Advanced Solid TumorPhase 1NCT04735978
Study of RP3 Monotherapy and RP3 in Combination With Nivolumab in Patients With Solid Tumours
A Phase 1 study testing RP3 and Nivolumab in people with Advanced Solid Tumor, run by Replimune, Inc. at 13 sites in 5 countries.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Solid Tumor
- What is being tested?
- RP3 and Nivolumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 123 participants
- Where
- 13 sitesin 5 countries
- Study dates
- 29 Dec 2020to 30 Nov 2026
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
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
- Patients with advanced or metastatic non-neurological solid tumors, who have progressed on standard therapy or cannot tolerate standard therapy, or for whom there is no standard therapy preferred to enrollment in a clinical study
- All patients must consent to provide archival tumor biopsy samples within 12 months, or a fresh tumor biopsy is needed. Patients must also consent to provide on treatment biopsies as per protocol
- At least one measurable tumor ≥ 1 cm in longest diameter (or shortest diameter for lymph nodes)
- At least one injectable tumor ≥ 1 cm in longest diameter or injectable tumors which in aggregate are ≥ 1 cm in longest diameter (or shortest diameter for lymph nodes
- Have an Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- Note: Predefined inclusion criteria may apply for each additional expansion cohort.
Who cannot join
- Prior treatment with an oncolytic virus therapy
- History of viral infections according to the protocol
- Systemic infection requiring intravenous (IV) antibiotics
- Active significant herpetic infections or prior complications of HSV-1 infection (e.g., herpetic keratitis or encephalitis)
- Requires intermittent or chronic use of systemic antivirals
- Hepatocellular carcinoma patients with a diagnosis of hepatitis B must be off antiviral therapy for at least 4 weeks prior to enrollment . Hepatocellular carcinoma patients with a history of or ongoing hepatitis C infection must have completed treatment for hepatitis C at least 1 month prior to study enrollment and hepatitis
Show all 20Show fewer
- History of interstitial lung disease
- Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis
- Additional Exclusion Criteria for Patients Enrolled in Part 2 (Expansion Cohorts):
- History of life-threatening toxicity related to prior immune treatment or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways
- Treatment with botanical preparations within 2 weeks prior to treatment.
- Active, known, or suspected autoimmune disease requiring systemic treatment.
- History of interstitial lung disease.
- Severe hypersensitivity to another monoclonal antibody.
- Has received prior radiotherapy within 2 weeks of start of study treatment.
- Has received a live vaccine within 28 days prior to the first dose of study treatment.
- History of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
- History of myocarditis or congestive heart failure within 6 months of screening.
- Has a serious or uncontrolled medical disorder.
- Has a QT interval corrected for heart rate using Fridericia's formula (QTcF) > 480 msec, except for right bundle branch block.
Trial locations and contacts
13 sites in 5 countries.
13 sites in 5 countries
Spain4 sites
Vall d'Hebron Hospital Hospital Universitario Vall d´Hebron (Vall d'Hebron University Hospital)
Barcelona, 08035
Hospital Clinic Barcelona
Barcelona, 08036
START Madrid CIO Clara Campal, Hospital Universitario HM Sanchinarro Unidad de Ensayos Fase I Panta 3
Madrid, 28050
Hospital Clinico Universitario de Valencia
Valencia, 46010
United States3 sites
MD Anderson Cancer Center
Houston, Texas, 77030
University of Iowa
Iowa City, Iowa, 52242
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232
United Kingdom3 sites
The Clatterbridge Cancer Centre NHS Foundation Trust
Bebington, Merseyside, CH63 4JY
The Royal Marsden NHS Foundation Trust
London, SW3 6JJ
Churchill Hospital
Oxford, OX3 9DU
Greece2 sites
University of Athens
Athens, 11527
University General Hospital Attikon
Athens, 12462
France1 site
Laboratoire de Recherche Translationnelle en Immunotherapie (LRTI), Gustave Roussy
Villejuif, 94805
About this study
Official title: 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
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.
