RP3 + Nivolumab Combination Therapy for Head and Neck Cancers

No longer recruiting at 39 trial locations

Overseen By Clinical Trials at Replimune

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Replimune Inc.

Must not be taking: Antivirals

Disqualifiers: Hepatitis, Pneumonitis, Herpetic infections, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 52 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments for individuals with advanced head and neck cancers that cannot be surgically removed. It combines RP3 (an experimental treatment) with other therapies, such as nivolumab (an immunotherapy drug) and chemotherapy, to evaluate their combined effectiveness. The trial includes two groups: one for those whose cancer has recurred or spread, and another for those with locally advanced cancer. It is suitable for individuals with squamous cell carcinoma in areas like the mouth, throat, or voice box who seek new treatment options. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Do I need to stop taking my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you require systemic antivirals or have had a live vaccine within 28 days before starting the study treatment.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that RP3, when combined with treatments like carboplatin and paclitaxel, is still under investigation for safety in humans. Previous studies tested RP3 in individuals with head and neck cancers, but they did not confirm the treatment's safety or tolerability.

As a Phase 2 study, the treatment has already passed initial safety tests in earlier trials, indicating prior human testing. However, researchers continue to assess its safety. RP3 is not yet FDA-approved for any condition, so its safety remains under evaluation.

Participants should understand that while earlier trials provide some evidence, the complete safety of RP3 with these drugs is not yet known. Consulting healthcare professionals is crucial to fully understand potential risks and benefits. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about RP3 in combination with nivolumab for head and neck cancers because it introduces a novel approach to treatment. Unlike standard therapies such as surgery, radiation, or chemotherapy alone, RP3 is delivered directly into tumors through intratumoral injection, which could enhance its ability to target and destroy cancer cells precisely. Additionally, RP3 works in tandem with nivolumab, an immunotherapy drug, to potentially boost the immune system's response against cancer cells. This dual-action strategy may offer more effective results compared to traditional treatments, sparking anticipation in the medical community.

What evidence suggests that this trial's treatments could be effective for head and neck cancers?

This trial will evaluate the effectiveness of combining RP3 with carboplatin, paclitaxel, and nivolumab in treating advanced head and neck cancers. Research has shown that using paclitaxel and carboplatin together results in a 54% overall response rate in patients with these cancers. RP3, which participants in this trial may receive, kills cancer cells and boosts the body's immune system to fight the cancer. This can cause an "abscopal effect," where not only the treated tumor shrinks, but other tumors in the body may shrink as well. When combined with nivolumab, another treatment option in this trial that enhances immune system function, the treatment aims to further strengthen this immune response, potentially leading to better results for patients. ^{2 4 5 6 7}

Who Is on the Research Team?

David Cohan, MD/FACS

Principal Investigator

Replimune Inc.

Are You a Good Fit for This Trial?

This trial is for adults with advanced, inoperable head and neck squamous cell carcinomas (SCCHN), including oral cavity or throat cancers. Participants must have a measurable lesion, be willing to provide tumor samples, and have an ECOG performance status of 0-1. Exclusions include history of severe pneumonitis, allergies to study drugs, prior treatments targeting T-cell pathways, eligibility for curative surgery/radiation, certain viral infections or recent major surgery.

Inclusion Criteria

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.

Exclusion Criteria

You have had lung inflammation in the past that required steroids or currently have lung inflammation.

You have had an allergic reaction or sensitivity to the study drug's components or a previous monoclonal antibody treatment.

Patients who require intermittent or chronic use of systemic (oral or IV) antivirals with known antiherpetic activity (eg, acyclovir).

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive RP3 in combination with concurrent chemoradiation therapy followed by nivolumab for the LA Cohort or combined with chemotherapy and nivolumab for the R/M Cohort

Up to 52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 3 years

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Nivolumab
• Paclitaxel
• RP3

Trial Overview The trial studies RP3 combined with chemoradiation therapy followed by nivolumab for locally advanced cases or combined with chemotherapy and nivolumab for recurrent/metastatic cases. It's a Phase 2 study split into two cohorts based on the stage of cancer: one cohort has locoregionally advanced disease while the other has recurrent/metastatic disease.

How Is the Trial Designed?

Group I: R/M Cohort:RP3 in combination with carboplatin, paclitaxel and then nivolumab in R/M SCCHN Experimental Treatment 3 Interventions

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.

