PDS0101 Vaccine + Pembrolizumab for Oropharyngeal Cancer

Overseen By Clinical Trials Referral Office

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Mayo Clinic

Must not be taking: Immunosuppressants, Chemotherapy

Disqualifiers: Autoimmune disease, Prior head/neck therapy, others

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

Compensation: Varies

Number of Visits: 6

Duration: 6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of a new cancer vaccine, PDS0101, alone or combined with the immunotherapy drug pembrolizumab, in shrinking tumors in individuals with HPV-related throat cancer. The goal is to enhance the body's immune response to reduce the cancer's size before surgery, facilitating removal while preserving healthy tissue. Individuals with HPV-associated oropharyngeal cancer that has spread to nearby tissues or lymph nodes may be suitable candidates, particularly if they plan to undergo surgery or chemo-radiation. As a Phase 1, Phase 2 trial, this research seeks to understand the treatment's effects and measure its effectiveness in an initial, smaller group, offering participants an opportunity to contribute to groundbreaking cancer treatment advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on immunosuppressive medication, you must stop at least 14 days before joining the trial, unless it's a low-dose steroid or certain other exceptions.

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

Research has shown that PDS0101, a vaccine targeting HPV, has a good safety record. In earlier studies, patients tolerated PDS0101 well, experiencing only a few side effects. The treatment helps the immune system fight cancer cells.

When combined with pembrolizumab, a drug that aids the immune system in attacking cancer, PDS0101 maintains positive safety results. Previous studies on this combination reported manageable side effects, suggesting the treatment is generally safe for patients.

These trials are in the early stages, so researchers are still assessing the treatments' safety for people. However, since the FDA has already approved pembrolizumab for other cancers, this adds some confidence in its safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for oropharyngeal cancer because they offer innovative approaches compared to traditional options like surgery, radiation, and chemotherapy. PDS0101 is a liposomal vaccine targeting the HPV-16 E6/E7 proteins, which are often involved in oropharyngeal cancers. This approach aims to stimulate the immune system to specifically attack cancer cells. Pembrolizumab, a well-known immunotherapy, enhances this effect by blocking the PD-1 pathway, helping the immune system recognize and destroy cancer cells more effectively. Together, these treatments have the potential to provide a targeted and robust immune response, which could improve outcomes and reduce side effects compared to conventional treatments.

What evidence suggests that this trial's treatments could be effective for oropharyngeal cancer?

Research has shown that the PDS0101 vaccine may help the body fight HPV-related cancers. In earlier studies, PDS0101 alone helped create special immune cells that target cancer cells in throat cancer models. In this trial, some participants will receive PDS0101 alone. Another study found that when PDS0101 was used with pembrolizumab, patients with HPV16-related head and neck cancers lived for more than 39 months on average. In this trial, other participants will receive the combination of PDS0101 and pembrolizumab. These findings suggest that PDS0101, whether used alone or with pembrolizumab, could effectively target and reduce HPV-related throat tumors, potentially shrinking tumors and improving outcomes for patients with this type of cancer. ^{1 3 5 6 7}

Who Is on the Research Team?

David M. Routman, M.D.

Principal Investigator

Mayo Clinic in Rochester

Are You a Good Fit for This Trial?

Adults over 18 with locally advanced HPV-associated oropharynx cancer, who have not received certain treatments recently and do not have active autoimmune diseases, other cancers within the last 2 years (with some exceptions), or uncontrolled illnesses. Participants must be able to undergo surgery and agree to use contraception if applicable.

Inclusion Criteria

Platelet count >= 75,000/mm^3

Hemoglobin >= 9.0 g/dL

Prothrombin time (PT)/international normalized ratio (INR)/partial thromboplastin time (PTT) =< 1.5 X ULN

Exclusion Criteria

I haven't had a stroke, heart issues, blood clots, or taken immune system drugs recently.

I have not had any other cancer within the last 2 years.

I am currently using or have used immunosuppressive medication.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive PDS0101 alone or in combination with pembrolizumab every 21 days for up to 2 cycles

6 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

Up to 2 years

Every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• Liposomal HPV-16 E6/E7 Multipeptide Vaccine PDS0101
• Pembrolizumab

Trial Overview The trial is testing a vaccine called PDS0101 alone or combined with pembrolizumab, an immunotherapy drug. It aims to see if these treatments can shrink tumors before surgery in patients with HPV-related throat cancer. The study will assess how well the body's immune system responds to destroy tumor cells.

