Neoplasms

All Conditions

Infections

Digestive System Diseases

Rare Diseases

Carcinoma

Virus Diseases

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Retinitis Pigmentosa 15

Antineoplastic Agents

All Drugs and Chemicals

Bevacizumab

Atezolizumab

Antibodies

Antibodies, Monoclonal

Immunomodulating Agents

Immunoglobulins

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

Immune Checkpoint 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

Roche Pharma AG

Replimune Inc.

Symptoms and General Pathology

Recurrence

Carcinoma, Squamous Cell

Squamous Cell Carcinoma of Head and Neck

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Disease Attributes

Neoplasms, Squamous Cell

Head and Neck Neoplasms

Nivolumab

Paclitaxel

Albumin-Bound Paclitaxel

Carboplatin

Cisplatin

Tubulin Modulators

Antimitotic Agents

RP3 will be administered via direct intratumoral injection or via CT, ultrasound, or laryngoscopy guided intratumoral injection into superficial, subcutaneous (SC), or nodal lesions and into deeper lesions, including visceral lesions.

standard-of-care CCRT (defined as intensity-modulated radiation therapy \[IMRT\] and cisplatin

CCRT consisting of intensity modulated radiation therapy combined with a cis-platinum

CCRT(concurrent chemoradiation therapy)

carboplatin and paclitaxel

nivolumab

David Cohan, MD/FACS

This is a Phase 2, multicenter, open-label, 2-cohort (Locoregionally Advanced Cohort or Recurrent/Metastatic Cohort) study evaluating RP3 in combination with concurrent chemoradiation therapy (CCRT) followed by nivolumab (for the LA Cohort) or combined with chemotherapy and nivolumab (for the R/M Cohort) in patients with advanced, inoperable squamous cell carcinomas of the head and neck (SCCHN), including of the oral cavity, oropharynx, hypopharynx, larynx, or unknown primary.

RP3 is a genetically modified herpes simplex type 1 virus (HSV-1) that expresses exogenous genes (anti-CTLA-4 antibody, CD40 ligand and h4-1BBL) designed to directly kill tumor cells and generate a systemic anti-tumor immune response

Study of RP3 in Combination With Nivolumab and Other Therapy in Patients With Locoregionally Advanced or Recurrent SCCHN

A Phase 2, Open-label, Multicenter Study Investigating Oncolytic Immunotherapy in Combination With Other Therapy in Patients With Locoregionally Advanced or Recurrent Squamous Cell Carcinoma of the Head and Neck

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

Overall Response Rate is the percentage of subjects achieving objective response (complete response + partial response) Metabolic overall response rate is the percentage of subjects achieving objective metabolic response (complete metabolic response + partial metabolic response)

Complete response rate is the percentage of subjects achieving complete response

Metabolic complete response rate is the percentage of subjects achieving metabolic complete response

No-evidence-of-disease is defined as no evidence of malignancy at any site

Locoregional Failure is defined as tumor growth or disease infiltration or spread at the primary tumor location and/or at anatomic areas of local and/or regional disease.

Distant metastatic failure is defined as growth of metastases or new appearance of metastases in lung, bone, liver, other distant organs, and/or distant lymph node stations.

FACT-HNSI-22 is a Functional Assessment of Cancer Therapy Head \& Neck Cancer Symptom Index which consists of 22 items. Each item is scored in a 5 point Likert-type scale: 0=Not at all, 1=A little bit, 2=Some-what, 3=Quite a bit, and 4=Very much. The higher the score, the worse the patient outcome.

EQ-5D-5L is a self-assessed, health related, quality of life questionnaire which consists of 2 pages: EQ-5D descriptive system and EQ visual analogue scale (EQ VAS). The EQ-5D descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The EQ VAS records the patient's self-rated health on a vertical visual analogue scale which is numbered from 0 to 100. 0 means the worst health the patient can imagine. 100 means the best health the patient can imagine. The higher the score, the better the patient outcome.

Percentage of patients achieving complete response, partial response, or stable disease

Number of Patients Who Undergo Attempted Definitive Resection

Bristol-Myers Squibb

Carcinoma, Hepatocellular

Adenocarcinoma

Liver Neoplasms

Liver Diseases

RP3 will be injected by direct or image-guided injection into injectable tumors (eg,primary sitehepatic tumors, hepatic metastases, non-hepatic metastases, visceral, or nodal tumors).

Clinical Trials at Replimune

Adam Burgoyne, MD

Asad Javed

Kevin Kim

Renuka Iyer

Davendra Sohal, MD

Thomas Karasic, MD

Anwaar Saeed

Axel Grothey, MD

Gentry King, MD

Mohamed Bouattour

Julien Peron

Jean-Frederic Blanc

Julien Edeline

Olivier Rosmorduc

Cristina Smolenschi, MD

Thorsten Goetze

Florian van Bömmels

Peter Galle

Ioannis Koskinas

Ioannis Souglakos

Adel Samson

Daniel Palmer

Debashis Sarker

Mark Middleton

Jaroslaw Jac, MD

This is a Phase 2, open-label, 2-cohort clinical study evaluating RP3 in combination with atezolizumab plus bevacizumab as First- or Second-line Systemic Therapy in patients with locoregionally advanced and/or metastatic Hepatocellular Carcinoma not amenable to surgical resection or standard locoregionally directed therapies.

