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Refractory Metastatic Colorectal CancerPhase 2NCT05733611

RP2/RP3 in Combination With Atezolizumab and Bevacizumab for the Treatment of Patients With CRC

A Phase 2 study testing RP2, RP3 and atezolizumab in people with Refractory Metastatic Colorectal Cancer and pMMR, run by Replimune, Inc. at 2 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Refractory Metastatic Colorectal Cancer, pMMR, MSS
What is being tested?
RP2, RP3 and atezolizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
5 participants
Where
2 sitesUnited States
Study dates
29 Jun 2023to 18 Aug 2025
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Male or female ≥18 years of age.
  • Histological or cytologic diagnosis of colorectal adenocarcinoma that is unresectable or metastatic.
  • Have had disease progression or were intolerant to treatment protocols that included irinotecan and oxaliplatin. Epidermal growth factor receptor (EGFR) or vascular endothelial growth factor receptor (VEGFR) directed therapies are allowed as part of the previous therapy if indicated.
  • Has at least 1 measurable tumor of ≥1 cm in longest diameter (or ≥1.5cm shortest diameter for lymph nodes).
  • Has injectable tumor(s) of at least 1cm in aggregate total diameter.
  • Must be willing to consent to provide archival tumor biopsy samples obtained within 90 days prior to Screening, or a fresh tumor biopsy collected on Day 1 of treatment or earlier.
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  • Has adequate hematologic function, including:
  • White blood cell count ≥2.0 × 10^9/L
  • Absolute neutrophil count ≥1.5 × 10^9/L
  • Platelet count ≥75 × 10^9/L
  • Hemoglobin ≥8 g/dL(transfusions allowed; however, patient must not be transfusion-dependent).
  • Has adequate hepatic function, including:
  • Total bilirubin ≤1.5 × upper limit of normal (ULN; except patients with Gilbert syndrome or liver metastases, who must have a total bilirubin of <2.0 × ULN)
  • Serum albumin ≥2.8 g/dL
  • Aspartate aminotransferase and alanine aminotransferase (ALT)≤3.0 × ULN (or ≤5.0 × ULN, if liver metastases are present).
  • Has adequate renal function, defined as serum creatinine ≤1.5 × ULN or creatinine clearance ≥30 mL/minute (measured using Cockcroft-Gault formula or by 24-hour urine collection).
  • Prothrombin time ≤1.5 × ULN (or international normalization ratio [INR] ≤1.3) and partial thromboplastin time (PTT) or activated partial thromboplastin time (aPTT) ≤1.5×ULN.
  • Note: Patients who are on chronic anticoagulant therapy may be enrolled if the pretreatment INR<2.5. For patients requiring a deep injection of RP2/RP3, the INR must be <1.5 at the time of injection.
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 to 1.
  • Female and male patients of reproductive potential must agree to avoid becoming pregnant or impregnating a partner and adhere to highly effective contraception requirements during the treatment period and for at least (a) 90 days after the last dose of RP2 or RP3 or (b) 5 months after the last dose of atezolizumab or (c) 6 months after the last dose of bevacizumab, whichever is longer.
  • 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.
  • 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.