Group II: LA Cohort: RP3 in combination with CCRT followed by nivolumab in Locally Advanced SCCHN Experimental Treatment 3 Interventions

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.

Group III: LA Cohort: concurrent chemoradiation therapy in Patients With Locoregionally Advanced SCCHN Active Control 1 Intervention

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

Carboplatin is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Paraplatin for:

• Ovarian cancer
• Testicular cancer
• Lung cancer
• Head and neck cancer
• Brain cancer

Approved in European Union as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular cancer

Who Is Running the Clinical Trial?

Replimune Inc.

Lead Sponsor

Trials

16

Recruited

1,700+

Bristol-Myers Squibb

Industry Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

Published Research Related to This Trial

In a phase II study involving 24 heavily pretreated patients with advanced head and neck cancer, the combination of paclitaxel and carboplatin resulted in an overall response rate of 39%, with 17% achieving a complete response and 22% a partial response.

The treatment was generally tolerable, although 79% of patients experienced neurotoxicity, and some had significant neutropenia, indicating that while effective, careful monitoring of side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of paclitaxel and carboplatin combination in heavily pretreated patients with head and neck cancers. Stathopoulos, GP., Rigatos, S., Papakostas, P., et al.[2019]

In a phase I/II study involving 28 patients with advanced head and neck carcinoma, the combination of escalating doses of paclitaxel and cisplatin resulted in a high overall response rate of 78%, with 13 complete responses and 8 partial responses.

The treatment was generally well-tolerated, with no dose-limiting hematologic toxicity observed, although some patients experienced mild to moderate side effects like paresthesia and myalgias.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I/II study of paclitaxel/cisplatin as first-line therapy for locally advanced head and neck cancer. Hitt, R., Paz-Ares, L., Hidalgo, M., et al.[2015]

In a study of 160 patients with advanced oropharyngeal squamous cell carcinoma treated with carboplatin, paclitaxel, and radiation over 10 years, the overall survival rates were 81.7% at 3 years and 70.7% at 5 years, indicating effective treatment outcomes.

The treatment demonstrated an acceptable side effect profile, with the most common adverse effect being acute dysphagia (75.25%), and only 11.9% of patients experiencing significant hematologic toxicities, suggesting carboplatin may be a safer alternative to cisplatin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Survival outcomes in patients with oropharyngeal cancer treated with carboplatin/paclitaxel and concurrent radiotherapy. Roskies, M., Kay-Rivest, E., Mascarella, MA., et al.[2018]

In a small retrospective study of 10 patients with recurrent or metastatic squamous cell carcinoma of the head and neck, the combination of pembrolizumab with carboplatin and paclitaxel (pembro + CP) was well tolerated, with 100% of patients experiencing mild adverse events and 30% experiencing more severe side effects.

The overall response rate (ORR) was 14% with one complete response, and the disease control rate (DCR) was 43%, indicating that while the treatment showed some effectiveness, further prospective studies are needed to fully evaluate its safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and preliminary activity of pembrolizumab-carboplatin-paclitaxel in heavily pretreated and/or fragile patients with PDL1-positive recurrent/metastatic head and neck cancer. Cabezas-Camarero, S., Merino-Menéndez, S., Cabrera-Martín, MN., et al.[2023]

In a phase I trial involving 33 patients with advanced head and neck cancer, the combination of paclitaxel and carboplatin demonstrated a 54% overall response rate, with 27% achieving complete responses, indicating significant efficacy in treating this patient population.

The maximum tolerated dose of paclitaxel was determined to be between 230 and 265 mg/m2, with manageable side effects, primarily grade 3/4 neutropenia and thrombocytopenia, suggesting that this treatment can be safely administered while potentially enhancing organ preservation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel and carboplatin in head and neck cancer. Dunphy, F., Boyd, J., Dunleavy, T.[2015]

In a study of 185 patients with recurrent and/or metastatic head and neck squamous cell carcinoma, those who received nivolumab before taxane treatment showed a significantly higher objective response rate (39.4%) compared to those who did not receive nivolumab (26.3%).

