Ended Phase I and Phase II (Integrated)- First administration to humans Solid tumors

Study of RP1 Monotherapy and RP1 in Combination With Nivolumab (IGNYTE)

EU CTIS ID: 2024-511728-15-00

What this study is testing

Phase 1: To determine the maximum tolerated dose (MTD) as determined by incidence of dose limiting toxicities (DLTs) and/or the recommended Phase 2 dose (RP2D) of RP1 To assess the safety and tolerability of RP1 alone and in combination with nivolumab as determined by the incidence of all treatment-emergent adverse events (TEAEs), ≥ Grade 3 TEAEs, serious adverse events (SAEs), and TEAEs requiring withdrawal from investigational product (IP) treatment Phase 2: Primary: To assess the safety and tolerability of RP1 in combination with nivolumab as determined using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 (v5.0) by the incidence of all TEAEs, ≥ Grade 3 TEAEs, SAEs, and TEAEs requiring withdrawal from RP1 treatment To assess the efficacy of RP1 in combination with nivolumab as determined by ORR according to Investigator review To assess the efficacy of RP1 in combination with nivolumab in the anti-programmed cell death protein 1 (anti-PD1) failed cutaneous melanoma cohort as determined by ORR according to independent review

Phase I and Phase II (Integrated)- First administration to humans

A plain-language read of the study's public EU CTIS listing. The study team confirms the details.

Who can take part

You may be able to join if

Voluntary agreement to provide written informed consent prior to any study procedures and the willingness and ability to comply with all aspects of the protocol.
Coagulation: a. Prothrombin time (PT) or international normalization ratio (INR) ≤ 1.5 × ULN, 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 pretreatment INR < 2.5 × ULN. (Guidance for the peri-procedural management of anticoagulants is provided in Appendix E).
Patients must have an ECOG performance status (PS) ≤ 1.
Phase 1 patients only: Patients with histologically or cytologically confirmed advanced or metastatic non-neurological solid tumors, who have progressed on standard therapy or cannot tolerate standard therapy, or for which there is no standard therapy preferred to enrollment in a clinical trial. Note: There is no limit to the number of prior treatment regimens.
Phase 1 Expansion and Phase 2 patients only: Have provided either a formalin-fixed, paraffin-embedded (FFPE) tissue block or unstained tumor tissue sections, obtained within 6 months prior to enrollment, with an associated pathology report, which must be submitted to the core laboratory for inclusion. Biopsy should be excisional, incisional or core needle. Fine needle aspiration is unacceptable for submission. A fresh biopsy is required at screening if an archival biopsy (within 6 months prior to enrollment) is not available.
Phase 1 Expansion and Phase 2 patients only: Measurable disease based upon RECIST v1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.

You likely can't join if

Prior treatment with an oncolytic therapy.
Has serious or uncontrolled medical disorders
Has known psychiatric, alcohol abuse, or substance abuse disorders that would interfere with cooperating with the requirements of the study.
Female who has a positive serum pregnancy test (at screening within 72 hours before dosing) or urine pregnancy test (Cycle 1 Day1) or is breastfeeding or planning to become pregnant during study treatment or within 90 days (RP1 alone) or 150 days (RP1 and nivolumab) after the last dose of study treatment.
Has clinically significant cardiovascular disease within 12 months from first dose of study drug, including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, cerebral vascular accident, or cardiac arrhythmia associated with hemodynamic instability.
Is currently participating in or has participated in a study of an investigational agent or has used an investigational device 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 at least 4 weeks since the last dose of the previous investigational agent.