RP3 in Combination With 1L or 2L Therapy in Patients With Locally Advanced Unresectable or Metastatic HCC

A Phase 2, Open-label, Multicenter Study Investigating RP3 Oncolytic Immunotherapy in Combination With First- or Second-line Therapy in Patients With Locally Advanced Unresectable or Metastatic Hepatocellular Carcinoma

Percentage of subjects with objective response (complete response + partial response) per RECIST modified for use in the HCC setting

Percentage of subjects achieving complete response

Percentage of subjects achieving complete response, partial response, or stable disease

Dose escalation of RP3 alone in 2 cohorts with intratumoral (IT) injections including use of imaging guided injection for deep tumors.

Dose combination of RP3 and anti-PD1 therapy. IT injections of RP3 including use of imaging guided injection for deep tumors.

Doses of RP3 (IT) in HSV seronegative participants.

David Cohan, MD

This is a Phase 1, multicenter, open label, single agent dose escalation and combination treatment study of RP3 in adult participants with advanced solid tumors, to evaluate the safety and tolerability of RP3 both as a single agent and in combination with anti-PD1 therapy and to determine the recommended Phase 2 dose (RP2D) of RP3.

RP3 is a genetically modified herpes simplex type 1 virus (HSV-1) that expresses exogenous genes (anti-CTLA-4 antibody, CD40 ligand and h4-1BBL) designed to directly destroy tumors and generate an anti-tumor immune response

Part 1 - Dose Escalation - Participants will be enrolled into two sequential dose level cohorts.

* Cohort 1: 1 × 105 plaque-forming units (PFU)/mL on Day 1 followed by 1 × 106 PFU/mL every 2 weeks (Q2W) for up to 5 doses.
* Cohort 2: 1 × 106 PFU/mL on Day 1 followed by 1 × 107 PFU/mL Q2W for up to 5 doses.

Part 2 - Dose Combination - Patients will be enrolled into 1 of 5 dose-expansion cohorts. Expansion Cohorts 1, 2, and 4 will enroll patients with head and neck cancer, lung cancer, breast cancer, or GI cancer. Expansion Cohort 3 will enroll patients with any solid organ malignancy who have at least 2 tumors that can be injected and biopsied. Expansion Cohort 5 will enroll patients with melanoma.

* Expansion Cohort 1 (RP3 + Nivolumab)
* Expansion Cohort 2 (RP3 Followed by Nivolumab)
* Expansion Cohort 3 (RP3 Monotherapy Translational Cohort)
* Expansion Cohort 4 (RP3 Monotherapy)
* Expansion Cohort 5 (RP3 + Nivolumab in Melanoma)

Study of RP3 Monotherapy and RP3 in Combination With Nivolumab in Patients With Solid Tumours

An Open-Label, Multicenter, Phase 1 Study of RP3 as a Single Agent and in Combination With PD-1 Blockade in Patients With Solid Tumors

Percentage of participants with TEAEs ≥ Grade 3

Percentage of participants experiencing events requiring withdrawal from treatment.

RP2D of RP3 based on the safety and response data collected during the dose escalation phase (Part 1)

Percentage of participants with biological activity as assessed by individual tumor responses (including erythema, necrosis, and/or inflammation and changes in tumor sizes, in injected and uninjected tumors).

Incidence of clearance of RP3 from blood and urine before and after each injection

Data gathered from blood, urine, swabs of injection site, dressing and oral mucosa to determine the shedding and biodistribution of RP3

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

Percentage of HSV-1 seronegative patients with TEAEs

Median duration of response of participants

Length of time during and after treatment, that a patient lives with disease but it does not get worse

Percentage of participants from Day 1 of treatment who reach one year or two year survival

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
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.
Study of RP3 in Combination With Nivolumab and Other Therapy in Patients With Locoregionally Advanced or Recurrent SCCHN	NCT05743270	Squamous Cell C... Locally Advance... Recurrent Head ...	RP3 CCRT(concurrent... carboplatin and... nivolumab	18 Years -	Replimune Inc.
RP3 in Combination With 1L or 2L Therapy in Patients With Locally Advanced Unresectable or Metastatic HCC	NCT05733598	Locally Advance... Recurrent Hepat... Metastatic Hepa...	RP3 atezolizumab bevacizumab	18 Years -	Replimune Inc.
Study of RP3 Monotherapy and RP3 in Combination With Nivolumab in Patients With Solid Tumours	NCT04735978	Advanced Solid ...	RP3 Nivolumab	18 Years -	Replimune Inc.

Spots Global Cancer Trial Database for rp3

Every month we try and update this database with for rp3 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 rp3

Every month we try and update this database with for rp3 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 rp3 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.