RP2/RP3 + Atezolizumab + Bevacizumab for Colorectal Cancer

Recruiting at 24 trial locations

Overseen By Clinical Trials at Replimune

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Replimune Inc.

Must not be taking: Antivirals, Immunosuppressants

Disqualifiers: Hepatitis, HIV, 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: Unknown

Duration: Up to 3 years

4 Participants Needed

Trial Summary

What is the purpose of this trial?

This is an open-label, Phase 2 clinical trial evaluating therapy with an oncolytic immunotherapy (RP2 or RP3) in combination with atezolizumab and bevacizumab in patients with advanced Microsatellite Stable and Mismatch Repair Proficient Colorectal Carcinoma.

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, it does mention that patients on certain anticoagulants or those requiring systemic antivirals may have restrictions. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug combination Atezolizumab, Bevacizumab, and RP2/RP3 for colorectal cancer?

Research shows that Bevacizumab, when combined with chemotherapy, significantly improves survival in patients with metastatic colorectal cancer. Additionally, Bevacizumab has shown potential benefits when used with other drugs, suggesting it could be effective in combination with Atezolizumab and RP2/RP3. ^{1 2 3 4 5}

What makes the RP2/RP3 + Atezolizumab + Bevacizumab treatment unique for colorectal cancer?

This treatment is unique because it combines traditional cancer drugs like Atezolizumab (an immune checkpoint inhibitor) and Bevacizumab (which blocks blood vessel growth in tumors) with RP2 and RP3, which are enhanced oncolytic viruses designed to selectively infect and kill cancer cells, potentially offering a novel approach to treating colorectal cancer. ^{2 3 6 7 8}

Research Team

May Cho, MD

Principal Investigator

Replimune Inc.

Eligibility Criteria

Adults with advanced colorectal cancer that's spread or can't be removed by surgery, who've had progression after treatment with irinotecan and oxaliplatin. They must have a measurable tumor, adequate organ function, agree to use effective contraception if of childbearing potential, and not have other active cancers or significant heart disease.

Inclusion Criteria

Capable of giving signed informed consent which includes willingness to comply with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol

My colorectal cancer cannot be removed by surgery or has spread.

I am 18 years old or older.

Exclusion Criteria

Had a significant bleeding event within the last 12 months that places the patient at unjustifiable risk for bleeding from deep intratumoral injection procedures based on Investigator assessment or interventional radiologist assessment

I am HIV positive.

I have not received a live vaccine in the last 28 days.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive oncolytic immunotherapy (RP2 or RP3) in combination with atezolizumab and bevacizumab

Up to 3 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

60 days after last dose of RP2/RP3, or 135 days after last dose of atezolizumab/bevacizumab

Treatment Details

Interventions

• Atezolizumab
• Bevacizumab
• RP2
• RP3

Trial Overview The trial is testing the combination of RP2/RP3 oncolytic immunotherapies with atezolizumab (a drug that helps the immune system fight cancer) and bevacizumab (which inhibits blood vessel growth in tumors), for patients whose colorectal cancer has resisted standard treatments.

Participant Groups

Group I: RP3 and atezolizumab plus bevacizumab in advanced MSS and pMMR CRC Experimental Treatment 3 Interventions

RP3 will be injected by direct (including via colonoscope) or image-guided injection into injectable tumors (including subcutaneous, visceral, and nodal tumors).

Group II: RP2 and atezolizumab plus bevacizumab in advanced MSS and pMMR CRC Experimental Treatment 3 Interventions

RP2 will be injected by direct (including via colonoscope) or image-guided injection into injectable tumors (including subcutaneous, visceral, and nodal tumors).

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?

Replimune Inc.

Lead Sponsor

Trials

16

Recruited

1,700+

Roche Pharma AG

Industry Sponsor

Trials

413

Recruited

430,000+

Dr. Thomas Schinecker

Roche Pharma AG

Chief Executive Officer since 2023

PhD in Molecular Biology from New York University

Dr. Levi Garraway

Roche Pharma AG

Chief Medical Officer since 2019

MD from University of California, San Francisco

Findings from Research

In a phase IV trial involving 209 treatment-naïve patients with metastatic colorectal cancer, the combination of bevacizumab and FOLFIRI resulted in a median progression-free survival (PFS) of 11.1 months and a median overall survival (OS) of 22.2 months, demonstrating its efficacy as a first-line treatment.