Who cannot join

  • Prior treatment with regorafenib, trifluridine/tipiracil, fruquintinib, and immunotherapies.
  • Has received more than 3 lines of therapy for CRC.
  • Has microsatellite instability-high (MSI-H)/deficient DNA mismatch repair (dMMR)disease or BRAF V600E mutation.
  • Acute or chronic hepatitis B (defined as hepatitis B surface antigen [HBsAg] reactive) or acute or chronic hepatitis C virus (HCV; defined as HCV RNA [qualitative] is detected).
  • Note: Patients who have been effectively treated are eligible for enrollment. Patients must be negative for HBsAg and HCV RNA.
  • Known human immunodeficiency virus (HIV) infection.
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  • Note: Testing for HIV is not required unless mandated by local health authority or clinically indicated.
  • Had systemic infection requiring intravenous (IV) antibiotics or other serious infection within 14 days prior to dosing.
  • With active significant herpetic infections or prior complications of HSV-1 infection (eg, herpetic keratitis or encephalitis).
  • Note: Patients with sporadic cold sores may be enrolled as long as no active cold sores are present at the time of Day 1
  • Active or history of central nervous system (CNS) metastases and/or carcinomatous meningitis.
  • Prior malignancy active within the previous 3 years, except for locally curable cancers that have apparently been cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast.
  • Macroscopic intravascular invasion into any large blood vessel such as the main portal vein, hepatic vein, pulmonary arteries or veins, aorta, or vena cava.
  • 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.
  • History of significant cardiac vascular disease including myocarditis or congestive heart failure (defined as New York Heart Association Functional Classification III or IV), or unstable angina, serious uncontrolled cardiac arrhythmia, or myocardial infarction within 6 months of randomization.
  • Uncontrolled infection.
  • History or evidence of psychiatric disease, substance abuse, or any other clinically significant disorder, condition, or disease (with the exception of those outlined above) that, in the opinion of the Investigator or the Medical Monitor, would pose a risk to patient safety or interfere with the study evaluation, procedures, or completion.
  • History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study, or is not in the best interest of the patient to participate, in the opinion of the treating Investigator
  • Active, known, or suspected autoimmune disease such as autoimmune thyroiditis and colitis requiring systemic immunomodulatory treatment. Note: Patients with diabetes mellitus, dysthyroidism without an autoimmune mechanism, and rheumatoid arthritis that do not require immunomodulatory treatment are permitted to enroll.
  • History of drug-induced interstitial lung disease, (noninfectious) pneumonitis that required steroids, or currently has pneumonitis.
  • Requires intermittent or chronic use of systemic (oral or IV) antivirals with known antiherpetic activity (eg, acyclovir).
  • Has received a live vaccine within 28 days prior to the first dose of study treatment. Note: Seasonal influenza vaccines for injection or SARS-CoV-2 are generally inactivated vaccines and are allowed (See Section6.11.2for additional guidance). Live/attenuated vaccines (such as the intranasal influenza vaccines) are not allowed.
  • Is currently participating in or has participated in a study of an investigational agent within 4 weeks prior to the first dose of study treatment.
  • Note: Patients who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks or 5 half-lives of the agent, whichever is longer, after the last dose of the previous investigational agent.
  • Conditions requiring treatment with immunosuppressive medications within 30 days. Inhaled or topical steroids, and adrenal replacement steroid dose are permitted in the absence of active autoimmune disease.
  • Note: Patients who require a brief course (≤7 days) of corticosteroids (eg, as prophylaxis for imaging studies due to hypersensitivity to contrast agents) are not excluded. Physiologic replacement doses of systemic corticosteroids are permitted, only if the dose does not exceed 10 mg/day prednisone equivalent.
  • Conditions in which anticoagulant therapies cannot be safely stopped in the periprocedural period or patients on coumadin with a target INR >2.5 or that cannot be temporarily reversed to INR ≤1.7.
  • Treatment with botanical preparations (eg, herbal supplements or traditional Chinese medicines) intended for general health support or to treat the disease under study within 2 weeks prior to treatment.
  • Prior organ transplantation including allogenic stem-cell transplantation.
  • Bowel obstruction, Major surgery ≤28 days prior to starting bevacizumab or anticipated major surgery while on study.
  • Note: If a patient received major surgery, they must have recovered adequately prior to starting study treatment and must have adequate wound healing, based on Investigator's assessment or surgeon's assessment, before starting bevacizumab.
  • History of life-threatening toxicity related to prior immune therapy (eg, anti-CTLA-4 or anti-PD-1/PD-L1 treatment or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways [eg, CD40, 4-1BB]) except those that are unlikely to recur or are expected to be manageable with standard countermeasures (eg, hormone replacement after adrenal crisis). Individual cases should be discussed with a Medical Monitor if needed.
  • Presence of peritoneal disease, or lesions that are > 5 cm or liver tumors that are estimated to invade more than one-third of the liver.
  • Prior chemoembolization, radioembolization, or other locoregional liver-directed procedures to the lesion(s)selected for intratumoral injection.

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • USC Norris Comprehensive Cancer Center

    Los Angeles, California, 90033

  • University of Washington Seattle Cancer Care Alliance

    Seattle, Washington, 98109

Other trials in United States

About this study

Official title: A Phase 2 Clinical Trial Investigating Oncolytic Immunotherapy in Combination With Atezolizumab and Bevacizumab for the Treatment of Patients With Advanced Microsatellite Stable and Mismatch Repair Proficient Colorectal Carcinoma

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.