Read the detailed description
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
- Conditions
- Advanced Solid Tumor
- Being tested
- RP3, Nivolumab
- Keywords
- Advanced solid tumors, Immunotherapy, Immuno-oncology, Oncolytic virus, Oncolytic immuno-gene therapy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RP3Biological
Genetically modified HSV-1
NivolumabBiological
anti-PD1 monoclonal antibody
| Study group | Role | What they receive |
|---|---|---|
| Dose escalation of RP3 - superficial and/or deep/visceral tumors | Experimental | Dose escalation of RP3 alone in 2 cohorts with intratumoral (IT) injections including use of imaging guided injection for deep tumors. Receives: Biological: RP3 |
| Dose combination of RP3 and anti-PD1 therapy - superficial and/or deep/visceral tumors | Experimental | Dose combination of RP3 and anti-PD1 therapy. IT injections of RP3 including use of imaging guided injection for deep tumors. Receives: Biological: RP3; Biological: Nivolumab |
| Seronegative cohort | Experimental | Doses of RP3 (IT) in HSV seronegative participants. Receives: Biological: RP3 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of dose limiting toxicities (DLTs) during the DLT period
Percentage of participants with DLTs
Measured: From Day 1 up to 30 days after last dose
Incidence and severity of treatment emergent adverse events (TEAEs)
Percentage of participants with TEAEs
Measured: From Day 1 up to 60 days after last dose
Incidence and severity of serious adverse events (SAEs)
Percentage of participants with SAEs
Measured: From Day 1 up to 60 days after last dose
Incidence of TEAEs ≥ Grade 3
Percentage of participants with TEAEs ≥ Grade 3
Measured: From Day 1 up to 60 days after last dose
Percentage of events requiring withdrawal
Percentage of participants experiencing events requiring withdrawal from treatment.
Measured: From Day 1 up to last dose (up to 8 weeks in escalation phase and up to 2 years in combination phase)
Recommended phase 2 dose (RP2D) of RP3
RP2D of RP3 based on the safety and response data collected during the dose escalation phase (Part 1)
Measured: 7 months
Secondary outcomes (12)
Percentage of biologic activity
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).
Measured: From Day 1 to 24 months following the last dose in dose escalation. From Day 1 to 100 days following the last dose in dose combination
Incidence of clearance of RP3 from blood and urine
Incidence of clearance of RP3 from blood and urine before and after each injection
Measured: From Day 1 to 60 days following the last dose in dose escalation. From Day 1 to 100 days following the last dose in dose combination
Percentage of participants with detectable RP3.
Data gathered from blood, urine, swabs of injection site, dressing and oral mucosa to determine the shedding and biodistribution of RP3
Measured: From Day 1 to 60 days following the last dose in dose escalation. From Day 1 to 100 days following the last dose in dose combination
Change in HSV-1 antibody levels
Change in HSV-1 antibody levels during treatment compared to baseline
Measured: From Day 1 to Day 43
Percentage of HSV-1 seronegative patients with TEAEs
Percentage of HSV-1 seronegative patients with TEAEs
Measured: From Day 1 to 60 days following last dose in dose escalation. From Day 1 to 100 days post last dose in dose combination
Percentage of objective overall response rate (ORR)
Percentage of ORR
Measured: Up to 3 years since first patient in
Median duration of response
Median duration of response of participants
Measured: Up to 3 years since first patient in
Percentage of complete response (CR)
Percentage of participants with a CR
Measured: From Day 1 up to last dose (Day 57 or 8th Re-initiation dose in escalation phase and up to 2 years for combination phase)
Percentage of partial response (PR)
Percentage of participants with a PR
Measured: From Day 1 up to last dose (Day 57 or 8th Re-initiation dose in escalation phase and up to 2 years for combination phase)
Percentage of stable disease (SD)
Percentage of participants with SD
Measured: From Day 1 up to last dose (Day 57 or 8th Re-initiation dose in escalation phase and up to 2 years for combination phase)
Progression-free survival by Investigator review
Length of time during and after treatment, that a patient lives with disease but it does not get worse
Measured: From Day 1 to day of last follow-up
One-year and 2-year OS rates
Percentage of participants from Day 1 of treatment who reach one year or two year survival