The disease control rate was also better in the post-nivolumab group (69% vs. 50%), suggesting that taxane monotherapy may be an effective third-line treatment option after nivolumab, especially for patients who cannot benefit from first-line pembrolizumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of previous nivolumab treatment on the response to taxanes in patients with recurrent/metastatic head and neck squamous cell carcinoma. Guiard, E., Clatot, F., Even, C., et al.[2021]

Chemotherapy remains the primary treatment for recurrent and metastatic head and neck squamous cell carcinoma, with the current standard being a combination of cisplatin, 5-fluorouracil, and cetuximab for fit patients.

Immunotherapy options like nivolumab and pembrolizumab have become new standards in second-line treatment, showing improved overall survival, but further research is needed to identify predictive markers for patient selection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemotherapy for recurrent/metastatic head and neck cancers. Karabajakian, A., Toussaint, P., Neidhardt, EM., et al.[2019]

In a study of platinum-sensitive recurrent or metastatic head and neck squamous cell carcinomas involving 36 patients, both nivolumab and pembrolizumab showed effectiveness, with median overall survival of 16.9 months for nivolumab and 19.2 months for pembrolizumab, indicating similar efficacy between the two treatments.

The median progression-free survival was 4.8 months for nivolumab and 9.3 months for pembrolizumab, with objective response rates of 38% and 47%, respectively, suggesting that both drugs are viable options for treatment in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Nivolumab and Pembrolizumab in Platinum-sensitive Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma. Yamashita, G., Okamoto, I., Ito, T., et al.[2023]

Paclitaxel was found to be more effective than carboplatin in inducing cell death (apoptosis) and inhibiting growth of head and neck squamous cell carcinoma (HNSCC) cells, with its action linked to increased cyclin B1/CDC2 activity and prolonged mitotic arrest.

Combining paclitaxel and carboplatin, either simultaneously or sequentially, resulted in greater inhibition of cell growth compared to using either drug alone, highlighting the potential for enhanced therapeutic strategies in treating HNSCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of cell-cycle checkpoint pathways in head and neck cancer cell lines: implications for therapeutic strategies. Coleman, SC., Stewart, ZA., Day, TA., et al.[2019]

In a study of 27 patients with recurrent squamous cell carcinoma of the head and neck, the combination of paclitaxel and carboplatin showed an objective response rate of 29.6%, with a median response duration of 4.2 months.

However, the treatment was associated with significant toxicities, including high rates of neutropenia (62.9%) and other severe side effects, indicating a need for safer chemotherapy alternatives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of a paclitaxel-carboplatin combination in recurrent squamous cell carcinoma of the head and neck. Pivot, X., Cals, L., Cupissol, D., et al.[2017]

Citations

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A phase 2, open-label, multicenter study investigating ... Intratumoral (IT) RP3 delivery may promote immunogenic tumor cell death and systemic antitumor response (abscopal effect), both of which may be further enhanced ...

2. withpower.com withpower.com/trial/phase-2-carcinoma-4-2023-fb1d0

RP3 + Nivolumab Combination Therapy for Head and ... In a phase I trial involving 33 patients with advanced head and neck cancer, the combination of paclitaxel and carboplatin demonstrated a 54% overall ...

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An open-label, multicenter, phase 1 study of RP3 as a ... A phase 2, open-label, multicenter study investigating efficacy and safety of RP3 oncolytic immunotherapy combined with other therapies in ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04735978

NCT04735978 | Study of RP3 Monotherapy and ... This is a Phase 1, multicenter, open label, single agent dose escalation and combination treatment study of RP3 in adult participants with advanced solid ...

5. trial.medpath.com trial.medpath.com/clinical-trial/ebd86085db49aa28/nct05743270-oncolytic-immunotherapy-squamous-cell-carcinoma-head-neck

Study of RP3 in Combination With Nivolumab and Other ... LA Cohort: Summary of Patient-Reported Outcomes Measured by FACT-HNSI-22, From Day 1 to 52 Weeks. FACT-HNSI-22 is a Functional Assessment of Cancer Therapy Head ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.TPS6106

A phase 2, open-label, multicenter study investigating ... This phase 2 study will evaluate the efficacy and safety of RP3 combined with other therapies in pts with advanced, inoperable LA or R/M SCCHN.

7. ir.replimune.com ir.replimune.com/node/9226/pdf

Replimune Announces Positive Initial Data from the Anti- ... Three Phase 2 clinical trials are to be conducted with RP2/3, each initiating in the first half of 2023. Squamous cell carcinoma of the head and ...