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RP3 + Nivolumab Combination Therapy for Head and Neck Cancers

Recruiting at 36 trial locations
CT
Overseen ByClinical Trials at Replimune
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial

Trial Summary

What is the purpose of this trial?

This trial uses a modified virus called RP3 to treat advanced head and neck cancers that cannot be removed by surgery. The virus kills cancer cells and helps the immune system fight the cancer.

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.

What data supports the effectiveness of the RP3 + Nivolumab combination therapy for head and neck cancers?

Research shows that the combination of paclitaxel and carboplatin, which are part of the RP3 + Nivolumab therapy, was effective in treating advanced head and neck cancer, with a 39% overall response rate in heavily pretreated patients. Additionally, previous use of nivolumab, an immune checkpoint inhibitor, is common in treating recurrent head and neck cancers, suggesting its potential benefit in combination therapies.12345

Is the RP3 + Nivolumab combination therapy generally safe for humans?

The combination of paclitaxel and carboplatin, which are part of the RP3 + Nivolumab therapy, has been studied in head and neck cancer patients and shown to have tolerable side effects, though some patients experienced significant side effects like neutropenia (low white blood cell count) and mucositis (painful inflammation of the mouth lining). Nivolumab, also part of the therapy, has been used in similar combinations and was generally well tolerated, but some patients experienced serious side effects like anemia and high blood pressure.56789

What makes the RP3 + Nivolumab combination therapy unique for head and neck cancers?

The RP3 + Nivolumab combination therapy is unique because it combines an immune checkpoint inhibitor (Nivolumab) with chemotherapy agents (Carboplatin and Paclitaxel), potentially enhancing the immune system's ability to fight cancer while directly targeting cancer cells, which is different from standard treatments that typically use chemotherapy alone or in combination with other drugs.23101112

Research Team

DC

David Cohan, MD/FACS

Principal Investigator

Replimune Inc.

Eligibility Criteria

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.
See 14 more

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).
See 24 more

Timeline

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

Treatment Details

Interventions

  • Carboplatin
  • Nivolumab
  • Paclitaxel
  • RP3
Trial OverviewThe 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.
Participant Groups
3Treatment groups
Experimental Treatment
Active Control
Group I: R/M Cohort:RP3 in combination with carboplatin, paclitaxel and then nivolumab in R/M SCCHNExperimental Treatment3 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 SCCHNExperimental Treatment3 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 SCCHNActive Control1 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

Find a Clinic Near You

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 profile image

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 profile image

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

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

Findings from Research

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.
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.
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]
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.
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]

References

Analysis of cell-cycle checkpoint pathways in head and neck cancer cell lines: implications for therapeutic strategies. [2019]
Phase II trial of a paclitaxel-carboplatin combination in recurrent squamous cell carcinoma of the head and neck. [2017]
Impact of previous nivolumab treatment on the response to taxanes in patients with recurrent/metastatic head and neck squamous cell carcinoma. [2021]
Paclitaxel and carboplatin in head and neck cancer. [2015]
Effectiveness of paclitaxel and carboplatin combination in heavily pretreated patients with head and neck cancers. [2019]
Phase I/II study of paclitaxel/cisplatin as first-line therapy for locally advanced head and neck cancer. [2015]
Paclitaxel, carboplatin, and concomitant radiotherapy for resected patients with high risk head and neck cancer. [2015]
Survival outcomes in patients with oropharyngeal cancer treated with carboplatin/paclitaxel and concurrent radiotherapy. [2018]
Safety and preliminary activity of pembrolizumab-carboplatin-paclitaxel in heavily pretreated and/or fragile patients with PDL1-positive recurrent/metastatic head and neck cancer. [2023]
Efficacy of Nivolumab and Pembrolizumab in Platinum-sensitive Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma. [2023]
Nivolumab for Platinum-refractory and -sensitive Recurrent and Metastatic Head and Neck Squamous Cell Carcinoma. [2022]
Chemotherapy for recurrent/metastatic head and neck cancers. [2019]