How Is the Trial Designed?

Group I: Arm B (PDS0101, pembrolizumab) Experimental Treatment 6 Interventions

Patients receive PDS0101 SC on day 1 and pembrolizumab intravenously (IV) over 30 minutes on day 1 of each cycle. Treatment repeats every 21 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or FDG-PET/CT and blood sample collection throughout the trial. Patients may undergo a biopsy during screening and on the trial.

Group II: Arm A (PDS0101) Experimental Treatment 5 Interventions

Patients receive PDS0101 SC on day 1 of each cycle. Treatment repeats every 21 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or FDG-PET/CT and blood sample collection throughout the trial. Patients may undergo a biopsy during screening and on the trial.

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a study of 24 patients with advanced HPV-16+ cancer, the combination of the ISA101 vaccine and nivolumab showed a promising long-term response rate, with 38% of patients remaining progression-free at 3 years and a median duration of response of 11.2 months.

The presence of activated T cells and macrophages in tumors was correlated with better clinical responses, and gene expression analysis indicated that higher levels of immune response and interferon-signaling genes were associated with positive treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ISA101 and nivolumab for HPV-16+ cancer: updated clinical efficacy and immune correlates of response. Sousa, LG., Rajapakshe, K., Rodriguez Canales, J., et al.[2023]

HPV infections, particularly HPV genotype 16, contribute to over 11% of global cancer cases in females, highlighting the importance of effective vaccination strategies targeting HPV genes E6 and E7, as well as surface antigens L1 and L2.

Recent research shows promising developments in HPV vaccines, including the safe delivery of HPV 16 E7 peptide vaccinations to terminal patients and the potential for improved immune responses through innovative vaccine designs that enhance antigen presentation and induce both antibody and T cell responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human papillomavirus genotype 16 vaccines for cervical cancer prophylaxis and treatment. Cornelison, TL.[2019]

A therapeutic vaccine using synthetic long peptides (SLP) targeting HPV16 proteins E6 and E7 showed promising results as a monotherapy for patients with premalignant disease, but combination treatments may be necessary for advanced cancer due to the challenging tumor environment.

In a phase 1/2 study combining the SLP vaccine ISA101b with the anti-PD-1 antibody nivolumab, 36% of patients with recurrent or metastatic HPV16+ oropharyngeal cancer had a clinical response, which is significantly higher than the response rate seen with nivolumab alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination immunotherapy with synthetic long peptides and chemotherapy or PD-1 blocker for cancers caused by human papilloma virus type 16. Melief, CJM., van der Gracht, E., Wiekmeijer, AS.[2023]

In a phase Ib/IIa study involving 35 patients with recurrent/metastatic HPV-16/18-associated head and neck cancer, the combination of the DNA vaccine MEDI0457 and the PD-L1 inhibitor durvalumab showed an objective response rate of 27.6%, indicating some effectiveness in enhancing HPV-specific T-cell responses.

The treatment was generally well tolerated, with 80% of patients experiencing treatment-related adverse events, mostly mild to moderate, and a median overall survival of 29.2 months, suggesting potential clinical benefit despite not meeting the primary efficacy endpoint.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of MEDI0457 plus Durvalumab in Patients with Human Papillomavirus-Associated Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma. Aggarwal, C., Saba, NF., Algazi, A., et al.[2023]

The PDS0101 therapeutic vaccine effectively generated HPV-specific T cells and showed antitumor activity in mouse models of HPV-expressing cancers, indicating its potential as a treatment for HPV-related malignancies.

Combining PDS0101 with NHS-IL12 significantly enhanced antitumor effects and increased T cell activity in the tumor microenvironment, while bintrafusp alfa alone did not show antitumor effects, highlighting the importance of combination therapies in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunomodulation to enhance the efficacy of an HPV therapeutic vaccine. Smalley Rumfield, C., Pellom, ST., Morillon Ii, YM., et al.[2021]

The phase I trial of Vvax001, a therapeutic cancer vaccine targeting HPV-induced cancers, demonstrated safety and tolerability in 12 participants, with only mild injection site reactions reported.