See the full eligibility criteria

Who can join

Voluntary agreement to provide written informed consent prior to any study procedures and the willingness and ability to comply with all aspects of the protocol.
Coagulation: a. Prothrombin time (PT) or international normalization ratio (INR) ≤ 1.5 × ULN, 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 pretreatment INR < 2.5 × ULN. (Guidance for the peri-procedural management of anticoagulants is provided in Appendix E).
Patients must have an ECOG performance status (PS) ≤ 1.
Phase 1 patients only: Patients with histologically or cytologically confirmed advanced or metastatic non-neurological solid tumors, who have progressed on standard therapy or cannot tolerate standard therapy, or for which there is no standard therapy preferred to enrollment in a clinical trial. Note: There is no limit to the number of prior treatment regimens.
Phase 1 Expansion and Phase 2 patients only: Have provided either a formalin-fixed, paraffin-embedded (FFPE) tissue block or unstained tumor tissue sections, obtained within 6 months prior to enrollment, with an associated pathology report, which must be submitted to the core laboratory for inclusion. Biopsy should be excisional, incisional or core needle. Fine needle aspiration is unacceptable for submission. A fresh biopsy is required at screening if an archival biopsy (within 6 months prior to enrollment) is not available.
Phase 1 Expansion and Phase 2 patients only: Measurable disease based upon RECIST v1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
Phase 1 Expansion and Phase 2 Patients only: Life expectancy of at least 3 months.
Melanoma cohort: Diagnosis of Stage IIIb-IV melanoma (ocular and mucosal allowed).
Melanoma cohort: Patients for whom PD1 directed therapy is indicated according to a current approved label or who have previously received a PD1/PD-L1 directed therapy, or have exhausted or become intolerant to, or refuse, currently available therapies for melanoma. Note: Only 1 line of prior systemic therapy for metastatic disease (combination ipilimumab/nivolumab is considered 1 line of therapy for the purposes of determining eligibility), other than adjuvant, is allowed.
Anti-PD1 failed cutaneous melanoma cohort: Diagnosis of unresectable Stage IIIb-IV cutaneous melanoma.
Anti-PD1 failed cutaneous melanoma cohort: Disease progression must have been confirmed and documented using clinical or radiological assessment by 2 assessments at least 4 weeks apart while being treated with an anti-PD1 antibody (e.g., nivolumab or pembrolizumab), administered either as monotherapy or in combination with anti-cytotoxic T-lymphocyte antigen-4 (anti–CTLA-4) (e.g., ipilimumab), targeted therapies, chemotherapy, or investigational agents (oncolytic virus [OV] therapy excluded) for at least 8 consecutive weeks.
Male or female ≥ 18 years of age on the day of signed informed consent
Anti-PD1 failed cutaneous melanoma cohort: Treatment with prior anti-PD1 therapy must have continued from the time of initial tumor progression until confirmation of progressive disease (PD) (i.e., such that no doses of anti-PD1 therapy are missed). Radiological confirmation o-f PD can occur during the screening period for this study. Note: If radiographic progression at the initial scan where progression was documented is accompanied by clear clinical progression, defined as a decline in performance status directly attributed to disease or increased disease related symptoms, anti-PD1 therapy does not need to continue.
Anti-PD1 failed cutaneous melanoma cohort:Patients must have known and documented BRAF mutation status. If BRAFV600 mutation-positive, a BRAF inhibitor alone or BRAF/MEK directed therapy (at Investigator’s discretion) is also allowed prior to anti-PD1 therapy.
Anti-PD1 failed cutaneous melanoma cohort: Patients treated with anti-PD1 in the adjuvant setting with documented disease progression while on adjuvant therapy may enroll. In this setting, a confirmatory biopsy can be used in place of a confirmatory scan. Germany-specific IC #22: Patients with known and documented BRAF mutation status should have received appropriate standard of care unless they have refused such therapy or are intolerant to such therapy.
Anti-PD1 failed cutaneous melanoma cohort: Lactate dehydrogenase (LDH) < 2.0 × ULN. Up to 20% of patients with LDH ≥ 2 × ULN may enroll provided all other eligibility criteria are met.
MSI-H or dMMR cohort: Diagnosis of metastatic MSI-H or metastatic dMMR who have progressed on prior anti-PD-1/PD-L1 therapy. France-specific IC #24: Diagnosis of metastatic MSI-H or metastatic dMMR who have progressed on prior anti-PD1 therapy and have exhausted, become intolerant to, or in the opinion of the Investigator are not candidates for any other currently available therapies for their cancer. Note: Anti-PD-1 therapy must be the immediate prior therapy.
