A Phase 3 Open-Label, Randomized Study of PDS0101 and Pembrolizumab vs Pembrolizumab Alone in First-Line Treatment of Unresectable Recurrent and/or Metastatic HPV16+ Head and Neck Squamous Cell Carcinoma

Plain English Summary

Phase 3 Study of PDS0101 and Pembrolizumab in HPV16+ Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma is a Phase 3 clinical trial sponsored by PDS Biotechnology Corp. studying Recurrent Head and Neck Cancer, Metastatic Head and Neck Cancer, HPV Positive Oropharyngeal Squamous Cell Carcinoma, Neoplasms, Head and Neck, Unresectable Head and Neck Squamous Cell Carcinoma. This study tests if a combination of PDS0101 and pembrolizumab is more effective than pembrolizumab alone for treating advanced head and neck cancer. It is for adults with head and neck cancer that has returned or spread, is unresectable (cannot be surgically removed), and is positive for the HPV16 virus. Participants will be randomly assigned to receive either the combination therapy or pembrolizumab alone. The study is open-label, meaning both patients and doctors will know which treatment is given. Alternative treatments may include other chemotherapy, radiation, or immunotherapy options depending on the patient's specific situation and prior treatments. The trial aims to enroll 252 participants.

Official Summary

This is a global, multi-center, Phase 3 study that is randomized 1:1, controlled, and open label to evaluate PDS0101 (Versamune + HPVMix) in combination with pembrolizumab vs. pembrolizumab monotherapy as first-line treatment in patients with unresectable recurrent or metastatic HPV16-positive HNSCC expressing programmed cell death ligand-1 (PD-L1) with combined positive score (CPS) ≥1.

Who Can Participate

Here is what you need to know about eligibility for this trial. Adults aged 18 and older with a confirmed diagnosis of recurrent or metastatic squamous cell cancer of the head and neck. Must have a primary tumor in the oropharynx, oral cavity, hypopharynx, or larynx, and the tumor must be positive for HPV16 and express PD-L1. Cannot have received prior systemic (body-wide) anti-cancer therapy for their current incurable recurrent or metastatic disease. Must have adequate organ function (blood counts, kidney, liver) and a good general health status (ECOG 0 or 1). This trial is studying Recurrent Head and Neck Cancer, Metastatic Head and Neck Cancer, HPV Positive Oropharyngeal Squamous Cell Carcinoma, Neoplasms, Head and Neck, Unresectable Head and Neck Squamous Cell Carcinoma, so participants generally need a confirmed diagnosis.

What They're Measuring

The primary outcomes measure how long patients live (Overall Survival) and how long they live without their cancer getting worse (Progression-Free Survival), indicating the potential benefit of the ne The specific primary outcome measures are: Overall Survival (OS) (Up to 54 months); Progression-Free Survival (PFS) (Up to 18 months). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 3, the final and most rigorous stage before seeking FDA approval. Phase 3 trials involve 300-3,000+ patients across multiple sites and compare the new treatment directly against the current standard of care. These pivotal trials generate the evidence needed for regulatory review. About 58% of Phase 3 drugs receive FDA approval. Successful Phase 3 results typically lead to a New Drug Application submission.

Why This Trial Matters

This trial addresses a critical need for more effective first-line treatments for patients with recurrent or metastatic HPV16-positive head and neck squamous cell carcinoma, a population with limited As a Phase 3 trial, positive results could directly lead to FDA approval, making this treatment available to the broader patient population. This research targets Recurrent Head and Neck Cancer, Metastatic Head and Neck Cancer, HPV Positive Oropharyngeal Squamous Cell Carcinoma, Neoplasms, Head and Neck, Unresectable Head and Neck Squamous Cell Carcinoma, where improved treatment options are needed.

Investor Insight

This Phase 3 trial, sponsored by PDS Biotechnology Corp., aims to establish a new standard of care for a specific subset of head and neck cancer patients, potentially leading to significant market pen Phase 3 trials have approximately a 50-60% chance of gaining FDA approval if they reach this stage.

Is This Trial Right for Me?

Ask your doctor about the specific risks and benefits of both treatment arms, and how this trial fits into your overall treatment plan. Participation involves regular clinic visits for treatment administration, monitoring, and tests. The study requires a commitment to follow-up assessments for several years. Be prepared for potential side effects and discuss any new or worsening symptoms with your healthcare team promptly. The trial is being conducted at 20 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: NONE
• Enrollment: 252 participants

Interventions

• COMBINATION_PRODUCT: Combination Treatment of PDS0101 and Pembrolizumab — * Pembrolizumab (IV) every 3 weeks for up to 35 Cycles * PDS0101 (SC) during Cycles 1, 2, 3, 4, and 12
• DRUG: Pembrolizumab Monotherapy — Pembrolizumab (IV) every 3 weeks for up to 35 cycles.