Read the detailed description

RP2 and RP3 are selectively replication competent herpes simplex viruses 1 (HSV-1) that express exogenous genes (RP2: GM-CSF, GALV, and anti-CTLA-4; RP3: GALV, and anti-CTLA-4 hCD40L, and h4-1BBL) intended for direct injection into suitable nonneurological solid tumors. They are genetically engineered to provide direct oncolytic tumor destruction combined with the induction of a systemic antitumor immune response.

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 therapy (atezolizumab) and anti-VEGF therapy (bevacizumab) in patients with advanced MSS and pMMR CRC.

Being tested
RP2, RP3, atezolizumab, bevacizumab
Keywords
Colorectal Carcinoma, Immunotherapy, Immuno-oncology, Oncolytic virus, Oncolytic immuno-gene therapy
Medical subject headings
Colorectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RP2Biological

    Genetically modified herpes simplex type 1 virus

  • RP3Biological

    Genetically modified herpes simplex type 1 virus

  • atezolizumabBiological

    anti-PD-L1 monoclonal antibody

  • bevacizumabBiological

    anti-VEGF therapy

Study groups in NCT05733611
Study groupRoleWhat they receive
RP2 and atezolizumab plus bevacizumab in advanced MSS and pMMR CRCExperimentalRP2 will be injected by direct (including via colonoscope) or image-guided injection into injectable tumors (including subcutaneous, visceral, and nodal tumors).
Receives: Biological: RP2; Biological: atezolizumab; Biological: bevacizumab
RP3 and atezolizumab plus bevacizumab in advanced MSS and pMMR CRCExperimentalRP3 will be injected by direct (including via colonoscope) or image-guided injection into injectable tumors (including subcutaneous, visceral, and nodal tumors).
Receives: Biological: RP3; Biological: atezolizumab; Biological: bevacizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Objective Response Rate (ORR)

    Percentage of subjects achieving objective response (complete response + partial response).

    Measured: From Day 1 to documented progression of disease (up to 3 years)

Secondary outcomes (6)

  1. Frequency, Nature, and Severity of TEAEs and SAEs

    Percentage of subjects with TEAEs and SAEs

    Measured: From Screening through 60 days after last dose of RP2/RP3, or 135 days after last dose of atezolizumab/bevacizumab

  2. Overall Survival

    Overall survival is defined as the time from the first day of study treatment to the date of death by any cause

    Measured: From Day 1 to date of death by any cause (up to 3 years)

  3. Progression-free Survival

    Progression-free survival is defined as the time from the first day of study treatment to the date of progression of disease, which was subsequently confirmed, or death by any cause, whichever occurs first

    Measured: From Day 1 to documented progression of disease (up to 3 years)

  4. Duration of Response

    Duration of response is defined as the time from documented response until the date of progression of disease, which was subsequently confirmed or with no further follow-up, or death due to any cause, whichever occurs first

    Measured: From documented response to documented progression of disease (up to 3 years)

  5. Duration of Clinical Benefit

    Duration of clinical benefit is defined as the time from the first day of study treatment to last progression of disease, which was subsequently confirmed or with no further follow-up for response, or death due to any cause, whichever occurs first, for subjects who achieve complete response, partial response, or stable disease

    Measured: From Day 1 to loss of clinical benefit (up to 3 years)

  6. Complete Response Rate

    Percentage of subjects achieving a complete response

    Measured: From Day 1 to documented progression of disease (up to 3 years)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Feb 2023
  2. Study start29 Jun 2023
  3. Primary completion18 Aug 2025
  4. Study completion18 Aug 2025

Why it stopped: Business reasons.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
5 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05733611
Sponsor's protocol ID
RPL-004
Status last verified
Jan 2026
First submitted
8 Feb 2023
Last updated
2 Feb 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing RP2, RP3 and atezolizumab in people with Refractory Metastatic Colorectal Cancer and pMMR, run by Replimune, Inc. at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 22 inclusion and 34 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 2 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Business reasons.). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective Response Rate (ORR) (time frame: From Day 1 to documented progression of disease (up to 3 years)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05733611.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Feb 2026.

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