Measured: From Day 1 to Day 730
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Feb 2021
- Study start29 Dec 2020
- Primary completion30 Nov 2026 (estimated)
- Study completion30 Nov 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Solid TumorStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- 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)
- Masking
- None (open label)
- Enrolment
- 123 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Replimune, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Bristol-Myers Squibb
- Responsible party
- Sponsor
- Investigators
- Gary Vanasse, MD, Study director, Replimune, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04735978
- Sponsor's protocol ID
- RP3-301
- Status last verified
- Feb 2026
- First submitted
- 25 Jan 2021
- Last updated
- 27 Feb 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT04735978
- Acronym / sponsor ID
- RP3-301
- Conditions
- Advanced Solid Tumor
- Keywords
- Advanced solid tumors, Immunotherapy, Immuno-oncology, Oncolytic virus, Oncolytic immuno-gene therapy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 123 participants (estimated)
- Lead sponsor
- Replimune, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Bristol-Myers Squibb
- Study start
- 29 Dec 2020 (actual)
- Primary completion
- 30 Nov 2026 (estimated)
- Study completion
- 30 Nov 2026 (estimated)
- First posted
- 3 Feb 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- 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)
| Arm | Type | Receives |
|---|---|---|
| Dose escalation of RP3 - superficial and/or deep/visceral tumors | Experimental | Biological: RP3Dose 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 - superficial and/or deep/visceral tumors | Experimental | Biological: RP3, Biological: NivolumabDose combination of RP3 and anti-PD1 therapy. IT injections of RP3 including use of imaging guided injection for deep tumors. |
| Seronegative cohort | Experimental | Biological: RP3Doses of RP3 (IT) in HSV seronegative participants. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Patients with advanced or metastatic non-neurological solid tumors, who have progressed on standard therapy or cannot tolerate standard therapy, or for whom there is no standard therapy preferred to enrollment in a clinical study
- All patients must consent to provide archival tumor biopsy samples within 12 months, or a fresh tumor biopsy is needed. Patients must also consent to provide on treatment biopsies as per protocol
- At least one measurable tumor ≥ 1 cm in longest diameter (or shortest diameter for lymph nodes)
- At least one injectable tumor ≥ 1 cm in longest diameter or injectable tumors which in aggregate are ≥ 1 cm in longest diameter (or shortest diameter for lymph nodes
- Have an Eastern Cooperative Oncology Group (ECOG) performance status 0-1
Key exclusion criteria (20 listed)
- Prior treatment with an oncolytic virus therapy
- History of viral infections according to the protocol
- Systemic infection requiring intravenous (IV) antibiotics
- Active significant herpetic infections or prior complications of HSV-1 infection (e.g., herpetic keratitis or encephalitis)
- Requires intermittent or chronic use of systemic antivirals
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RP3Genetically modified HSV-1 | Biological | Dose combination of RP3 and anti-PD1 therapy - superficial and/or deep/visceral tumors, Dose escalation of RP3 - superficial and/or deep/visceral tumors, Seronegative cohort |
| Nivolumabanti-PD1 monoclonal antibody | Biological | Dose combination of RP3 and anti-PD1 therapy - superficial and/or deep/visceral tumors |
Primary outcome
Incidence of dose limiting toxicities (DLTs) during the DLT period
Time frame: From Day 1 up to 30 days after last dose
Percentage of participants with DLTs
Incidence and severity of treatment emergent adverse events (TEAEs)
Time frame: From Day 1 up to 60 days after last dose
Percentage of participants with TEAEs
Incidence and severity of serious adverse events (SAEs)
Time frame: From Day 1 up to 60 days after last dose
Percentage of participants with SAEs
Incidence of TEAEs ≥ Grade 3
Time frame: From Day 1 up to 60 days after last dose
Percentage of participants with TEAEs ≥ Grade 3
Percentage of events requiring withdrawal
Time frame: From Day 1 up to last dose (up to 8 weeks in escalation phase and up to 2 years in combination phase)
Percentage of participants experiencing events requiring withdrawal from treatment.
