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NCT03767348 · CITED IN SOURCE DOCUMENTS

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

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase
PHASE2
Status at capture
ACTIVE NOT RECRUITING
Registry last update
2026-02-13

The Phase 2 study is a multicenter, open-label study of RP1 to further investigate safety and to estimate the efficacy of RP1 at the RP2D in combination with nivolumab in patients with Stage IIIb-IV unresectable melanoma, microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) solid tumors, non-melanoma skin cancer (NMSC), and non-small cell lung cancer (NSCLC).

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

No posted result sections were captured. Registered plans do not establish that a treatment works.

Who could take part
eligibility Criteria
Key Inclusion Criteria: * Have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1. * At least one measurable and injectable lesion * Have provided a former tumor pathology specimen or be willing to supply a new tumor sample from a biopsy * Have a predicted life expectancy of ≥ 3 months * Measurable disease, according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria * Subjects with MSI-H or dMMR tumors: has diagnosis of MSI-H or metatstatic dMMR tumor (according to protocol definition) who has progressed on prior anti-PD1/PD-L1 therapy. * Subjects with NMSC: has diagnosis of locally advanced or metastatic NMSC that are not considered treatable by surgery including basal cell carcinoma, cutaneous squamous cell carcinoma, basosquamous carcinoma, Merkel cell carcinoma and other non-melanoma skin cancers (per protocol). Patients must have received 8 weeks of anti-PD1/PD-L1 as their last line of therapy and progressed while on treatment. * Subjects with anti-PD1 failed cutaneous melanoma: has confirmed progressive disease while on anti-PD1 treatment for at least 8 weeks and documented BRAF mutation status * Subjects with anti-PD1 failed NSCLC: 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 given must have included an anti-PD1/PD-L1 directed therapy with radiologic disease progression on or after treatment. Key Exclusion Criteria: * Prior treatment with an oncolytic therapy * History of viral infections according to the protocol * Prior complications with herpes infections * Chronic use of anti-virals * Uncontrolled/untreated brain metastasis * History of interstitial lung disease * History of non-infectious pneumonitis * History of clinically significant cardiovascular disease
healthy Volunteers
false
minimum Age
18 Years
sex
ALL
std Ages
  1. ADULT
  2. OLDER_ADULT
Treatment arms and interventions
arm Groups
  1. description
    anti-PD-1 monoclonal antibody
    intervention Names
    1. Biological: RP1
    label
    Dose escalation of RP1 by intratumoral (IT) injection in superficial tumors
    type
    EXPERIMENTAL
  2. description
    Dose escalation of RP1 alone in 3 cohorts with IT injections in superficial tumors
    intervention Names
    1. Biological: RP1
    label
    Dose escalation of RP1 by intratumoral (IT) injection in deep/visceral tumors
    type
    EXPERIMENTAL
  3. description
    Dose escalation of RP1 alone in 3 cohorts with IT injections in superficial tumors
    intervention Names
    1. Biological: RP1
    2. Biological: nivolumab
    label
    Dose expansion of RP1 and nivolumab (IV) in superficial tumors
    type
    EXPERIMENTAL
  4. description
    Doses of RP1 (IT) in deep/visceral tumors with nivolumab (IV)
    intervention Names
    1. Biological: RP1
    2. Biological: nivolumab
    label
    Dose expansion of RP1 and nivolumab (IV) in deep/visceral tumors
    type
    EXPERIMENTAL
  5. description
    Doses of RP1 (IT) in superficial or deep tumors with nivolumab (IV) in subjects with melanoma
    intervention Names
    1. Biological: RP1
    2. Biological: nivolumab
    label
    RP1 (IT) and nivolumab (IV) in melanoma
    type
    EXPERIMENTAL
  6. description
    Doses of RP1 (IT) in superficial or deep tumors with nivolumab (IV) in subjects with MSI-H or dMMR solid tumors
    intervention Names
    1. Biological: RP1
    2. Biological: nivolumab
    label
    RP1 (IT) and nivolumab (IV) in MSI-H/dMMR solid tumors
    type
    EXPERIMENTAL
  7. description
    Doses of RP1 (IT) in superficial or deep tumors with nivolumab (IV) in subjects with non-melanoma skin cancer
    intervention Names
    1. Biological: RP1
    2. Biological: nivolumab
    label
    RP1 (IT) and nivolumab (IV) in NMSC
    type
    EXPERIMENTAL
  8. description
    Doses of RP1 (IT) in superficial or deep tumors with nivolumab (IV) in subjects with cutaneous melanoma who have been previously treated with anti-PD1 therapy
    intervention Names
    1. Biological: RP1
    2. Biological: nivolumab
    label
    RP1(IT) and nivolumab (IV) in anti-PD1 Failed Cutaneous Melanoma
    type
    EXPERIMENTAL
  9. description
    Doses of RP1 (IT) in superficial or deep tumors with nivolumab (IV) in subjects with non-melanoma skin cancer who have been previously treated with anti-PD1/PD-L1 therapy
    intervention Names
    1. Biological: RP1
    2. Biological: nivolumab
    label
    RP1(IT) and nivolumab (IV) in anti-PD1/PD-L1 Failed NMSC
    type
    EXPERIMENTAL
  10. description
    Doses of RP1 (IT) in superficial or deep tumors with nivolumab (IV) in subjects with non small cell lung cancer who have been previously treated with anti-PD1/PD-L1 therapy
    intervention Names
    1. Biological: RP1
    2. Biological: nivolumab