Primary Outcomes

• Overall Survival (OS) (Up to 54 months)
• Progression-Free Survival (PFS) (Up to 18 months)

Secondary Outcomes

• Objective Response Rate (ORR) (Up to 27 months)
• Disease Control Rate (DCR) (Up to 27 months)
• Duration of Response (DOR) (Up to 27 months)

Full Eligibility Criteria

Inclusion Criteria:

1. Subject (or legally acceptable representative, if applicable) provides written informed consent for the study.
2. Subject is ≥18 years of age on the day of signing the informed consent.
3. Have a history of histologically- or cytologically-confirmed diagnosis of recurrent and/or metastatic squamous cell cancer of the head and neck (HNSCC) with:

   1. Eligible primary tumor location of oropharynx, oral cavity, hypopharynx, or larynx.
   2. HPV16 tumor positivity (central testing).
   3. Tumor PD-L1 expression defined as a CPS ≥ 1 using the FDA- approved pembrolizumab (KEYTRUDA®) assay (local testing).
   4. No prior systemic anticancer therapy administered in the incurable recurrent or metastatic setting. Systemic therapy which was completed more than 6 months prior to randomization, if given as part of multimodal treatment for locally advanced disease, is allowed.
4. Have measurable disease based on RECIST 1.1 as determined by the site and confirmed by BICR. As a guidance to the site investigators, tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
5. Subject has adequate organ function defined by the following parameters (all specimens must be collected within 15 days prior to randomization):

   * Hematological: Absolute neutrophil count (ANC) ≥1500/μL, Platelets ≥100,000/μL; Hemoglobin ≥9.0 g/dL or ≥5.6 mmol/L;
   * Renal: Estimated glomerular filtration rate ≥30 mL/min using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation.
   * Hepatic: Total bilirubin ≤1.5 × ULN or direct bilirubin ≤ULN for subjects with total bilirubin levels \>1.5 × ULN, Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤2.5 ULN (if approved by Medical Monitor, ≤5 × ULN for subjects with liver metastases; AST and ALT \>5 to 20 x ULN may be included if asymptomatic).
   * Coagulation: INR, prothrombin time (PT) ≤1.5 × ULN; if subject is receiving anticoagulant therapy, INR or PT- should be within therapeutic range of anticoagulant.
6. For female subjects defined as women of childbearing potential (WOCBP), a negative pregnancy test must be obtained during screening. If a urine test cannot be confirmed as negative, a serum pregnancy test will be required. Women who are surgically sterile or at least 2 years postmenopausal do not require pregnancy testing.
7. Male subjects of childbearing potential must agree to use a condom as an effective method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.
8. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

Exclusion Criteria:

1. Primary tumor location of nasopharynx (any histology).
2. If the pregnancy test is positive. If a urine test cannot be confirmed as negative, a serum pregnancy test will be required.
3. Has received prior therapy with HPV-specific immunotherapy including therapeutic cancer vaccines and cellular immunotherapy. Note: subjects who have received prophylactic HPV vaccines are eligible for enrollment.
4. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD- L2 agent or with an agent directed to another stimulatory or co- inhibitory T cell receptor including but not limited to CTLA-4, OX40, CD137.
5. Has had major surgery, including surgical resection of tumor, within 30 days prior to randomization, and has not fully recovered as assessed by the investigator.
6. Has received radiotherapy prior to randomization outside of the following minimum washout periods, and has not fully recovered as assessed by the investigator:

   * Fractionated radiotherapy, 2 weeks
   * Stereotactic radiosurgery, 1 week
   * Palliative radiation therapy, 1 week
7. Has received a live vaccine within 30 days prior to randomization.

   Examples of live vaccines include, but are not limited to, the following:

   measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed-virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist ® ) or live attenuated vaccines are not allowed within 30 days prior to randomization.
8. Has received immunomodulatory or immunosuppressive agents (e.g., interferons (IFNs), tumor necrosis factor, interleukins, immunoglobulins or other biological response modifiers (granulocyte colony-stimulating factor \[GCSF\] or granulocyte macrophage stimulating factor \[GMCSF\]) within 30 days prior to randomization.
9. Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 30 days prior to randomization. Note: Subjects who entered the follow-up phase of an investigational study may participate as long as it is permitted in that study consent and has been 30 days after the last dose of the

Trial Locations

• Mayo Clinic Arizona, Phoenix, Arizona, United States
• Marin Cancer Care, Greenbrae, California, United States
• University of California, Orange, Orange, California, United States
• Yale University, New Haven, Connecticut, United States
• Mayo Clinic Florida, Jacksonville, Florida, United States
• Florida Cancer Affiliates - Ocala Oncology, Ocala, Florida, United States
• SCRI - Florida Cancer Specialists, Orlando, Florida, United States
• Emory University - Winship Cancer Institute (WCI), Atlanta, Georgia, United States
• University of Kansas, Westwood, Kansas, United States
• University of Kentucky, Lexington, Kentucky, United States
• ...and 10 more locations

Frequently Asked Questions

Related Conditions

• Head and Neck Cancer
• Squamous Cell Carcinoma
• Oropharyngeal Cancer
• Laryngeal Cancer
• Oral Cavity Cancer
• Hypopharyngeal Cancer
• Recurrent Cancer
• Metastatic Cancer
• HPV-Related Cancers
• Immunotherapy

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