Recommended phase 2 dose (RP2D) of RP3
Time frame: 7 months
RP2D of RP3 based on the safety and response data collected during the dose escalation phase (Part 1)
12 secondary outcomes
Percentage of biologic activity
Time frame: From Day 1 to 24 months following the last dose in dose escalation. From Day 1 to 100 days following the last dose in dose combination
Incidence of clearance of RP3 from blood and urine
Time frame: From Day 1 to 60 days following the last dose in dose escalation. From Day 1 to 100 days following the last dose in dose combination
Percentage of participants with detectable RP3.
Time frame: From Day 1 to 60 days following the last dose in dose escalation. From Day 1 to 100 days following the last dose in dose combination
Change in HSV-1 antibody levels
Time frame: From Day 1 to Day 43
Percentage of HSV-1 seronegative patients with TEAEs
Time frame: From Day 1 to 60 days following last dose in dose escalation. From Day 1 to 100 days post last dose in dose combination
Percentage of objective overall response rate (ORR)
Time frame: Up to 3 years since first patient in
Median duration of response
Time frame: Up to 3 years since first patient in
Percentage of complete response (CR)
Time frame: From Day 1 up to last dose (Day 57 or 8th Re-initiation dose in escalation phase and up to 2 years for combination phase)
Percentage of partial response (PR)
Time frame: From Day 1 up to last dose (Day 57 or 8th Re-initiation dose in escalation phase and up to 2 years for combination phase)
Percentage of stable disease (SD)
Time frame: From Day 1 up to last dose (Day 57 or 8th Re-initiation dose in escalation phase and up to 2 years for combination phase)
Progression-free survival by Investigator review
Time frame: From Day 1 to day of last follow-up
One-year and 2-year OS rates
Time frame: From Day 1 to Day 730
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Feb 2026.
Related trials for Advanced Solid Tumor
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
Active, not recruitingPhase 1
A Study to Assess Safety, Tolerability, and Pharmacokinetics of ABSK043 in Patients With Advanced Solid Tumor
Neoplasms
RecruitingPhase 1/2
A Study of Neladalkib (NVL-655) in Patients With Advanced NSCLC and Other Solid Tumors Harboring ALK Rearrangement or Activating ALK Mutation (ALKOVE-1)
Locally Advanced Solid Tumor, Metastatic Solid Tumor
Active, not recruitingPhase 2
Testing AZD5363 as a Potential Targeted Treatment in Cancers With AKT Genetic Changes (MATCH-Subprotocol Y)
Advanced Lymphoma, Advanced Malignant Solid Neoplasm
RecruitingPhase 1/2
Docetaxel and SX-682 in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma, Salivary Gland Carcinoma, and Advanced Prostate Cancer
Head and Neck Cancer, Head and Neck Squamous Cell Carcinoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gary Vanasse, MD study director
Replimune, Inc.
13 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing RP3 and Nivolumab in people with Advanced Solid Tumor, run by Replimune, Inc. at 13 sites in 5 countries.
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 6 inclusion and 20 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: under way, not looking for participants, as of the sponsor's last update on 27 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 13 sites in Spain, United States, United Kingdom, Greece, France. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
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?
Incidence of dose limiting toxicities (DLTs) during the DLT period (time frame: From Day 1 up to 30 days after last dose). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 27 Feb 2026.