The treatment was generally well-tolerated, with most adverse events being mild (grade 1/2), while serious side effects like neutropenia and venous thromboembolic events occurred in over 10% of patients, indicating manageable safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase IV study of bevacizumab in combination with infusional fluorouracil, leucovorin and irinotecan (FOLFIRI) in first-line metastatic colorectal cancer. Sobrero, A., Ackland, S., Clarke, S., et al.[2022]

Bevacizumab (Avastin) significantly improves overall and progression-free survival in patients with metastatic colorectal cancer when combined with standard chemotherapy regimens like IFL or 5-FU/LV, based on clinical data from various trials.

The drug shows potential for use in both first-line and second-line treatments, as well as in the adjuvant setting, by inhibiting vascular endothelial growth factor to prevent tumor angiogenesis, with ongoing Phase III trials exploring its efficacy in combination with oxaliplatin-based therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The future development of bevacizumab in colorectal cancer. Díaz-Rubio, E., Schmoll, HJ.[2015]

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 II trial involving 44 patients with refractory metastatic colorectal cancer, the combination of bevacizumab, S-1, and raltitrexed demonstrated a 15.9% objective response rate and a disease control rate of 54.5%, indicating potential effectiveness in this challenging patient population.

The treatment was well tolerated, with a median progression-free survival of 110 days and overall survival of 367 days, suggesting that this combination therapy could be a viable option for patients who have not responded to standard treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab Combined with S-1 and Raltitrexed for Patients with Metastatic Colorectal Cancer Refractory to Standard Therapies: A Phase II Study. Chen, Y., Zhou, YW., Cheng, K., et al.[2021]

Bevacizumab, an anti-angiogenic monoclonal antibody, has been shown to extend survival in patients with metastatic colorectal cancer when used alongside chemotherapy.

Recent studies suggest that combining bevacizumab with oxaliplatin-containing chemotherapy regimens may further enhance patient outcomes, indicating a potential strategy for improving treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab plus oxaliplatin-based regimens for the treatment of colorectal cancer. Scheithauer, W., Schmiegel, W.[2018]

In a randomized phase II trial involving 255 patients with metastatic colorectal cancer, both capecitabine/oxaliplatin (CapOx) plus bevacizumab and dose-modified capecitabine/irinotecan (mCapIri) plus bevacizumab demonstrated promising efficacy, with 6-month progression-free survival rates of 76% and 84%, respectively.

Both treatment regimens had manageable safety profiles, with grade 3/4 diarrhea occurring in 22% of patients receiving CapOx and 16% receiving mCapIri, indicating that these combinations are effective and have acceptable toxicity levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Capecitabine/irinotecan or capecitabine/oxaliplatin in combination with bevacizumab is effective and safe as first-line therapy for metastatic colorectal cancer: a randomized phase II study of the AIO colorectal study group. Schmiegel, W., Reinacher-Schick, A., Arnold, D., et al.[2020]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Phase IV study of bevacizumab in combination with infusional fluorouracil, leucovorin and irinotecan (FOLFIRI) in first-line metastatic colorectal cancer. [2022]

2. Switzerland pubmed.ncbi.nlm.nih.gov

The future development of bevacizumab in colorectal cancer. [2015]

3. 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]

4. England pubmed.ncbi.nlm.nih.gov

Bevacizumab Combined with S-1 and Raltitrexed for Patients with Metastatic Colorectal Cancer Refractory to Standard Therapies: A Phase II Study. [2021]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Bevacizumab plus oxaliplatin-based regimens for the treatment of colorectal cancer. [2018]

6. England pubmed.ncbi.nlm.nih.gov

Capecitabine/irinotecan or capecitabine/oxaliplatin in combination with bevacizumab is effective and safe as first-line therapy for metastatic colorectal cancer: a randomized phase II study of the AIO colorectal study group. [2020]

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

Dual VEGF inhibition with sorafenib and bevacizumab as salvage therapy in metastatic colorectal cancer: results of the phase II North Central Cancer Treatment Group study N054C (Alliance). [2022]

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

Correlation of lactate dehydrogenase isoenzyme profile with outcome in patients with advanced colorectal cancer treated with chemotherapy and bevacizumab or cediranib: Retrospective analysis of the HORIZON I study. [2015]