NMSC cohort: Histologic diagnosis of locally advanced or metastatic NMSC that are not considered treatable with surgical excision; including patients with basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (CSCC), basosquamous carcinoma (BSC), Merkel cell carcinoma (MCC), high grade dermatofibrosarcoma protuberans (DFSP), angiosarcoma of the skin, non-human immunodeficiency virus (non-HIV)-related Kaposi’s sarcoma, sebaceous gland carcinoma, and eccrine carcinomas including eccrine porocarcinoma, hidradenocarcinoma, mucinous eccrine carcinoma, and microcystic adnexal carcinoma; cutaneous T-cell lymphoma (CTCL) is excluded. a. Anti-PD1/PD-L1 naïve NMSC patients: patients for whom PD1/PD-L1 directed therapy is indicated according to a current approved label or have exhausted or become intolerant to, or refuse, currently available therapies for their cancer. France-specific IC #25: Anti-PD-L1 naïve NMSC patients: patients for whom PD1/PD-L1 directed therapy is indicated according to a current approved label or have exhausted or become intolerant to currently available therapies for their cancer. b. Anti-PD1/PD-L1 failed NMSC patients: Patients must have received at least 8 weeks of anti-PD1/PD-L1 as their last line of therapy and progressed while on treatment. For CSCC, mixed histology may be allowed, provided that the major histological component is SCC, after consultation with the Medical Monitor. Note: Patients with CSCC may have received prior chemotherapy or epidermal growth factor receptor (EGFR) inhibitor therapy. Patients with NMSC and co-existing chronic
Anti-PD1/PD-L1 failed NSCLC cohort: Histologically confirmed diagnosis of squamous or non-squamous NSCLC.
Anti-PD1/PD-L1 failed NSCLC cohort: Must have failed prior treatment, including PD1/PD-L1 directed therapy administered either as monotherapy or in combination with platinum-based chemotherapy or anti-CTLA-4. The most recent treatment regimen must have included an anti-PD1/PD-L1 directed therapy with radiologic disease progression on or after treatment. Note: Patients with documented, known genomic tumor aberrations such as EGFR, ALK, ROS1, or BRAF V600E should also have received appropriate standard of care targeted therapy. France-specific IC #27: Must have failed prior standard-of-care treatment, including PD1/PD-L1 directed therapy administered either as monotherapy or in combination with platinum-based chemotherapy or anti-CTLA-4 and chemotherapy, when appropriate. The most recent treatment regimen must have included an anti-PD1/PD-L1 directed therapy with radiologic disease progression on or after treatment. Note: Patients with documented, known genomic tumor aberrations such as EGFR, ALK, ROS1, or BRAF V600E should also have received appropriate standard of care targeted therapy.
Anti-PD1/PD-L1 failed NSCLC cohort: Has measurable disease per RECIST v.1.1 with no tumor exceeding 7 cm in longest diameter. Notes: (a) A minimum of 30% of patients should have liver metastases that are suitable and intended for IT injection with RP1. (b) Patients who only exhibit disease that may be invading the heart, great vessels, or other critical structures, and no other injectable lesions, are not eligible.
At least 1 measurable tumor of ≥ 1 cm in longest diameter or ≥ 1.5 cm in shortest diameter for lymph nodes) and injectable lesions which in aggregate comprise ≥ 1 cm in longest diameter.
Females of childbearing potential must have a negative beta-human chorionic gonadotropin (β-hCG) test with a minimum sensitivity of 25 IU/L or equivalent units of β-hCG at screening within 72 hours before the first dose and a negative urine pregnancy test on Cycle 1 Day 1. For serum and urine pregnancy tests and instructions (see Section 9.6.9).
Female patients of reproductive potential must agree to avoid becoming pregnant and adhere to a highly effective contraception method until 90 days after the last dose of RP1 alone or 150 days after the last dose of RP1 and nivolumab. For a definition of highly effective contraceptive methods and instructions of patients and partners (see Section 9.6.9).
Male patients of reproductive potential must agree to avoid impregnating a partner and adhere to a highly effective contraception method until 90 days after last dose of RP1 and refrain from donating sperm during this period. For a definition of highly effective contraceptive methods and instructions of patients and partners (see Section 9.6.9).
Adequate hematologic function including: a. White blood cell count (WBC) ≥ 2.0 × 109/L b. Absolute neutrophil count (ANC) ≥ 1.5 × 109/L c. Platelet count ≥ 100 × 109/L d. Hemoglobin ≥ 9 g/dL or ≥ 5.6 mmol/L (without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within 2 weeks of dosing).
Adequate hepatic function including: a. Total bilirubin ≤ 1.5 × upper limit of normal (ULN) (except patients with Gilbert Syndrome who must have a total bilirubin of < 3.0 × ULN) or direct bilirubin ≤ ULN for a patient with total bilirubin level > 1.5 × ULN. If total bilirubin is > 1.5 × ULN but ≤ 3 × ULN, both aminotransferase (AST and ALT) levels must be ≤ 3 × ULN. b. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 × ULN (or ≤ 5.0 × ULN, if liver metastases). Note: If aminotransferase levels (AST and/or ALT) are > 3 × ULN but ≤ 5 × ULN, total bilirubin must be ≤ 1.5 × ULN. c. Alkaline phosphatase (ALP) ≤ 2.5 × ULN (or ≤ 5.0 × ULN, if liver or bone metastases).
Adequate renal function: Blood creatinine ≤ 1.5 × ULN or measured or calculated (using Cockcroft) creatinine clearance ≥ 30 mL/minute for patients with creatinine levels > 1.5 × institutional ULN.

