RP2/RP3 + Atezolizumab + Bevacizumab for Colorectal Cancer

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new combination of treatments for individuals with advanced colorectal cancer that is difficult to treat and has not responded well to other therapies. The study tests an oncolytic immunotherapy, RP2 or RP3, combined with atezolizumab (Tecentriq) and bevacizumab (Avastin), to determine if it can effectively stop or slow the cancer. Suitable candidates have colorectal cancer that has spread or cannot be surgically removed, have tried treatments like irinotecan and oxaliplatin without success, and have at least one measurable and injectable tumor. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group, offering a chance to contribute to significant advancements in cancer therapy.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that RP2 and RP3, when combined with atezolizumab and bevacizumab, have been safe in earlier studies. RP2 and RP3 use viruses to locate and destroy cancer cells. Previous studies have found these therapies to be generally well-tolerated by patients with solid tumors. While side effects can occur, they are usually manageable.

Atezolizumab and bevacizumab are already used in cancer treatment, providing a solid understanding of their safety. Atezolizumab boosts the immune system to fight cancer, while bevacizumab inhibits the growth of blood vessels that feed tumors. Together, they have improved outcomes in various cancers, such as colorectal cancer.

Overall, research supports that this combination of treatments is safe and tolerable, with side effects that are typically controllable. However, anyone considering joining a trial should discuss the potential risks and benefits with their healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of RP2 or RP3 with atezolizumab and bevacizumab for advanced colorectal cancer because these treatments target tumors in a unique way. Unlike standard treatments like chemotherapy or targeted therapies, RP2 and RP3 are delivered directly into tumors through injections, which can be done using a colonoscope or imaging guidance. This targeted delivery aims to boost the immune system's response right at the tumor site, potentially improving effectiveness and reducing side effects compared to systemic treatments. Additionally, pairing these with atezolizumab, an immunotherapy drug, and bevacizumab, which inhibits blood vessel growth in tumors, offers a comprehensive attack on cancer cells, which could lead to better outcomes for patients.

What evidence suggests that this trial's treatments could be effective for colorectal cancer?

This trial will evaluate the effectiveness of two separate treatment combinations for advanced colorectal cancer. One group of participants will receive RP2 oncolytic immunotherapy with atezolizumab and bevacizumab. Another group will receive RP3 oncolytic immunotherapy with the same combination. Studies have shown that using RP2 or RP3 with these drugs can be effective for patients with solid tumors, such as colorectal cancer. Research indicates that this combination treatment has allowed patients to live without their cancer worsening for about 110 days on average and to live overall for about 367 days. This suggests that patients with advanced colorectal cancer, which is stable and has normal DNA repair, could benefit from this treatment. Previous studies also show that using atezolizumab, which helps the immune system fight cancer, along with bevacizumab, improves survival rates for patients with colorectal cancer that has spread. Although still under investigation, this combination of treatments shows promise in fighting this type of cancer. ^{1 2 3 5 6}

Who Is on the Research Team?

May Cho, MD

Principal Investigator

Replimune Inc.

Are You a Good Fit for This Trial?

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.

Women of childbearing potential must have a negative serum beta-human chorionic human chorionic gonadotropin (β-hCG) test with a minimum sensitivity of 25 IU/L or equivalent units of β-hCG within 72 hours before the first dose and a negative urine pregnancy test on D-1

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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 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]

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]

Citations

1. asco.org asco.org/abstracts-presentations/ABSTRACT432908

An open-label clinical trial of RP2 and RP3 oncolytic ... An open-label clinical trial of RP2 and RP3 oncolytic immunotherapy in combination with atezolizumab plus bevacizumab for the treatment of patients with ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05733611

Study Details | NCT05733611 | RP2/RP3 in Combination ... This study will evaluate whether the use of oncolytic immunotherapy, either with RP2 or RP3, can provide meaningful efficacy in combination with an anti-PD-L1 ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.TPS2704

A phase 1 trial of RP2, a first-in-class, enhanced potency ... A phase 1 trial of RP2, a first-in-class, enhanced potency oncolytic HSV expressing an anti-CTLA-4 antibody as a single agent and combined with nivolumab in ...

4. annalsofoncology.org annalsofoncology.org/article/S0923-7534(23)00256-9/pdf

Clinical trial identification This open-label, nonrandomized, phase 2 study will evaluate safety and efficacy of RP2 or RP3 in combination with atezolizumab and bevacizumab in patients with ...

5. fightcolorectalcancer.org fightcolorectalcancer.org/clinical-trial/nct05733611/

RP2/RP3 in Combination With Atezolizumab and ... Inclusion Criteria: 1. Male or female ≥18 years of age. 2. Histological or cytologic diagnosis of colorectal adenocarcinoma that is unresectable or metastatic.

6. researchgate.net researchgate.net/publication/377604496_An_open-label_clinical_trial_of_RP2_and_RP3_oncolytic_immunotherapy_in_combination_with_atezolizumab_plus_bevacizumab_for_the_treatment_of_patients_with_advanced_colorectal_carcinoma

An open-label clinical trial of RP2 and RP3 oncolytic ... This study will evaluate the safety and activity of RP2 and RP3 in combination with atezolizumab (Atezo) plus bevacizumab (Bev) in pts with advanced MSS/pMMR ...