatic triple-negative breast cancer, supported by data from the Phase III IMpassion130 trial.

The review highlights the pharmacodynamic and pharmacokinetic properties of atezolizumab, emphasizing its safety and effectiveness in various cancers, including small-cell lung cancer and renal cell cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab for use in PD-L1-positive unresectable, locally advanced or metastatic triple-negative breast cancer. Mavratzas, A., Seitz, J., Smetanay, K., et al.[2020]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Atezolizumab: First Global Approval. [2019]

2. England pubmed.ncbi.nlm.nih.gov

Trifluridine/tipiracil+bevacizumab (BEV) vs. fluoropyrimidine-irinotecan+BEV as second-line therapy for metastatic colorectal cancer: a randomised noninferiority trial. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Atezolizumab for the treatment of colorectal cancer: the latest evidence and clinical potential. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Assessment of Capecitabine and Bevacizumab With or Without Atezolizumab for the Treatment of Refractory Metastatic Colorectal Cancer: A Randomized Clinical Trial. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Upfront FOLFOXIRI plus bevacizumab with or without atezolizumab in the treatment of patients with metastatic colorectal cancer (AtezoTRIBE): a multicentre, open-label, randomised, controlled, phase 2 trial. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Atezolizumab: A PD-L1-Blocking Antibody for Bladder Cancer. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Atezolizumab for use in PD-L1-positive unresectable, locally advanced or metastatic triple-negative breast cancer. [2020]