Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Respiratory Tract (Lung and Bronchial) Diseases

Rare Diseases

Breast Neoplasms

Lung Neoplasms

Melanoma

Intraocular Melanoma

All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Nivolumab

Immunoglobulins

Antibodies, Blocking

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Dose escalation of RP2 alone in 3 cohorts with IT injections in superficial tumors.

Dose escalation of RP2 alone in 3 cohorts with imaging guided IT injections in deep/visceral tumors.

Doses of RP2 (IT) in superficial tumors with nivolumab (IV).

Imaging guided doses of RP2 (IT) in deep/visceral tumors.

Doses of RP2 (IT) in HSV seronegative participants.

Genetically modified herpes simplex type 1 virus for tumor lysis and immune stimulation

Programmed death receptor (PD-1) blocking antibody

nivolumab

Clinical Trials at Replimune

Elena Garralda

Maria De Miguel

Joseph Sacco

Kevin Harrington

Mark Middleton

Kevin Harrington, MD

David Cohan, MD

RP2-001-18 is a Phase 1, multicenter, open label, single agent dose escalation and combination treatment study of RP2 in adult subjects with advanced solid tumors, to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D), as well as to evaluate preliminary efficacy.

RP2 is a genetically modified herpes simplex type 1 virus (HSV-1) that expresses an anti-CTLA-4 antibody and is designed to directly destroy tumors and to generate an anti-tumor immune response. This is a Phase 1, multicenter, open label, dose escalation and expansion, first-in-human (FIH) clinical study to evaluate the safety and tolerability, biodistribution, shedding, and preliminary efficacy of RP2 alone and in combination with nivolumab in adult subjects with advanced solid tumors.

The study will be conducted in two parts. The first part of the study is an open-label, dose escalation FIH Phase 1 study to assess the safety and tolerability of RP2 and to determine the recommended Phase 2 dose (RP2D) to be used in the second part of the study. The second part of the study is an open label design to further investigate safety of RP2 in combination with nivolumab. It will also assess the biological activity of multiple doses of RP2 in combination with nivolumab. An expansion to the second part of the study will include enrolment of a further 30 patients on RP2 in combination with nivolumab.

Following completion of the expansion in part 2, part 3 will enroll a further 15 patients on RP3 monotherapy.

The expansion to part 2 and part 3 will focus on patients with advanced or metastatic uveal melanoma, lung cancer, breast cancer or GI cancers and patients with liver metastasis.

Part 1 - Dose Escalation - Patients will be enrolled into three sequential dose level cohorts.

Part 2 - Dose expansion - Patients will receive a fixed dose of RP2 in combination with Nivolumab.

Part 3 - Patients will receive four doses of RP2 monotherapy

Study of RP2 Monotherapy and RP2 in Combination With Nivolumab in Patients With Solid Tumors

An Open-Label, Multicenter, Phase 1 Study of RP2 as a Single Agent and in Combination With PD1 Blockade in Patients With Solid Tumors

Percentage of subjects with TEAEs ≥ Grade 3

Percentage of subjects experiencing events requiring withdrawal from treatment.

MTD on the safety and response data collected during the dose escalation phase (Part 1).

RP2D of RP2 based on the safety and response data collected during the dose escalation phase (Part 1).

Percentage of subjects with biological activity determined by tumor biopsies and biomarker data

Data gathered from blood, urine, swabs of injection site, dressings, and oral mucosa to determine the shedding and biodistribution of RP2.

Change in HSV-1 antibody levels during treatment compared to baseline

Median duration of progression-free survival of subjects

Replimune Inc.

Infections

Digestive System Diseases

Carcinoma

Virus Diseases

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Retinitis Pigmentosa 15

Bevacizumab

Atezolizumab

Antibodies, Monoclonal

Immunomodulating Agents

Angiogenesis Inhibitors

Growth Inhibitors

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

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

Genetically modified herpes simplex type 1 virus

atezolizumab

bevacizumab

May Cho, MD

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.

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.

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

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

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

Percentage of subjects with TEAEs and SAEs

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

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

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

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

Percentage of subjects achieving a complete response

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Study of RP2 Monotherapy and RP2 in Combination With Nivolumab in Patients With Solid Tumors	NCT04336241	Cancer	RP2 nivolumab	18 Years -	Replimune Inc.
RP2/RP3 in Combination With Atezolizumab and Bevacizumab for the Treatment of Patients With CRC	NCT05733611	Refractory Meta... pMMR MSS	RP2 RP3 atezolizumab bevacizumab	18 Years -	Replimune Inc.

Spots Global Cancer Trial Database for rp2

Every month we try and update this database with for rp2 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for rp2

Every month we try and update this database with for rp2 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for rp2 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.