What rules you out

Prior treatment with an oncolytic therapy.
Has serious or uncontrolled medical disorders
Has known psychiatric, alcohol abuse, or substance abuse disorders that would interfere with cooperating with the requirements of the study.
Female who has a positive serum pregnancy test (at screening within 72 hours before dosing) or urine pregnancy test (Cycle 1 Day1) or is breastfeeding or planning to become pregnant during study treatment or within 90 days (RP1 alone) or 150 days (RP1 and nivolumab) after the last dose of study treatment.
Has clinically significant cardiovascular disease within 12 months from first dose of study drug, including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, cerebral vascular accident, or cardiac arrhythmia associated with hemodynamic instability.
Is currently participating in or has participated in a study of an investigational agent or has used an investigational device 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 at least 4 weeks since the last dose of the previous investigational agent.
History of interstitial lung disease.
History of documented allergic reactions or acute hypersensitivity reactions attributed to RP1 or nivolumab or any of its excipients
Has received prior radiotherapy within 2 weeks of start of study treatment. Patients must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A one-week washout is permitted for palliative radiation (≤ 2 weeks of radiotherapy) to non-CNS disease.
Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacille Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed. Note: Available COVID-19 vaccines do not contain live virus (see Section 7.0).
Has acute or chronic active hepatitis B and C virus infection or known history of hepatitis B (defined as hepatitis B surface antigen [HBsAg] reactive) or known active hepatitis C virus (HCV) (defined as HCV RNA [qualitative]) or HIV infection. Note: No testing for hepatitis B, hepatitis C, or HIV is required unless mandated by local health authority or clinically indicated
With active significant herpetic infections or prior complications of HSV-1 infection (e.g., herpetic keratitis or encephalitis).
Had systemic infection requiring intravenous (IV) antibiotics or other serious infection within 14 days prior to dosing.
Is a person deprived of their liberty by a judicial or administrative decision, or an adult person subject to a legal protection measure.
Germany-specific additions: Patients requiring chronic use of systemic (oral or IV) antiviral medication with known antiherpetic activity (e.g., acyclovir).
Germany-specific additions: Has known hypersensitivity to contrast agent and its excipients or inability to undergo contrast-mediated imaging.
Phase 1 Expansion and Phase 2 patients only: 22. Treatment with botanical preparations (e.g., herbal supplements or traditional Chinese medicines) intended for general health support or to treat the disease under study within 2 weeks prior to first dose and throughout the study.
Phase 1 Expansion and Phase 2 patients only: Patients with an active, known, or suspected autoimmune disease. Patients with Type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
Phase 1 Expansion and Phase 2 patients only: May not have a history of life-threatening toxicity related to prior immune therapy except those that are unlikely to recur with standard countermeasures (e.g., hormone replacement after adrenal crisis).
Systemic anticancer therapies, excluding PD1/PD-L1 directed therapy alone or in combination, within 4 weeks prior to enrollment or 5 half-lives, whichever is shorter, before the first administration of RP1 or has not recovered from all AEs due to previous therapies to CTCAE Grade 1 or baseline. Note: Patients with toxicities after prior anticancer therapies that are not considered a likely safety risk such as Grade ≤ 2 neuropathy or alopecia, or immune mediated AEs that are unlikely to recur with standard countermeasures (e.g., hormone replacement after adrenal crisis, stable endocrine insufficiencies such as thyroid and adrenal insufficiency), are an exception to this criterion and may qualify for the study in discussion with the Medical Monitor.
Conditions requiring treatment with immunosuppressive doses (> 10 mg daily prednisone or equivalent) of systemic corticosteroids other than for corticosteroid replacement therapy within 14 days of enrollment.
Active leptomeningeal disease or uncontrolled, untreated brain metastasis: Patients with a history of treated brain metastasis and, at the time of screening, asymptomatic stable CNS metastases are eligible, provided they meet all the following: a. Brain imaging at screening shows no evidence of interim progression for at least 4 weeks by repeat imaging, and clinically stable for at least 2 weeks b. Have measurable disease outside the CNS c. Only supratentorial metastases allowed d. No ongoing requirement for corticosteroids as therapy for CNS disease; anticonvulsants at a stable dose allowed e. No stereotactic or whole-brain radiation within 14 days prior to first dose of study drug.
Major surgery ≤ 2 weeks prior to starting study drug. Note: Patients who undergo major surgery must have recovered prior to starting study treatment.
Any active malignancy ≤ 3 years before enrollment except for the specific cancer under investigation in this study and locally recurring cancer that has been treated curatively (e.g., resected basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast).
Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis
Has a history or current evidence of any condition, therapy, or laboratory abnormality that will be unfavorable for the administration of study drug or affect the explanation of drug toxicity or AEs, or 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.

The study team makes the final eligibility decision.

Where it's taking place

United Kingdom
United States

Questions & answers

Do participants get paid in this trial?

This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.

Is it free to join, and do I need insurance?

Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.

How long does this study last?

The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.

Who can join this trial?

This study is enrolling all sexes, 18-64 years, 65+ years. The study team makes the final eligibility decision.

Where is this trial taking place?

Study sites include United Kingdom; United States. Enter your location above to see the nearest site and check your eligibility.

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BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.