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

Replimune

Status and phase: Active, not recruiting; Phase 2

Conditions: Microsatellite Instability-High (MSI-H); Non-melanoma Skin Cancer (NMSC); Non-Small Cell Lung Cancer (NSCLC); Cutaneous Melanoma

Treatments: Biological: RP1; Biological: nivolumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT03767348

RPL-001-16

2024-511728-15-00 (EU Trial (CTIS) Number)

2016-004548-12 (EudraCT Number)

Details and patient eligibility

About

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).

Enrollment: 340 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

340 participants in 10 patient groups

Dose escalation of RP1 by intratumoral (IT) injection in superficial tumors

Experimental group

Description:

anti-PD-1 monoclonal antibody

Treatment:

Biological: RP1

Dose escalation of RP1 by intratumoral (IT) injection in deep/visceral tumors

Experimental group

Description:

Dose escalation of RP1 alone in 3 cohorts with IT injections in superficial tumors

Treatment:

Biological: RP1

Dose expansion of RP1 and nivolumab (IV) in superficial tumors

Experimental group

Description:

Dose escalation of RP1 alone in 3 cohorts with IT injections in superficial tumors

Treatment:

Biological: nivolumab

Biological: RP1

Dose expansion of RP1 and nivolumab (IV) in deep/visceral tumors

Experimental group

Description:

Doses of RP1 (IT) in deep/visceral tumors with nivolumab (IV)

Treatment:

Biological: nivolumab

Biological: RP1

RP1 (IT) and nivolumab (IV) in melanoma

Experimental group

Description:

Doses of RP1 (IT) in superficial or deep tumors with nivolumab (IV) in subjects with melanoma

Treatment:

Biological: nivolumab

Biological: RP1

RP1 (IT) and nivolumab (IV) in MSI-H/dMMR solid tumors

Experimental group

Description:

Doses of RP1 (IT) in superficial or deep tumors with nivolumab (IV) in subjects with MSI-H or dMMR solid tumors

Treatment:

Biological: nivolumab

Biological: RP1

RP1 (IT) and nivolumab (IV) in NMSC

Experimental group

Description:

Doses of RP1 (IT) in superficial or deep tumors with nivolumab (IV) in subjects with non-melanoma skin cancer

Treatment:

Biological: nivolumab

Biological: RP1

RP1(IT) and nivolumab (IV) in anti-PD1 Failed Cutaneous Melanoma

Experimental group

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

Treatment:

Biological: nivolumab

Biological: RP1

RP1(IT) and nivolumab (IV) in anti-PD1/PD-L1 Failed NMSC

Experimental group

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

Treatment:

Biological: nivolumab

Biological: RP1

RP1(IT) and nivolumab (IV) in anti-PD1/PD-L1 Failed NSCLC

Experimental group

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

Treatment:

Biological: nivolumab

Biological: RP1