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
Overview
- Phase
- Phase 2
- Intervention
- RP2
- Conditions
- Refractory Metastatic Colorectal Cancer
- Sponsor
- Replimune Inc.
- Enrollment
- 5
- Locations
- 2
- Primary Endpoint
- Objective Response Rate (ORR)
- Status
- Terminated
- Last Updated
- 2 months ago
Overview
Brief 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.
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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.
- •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
Exclusion Criteria
- •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.
- •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
Arms & Interventions
RP2 and atezolizumab plus bevacizumab in advanced MSS and pMMR CRC
RP2 will be injected by direct (including via colonoscope) or image-guided injection into injectable tumors (including subcutaneous, visceral, and nodal tumors).
Intervention: RP2
RP2 and atezolizumab plus bevacizumab in advanced MSS and pMMR CRC
RP2 will be injected by direct (including via colonoscope) or image-guided injection into injectable tumors (including subcutaneous, visceral, and nodal tumors).
Intervention: atezolizumab
RP2 and atezolizumab plus bevacizumab in advanced MSS and pMMR CRC
RP2 will be injected by direct (including via colonoscope) or image-guided injection into injectable tumors (including subcutaneous, visceral, and nodal tumors).
Intervention: bevacizumab
RP3 and atezolizumab plus bevacizumab in advanced MSS and pMMR CRC
RP3 will be injected by direct (including via colonoscope) or image-guided injection into injectable tumors (including subcutaneous, visceral, and nodal tumors).
Intervention: RP3
RP3 and atezolizumab plus bevacizumab in advanced MSS and pMMR CRC
RP3 will be injected by direct (including via colonoscope) or image-guided injection into injectable tumors (including subcutaneous, visceral, and nodal tumors).
Intervention: atezolizumab
RP3 and atezolizumab plus bevacizumab in advanced MSS and pMMR CRC
RP3 will be injected by direct (including via colonoscope) or image-guided injection into injectable tumors (including subcutaneous, visceral, and nodal tumors).
Intervention: bevacizumab
Outcomes
Primary Outcomes
Objective Response Rate (ORR)
Time Frame: From Day 1 to documented progression of disease (up to 3 years)
Percentage of subjects achieving objective response (complete response + partial response).
Secondary Outcomes
- Frequency, Nature, and Severity of TEAEs and SAEs(From Screening through 60 days after last dose of RP2/RP3, or 135 days after last dose of atezolizumab/bevacizumab)
- Overall Survival(From Day 1 to date of death by any cause (up to 3 years))
- Duration of Response(From documented response to documented progression of disease (up to 3 years))
- Duration of Clinical Benefit(From Day 1 to loss of clinical benefit (up to 3 years))
- Progression-free Survival(From Day 1 to documented progression of disease (up to 3 years))
- Complete Response Rate(From Day 1 to documented progression of disease (up to 3 years))