    label
    RP1(IT) and nivolumab (IV) in anti-PD1/PD-L1 Failed NSCLC
    type
    EXPERIMENTAL
interventions
  1. arm Group Labels
    1. Dose escalation of RP1 by intratumoral (IT) injection in deep/visceral tumors
    2. Dose escalation of RP1 by intratumoral (IT) injection in superficial tumors
    3. Dose expansion of RP1 and nivolumab (IV) in deep/visceral tumors
    4. Dose expansion of RP1 and nivolumab (IV) in superficial tumors
    5. RP1 (IT) and nivolumab (IV) in MSI-H/dMMR solid tumors
    6. RP1 (IT) and nivolumab (IV) in NMSC
    7. RP1 (IT) and nivolumab (IV) in melanoma
    8. RP1(IT) and nivolumab (IV) in anti-PD1 Failed Cutaneous Melanoma
    9. RP1(IT) and nivolumab (IV) in anti-PD1/PD-L1 Failed NMSC
    10. RP1(IT) and nivolumab (IV) in anti-PD1/PD-L1 Failed NSCLC
    description
    Genetically modified herpes simplex type 1 virus
    name
    RP1
    type
    BIOLOGICAL
  2. arm Group Labels
    1. Dose expansion of RP1 and nivolumab (IV) in deep/visceral tumors
    2. Dose expansion of RP1 and nivolumab (IV) in superficial tumors
    3. RP1 (IT) and nivolumab (IV) in MSI-H/dMMR solid tumors
    4. RP1 (IT) and nivolumab (IV) in NMSC
    5. RP1 (IT) and nivolumab (IV) in melanoma
    6. RP1(IT) and nivolumab (IV) in anti-PD1 Failed Cutaneous Melanoma
    7. RP1(IT) and nivolumab (IV) in anti-PD1/PD-L1 Failed NMSC
    8. RP1(IT) and nivolumab (IV) in anti-PD1/PD-L1 Failed NSCLC
    description
    anti-PD-1 monoclonal antibody
    name
    nivolumab
    other Names
    1. Opdivo
    type
    BIOLOGICAL
Study design
allocation
NON_RANDOMIZED
intervention Model
PARALLEL
masking Info
masking
NONE
primary Purpose
TREATMENT
Enrollment
count
340
type
ESTIMATED
Registered outcome plans (not posted results)
primary Outcomes
  1. description
    Percentage of subjects with adverse events (AEs)
    measure
    Percentage of adverse events (AEs)
    time Frame
    26 months
  2. description
    Percentage of subjects with serious adverse events (SAEs)
    measure
    Percentage of serious adverse events (SAEs)
    time Frame
    26 months
  3. description
    Percentage of subjects with dose limiting toxicities (DLTs)
    measure
    Percentage of dose limiting toxicities (DLTs)
    time Frame
    26 months
  4. description
    Percentage of overall response rate (ORR) for all participants
    measure
    Percentage of overall response rate (ORR)
    time Frame
    26 months
  5. description
    Assess the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of RP1 based on the safety and response data collected during Phase 1 Escalation
    measure
    Maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of RP1
    time Frame
    20 weeks
secondary Outcomes
  1. description
    Percentage of subjects with biological activity determined by tumor biopsies and biomarker data
    measure
    Percentage of biologic activity
    time Frame
    20 weeks
  2. description
    Data gathered from blood, urine, swabs of injection site, dressings, and oral mucosa to determine the shedding and biodistribution of RP1
    measure
    Percentage subjects with detectable RP1
    time Frame
    20 weeks
  3. description
    Percentage of subjects with a complete response (CR)
    measure
    Percentage of complete response (CR)
    time Frame
    26 months
  4. description
    Median duration of response of subjects
    measure
    Median duration of response
    time Frame
    26 months
  5. description
    Median duration of progression-free survival of subjects
    measure
    Median progression-free survival
    time Frame
    26 months
  6. description
    Median overall survival rate of subjects
    measure
    Median overall survival
    time Frame
    26 months
Full study description
brief Summary
The Phase 2 study is a multicenter, open-label study of RP1 to further investigate safety and to estimate the efficacy of RP1 at the RP2D in combination with nivolumab in patients with Stage IIIb-IV unresectable melanoma, microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) solid tumors, non-melanoma skin cancer (NMSC), and non-small cell lung cancer (NSCLC).
Source references
references
  1. citation
    Wong MK, Milhem MM, Sacco JJ, Michels J, In GK, Munoz Couselo E, Schadendorf D, Beasley GM, Niu J, Chmielowski B, Wise-Draper TM, Bowles TL, Tsai KK, Lebbe C, Gaudy-Marqueste C, Middleton MR, Skolariki A, Samson A, Chesney JA, VanderWalde AM, Zakharia Y, Harrington KJ, Appleton E, Bommareddy PK, Zhu J, Viana M, Hou JW, Coffin RS, Robert C. RP1 Combined With Nivolumab in Advanced Anti-PD-1-Failed Melanoma (IGNYTE). J Clin Oncol. 2025 Nov 20;43(33):3589-3599. doi: 10.1200/JCO-25-01346. Epub 2025 Jul 8.
    pmid
    40627813
    type
    DERIVED
  2. citation
    Thomas S, Kuncheria L, Roulstone V, Kyula JN, Mansfield D, Bommareddy PK, Smith H, Kaufman HL, Harrington KJ, Coffin RS. Development of a new fusion-enhanced oncolytic immunotherapy platform based on herpes simplex virus type 1. J Immunother Cancer. 2019 Aug 10;7(1):214. doi: 10.1186/s40425-019-0682-1.
    pmid
    31399043
    type
    DERIVED
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        14 CLINICAL STUDIES The efficacy of TUDRIQEV in combination with nivolumab was evaluated in an open-label, multiregional, single-arm study (IGNYTE; NCT03767348). The study enrolled adult patients with stage IIIB, IIIC, or IV unresectable advanced melanoma who had previously been treated with at least eight consecutive
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    Preserved source evidence · Not medical advice