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

Replimune

Status and phase

Withdrawn

Phase 2

Conditions

Squamous Cell Carcinoma of Head and Neck

Recurrent Head and Neck Squamous Cell Carcinoma

Locally Advanced Head and Neck Squamous Cell Carcinoma

Treatments

Biological: RP3

Other: CCRT(concurrent chemoradiation therapy)

Other: carboplatin and paclitaxel

Biological: nivolumab

Study type

Interventional

Funder types

Industry

Identifiers

NCT05743270

RP3-002

Details and patient eligibility

About

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.

Full 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 kill tumor cells and generate a systemic anti-tumor immune response

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Histological diagnosis of squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx or of a lymph node(s) anywhere in levels I to V of the neck that has been excluded clinically from association with cancer from a non-head and neck site
All patients Must be willing to consent to provide archival or fresh tumor biopsy samples obtained within 60 days prior to initiation of study treatment. Patients must also consent to provide on-treatment biopsies as per protocol.
At least 1 measurable lesion of ≥ 1 cm in longest diameter (or shortest diameter for lymph nodes), in accordance with RECIST.
At least injectable tumors of at least 1 cm in aggregate overall longest diameter.
Have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 -1.

Locally Advanced Cohort Only

• patients must not be amenable to surgery with curative intent

Previously untreated high-risk disease meeting at least 1 of the following criteria:

Oral cavity, hypopharynx, larynx, oropharynx (p16 negative): Stage III/ IV Note: Cancers of the oral cavity, hypopharynx, and larynx are eligible irrespective of p16 status. These patients will not be stratified by p16 status.
For p16 positive oropharynx cancers, patients must have either
- T3 and/or N2 or greater disease with active smoking and/or greater than 20 pack year smoking history OR
- T4 and/or N3 disease irrespective of tobacco use
SCCHN of unknown primary Stage III/IV irrespective of p16 status or smoking status.
Eligible for definitive CCRT with curative intent.

R/M Cohort Only

Has recurrent or metastatic SCCHN eligible for first line systemic therapy for R/M disease.
Has a PD-L1 CPS <20.

Exclusion criteria

Primary tumors of nasopharynx, paranasal sinuses, nasal passages, salivary gland, thyroid or parathyroid gland, or skin.
Tumors with histopathology indicating the tumor has sarcomatous, sarcomatoid, verrucous, mixed, undifferentiated, or otherwise nonsquamous components.
Has an airway that is not deemed safe and stable on flexible fiberoptic laryngoscopy (FFL) performed by a head & neck cancer specialist within 7 days of first RP3 injection.
Has a baseline serum albumin (at Screening) <2.5 g/dL and/or evidence of cachexia or muscle wasting during physical exam at Screening.
Known acute or chronic hepatitis B or acute or chronic hepatitis C
Systemic infection requiring intravenous (IV) antibiotics
Active significant herpetic infections or prior complications of HSV-1 infection (eg, herpetic keratitis or encephalitis)
History of interstitial lung disease.
History of (noninfectious) pneumonitis that required steroids or has current pneumonitis.
Patients who require intermittent or chronic use of systemic (oral or IV) antivirals with known antiherpetic activity (eg, acyclovir).
Administration of live vaccine within 28 days prior to the first dose of study treatment.
History of allergy or sensitivity to study drug components or prior monoclonal antibody treatment.
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
History of viral infections according to the protocol
Treatment with botanical preparations within 2 weeks prior to treatment.
Major surgery ≤ 2 weeks prior to starting study treatment.

LA Cohort only

Has received prior radiotherapy for SCCHN.
Has received any prior systemic therapy for SCCHN.

R/M cohort only

Is eligible for radiation and/or surgery with curative intent.
Has received systemic therapy for recurrence or new (ie, not present at the time of initial diagnosis) metastases of SCCHN.
Received a paclitaxel-containing regimen as part of frontline treatment (prior to R/M disease) with a documented best response of stable disease (SD) or PD (patients who achieved a partial response [PR] or CR are eligible).
Received a carboplatin-containing regimen as part of frontline treatment (prior to R/M disease) with a documented best response of SD or PD (patients who achieved PR or CR are eligible).
Patients with known intolerance to carbo-platinum and/or paclitaxel, including hypersensitivity to Cremophor® EL (polyoxyethylated castor oil).
Previously received multiple courses of irradiation to the same anatomic site unless such patient has nondoubly-irradiated, measurable, injectable lesions, which are the only lesions to be used as target lesions (for nodal disease, only lesions in nodal basins that have been previously irradiated just once or not irradiated at all may be injected and/or used as target lesions).

Note: Other protocol defined inclusion/exclusion criteria apply for each cohort

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Sequential Assignment

Masking

None (Open label)

0 participants in 3 patient groups

LA Cohort: RP3 in combination with CCRT followed by nivolumab in Locally Advanced SCCHN

Experimental group

Description:

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.

Treatment:

Biological: nivolumab

Other: CCRT(concurrent chemoradiation therapy)

Biological: RP3

LA Cohort: concurrent chemoradiation therapy in Patients With Locoregionally Advanced SCCHN

Active Comparator group

Description:

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

Treatment:

Other: CCRT(concurrent chemoradiation therapy)

R/M Cohort:RP3 in combination with carboplatin, paclitaxel and then nivolumab in R/M SCCHN

Experimental group