All participants showed positive immune responses, including CD4+ and CD8+ T cell activation against HPV16 antigens, indicating that Vvax001 effectively stimulates the immune system and warrants further clinical evaluation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-in-Human Phase I Clinical Trial of an SFV-Based RNA Replicon Cancer Vaccine against HPV-Induced Cancers. Komdeur, FL., Singh, A., van de Wall, S., et al.[2022]

The combination of tipapkinogene sovacivec (TG4001) and avelumab was found to be safe for HPV16+ cancer patients, with no dose-limiting toxicities reported and most treatment-related adverse events being mild (grade 1/2).

In this study involving 43 heavily pretreated patients, the overall response rate was 22%, with a median overall survival of 11 months, indicating that this treatment can provide antitumor activity even in advanced cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase Ib/II trial of tipapkinogene sovacivec, a therapeutic human papillomavirus16-vaccine, in combination with avelumab in patients with advanced human papillomavirus16-positive cancers. Borcoman, E., Lalanne, A., Delord, JP., et al.[2023]

Pembrolizumab, an FDA-approved monoclonal antibody for recurrent or metastatic head and neck cancers, has shown limited efficacy, highlighting the need for alternative treatments.

Therapeutic vaccination is emerging as a promising strategy in head and neck cancers, with ongoing research into its potential synergistic effects when combined with anti-PD(L)1 therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vaccine-Based Immunotherapy for Head and Neck Cancers. Beyaert, S., Machiels, JP., Schmitz, S.[2021]

Therapeutic vaccination targeting HPV-16 E6 and E7 oncogenes, combined with immune checkpoint modulation, showed promising results in a preclinical mouse model, leading to significant tumor regression in HPV+ squamous cell carcinomas of the oropharynx.

The combination of intranasal HPV peptide vaccination with 4-1BB and CTLA-4 antibodies not only eliminated most established tumors but also demonstrated a better safety profile, enhancing protective immunity by increasing CD8 T cells in the tumor environment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mucosal HPV E6/E7 Peptide Vaccination in Combination with Immune Checkpoint Modulation Induces Regression of HPV+ Oral Cancers. Dorta-Estremera, S., Chin, RL., Sierra, G., et al.[2020]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11843463/

Novel Combination Immunotherapy and Clinical Activity in ... This phase 1/2 nonrandomized clinical trial found the combination of PDS0101, PDS01ADC, and BA has an acceptable safety profile and showed ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05232851

Study Details | NCT05232851 | A Vaccine (PDS0101) ... This phase I/II trial studies how well PDS0101 alone or in combination with pembrolizumab works to shrink tumor in patients with human ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7304848/

Immunomodulation to enhance the efficacy of an HPV ... As a monotherapy, the PDS0101 vaccine generated HPV-specific T cells and antitumor activity in mice bearing HPV-expressing mEER oropharyngeal ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2021.39.15_suppl.2501

Phase II evaluation of the triple combination of PDS0101 ... Results: Fourteen pts with advanced HPV 16+ cancers (5 cervical, 2 vaginal/vulvar, 4 anal, 3 oropharyngeal) were treated. 4/14 (28.6%) pts ...

5. withpower.com withpower.com/trial/phase-2-carcinoma-2-2022-424de

PDS0101 Vaccine + Pembrolizumab for Oropharyngeal Cancer Giving PDS0101 with or without pembrolizumab may kill more tumor cells in patients with locally advanced human papillomavirus-associated oropharynx cancer ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11856027/

Vaccine-Based Immunotherapy for Oropharyngeal and ... Research on vaccine-based immunotherapy for OPC and NPC focuses on targeting viral antigens, particularly HPV E6/E7 and EBV EBNA1/LMP2.

7. researchgate.net researchgate.net/publication/359175933_Preliminary_Safety_of_PDS0101_Versamune_HPVmix_and_Pembrolizumab_Combination_Therapy_in_Subjects_with_RecurrentMetastatic_Human_Papillomavirus-16_Positive_Oropharyngeal_Squamous_Cell_Carcinoma_OPSCC

Preliminary Safety of PDS0101 (Versamune +HPVmix) and ... It has been shown to specifically upregulate type I interferons, allowing generation of high levels of polyfunctional HPV16-specific CD8 and CD4 T cells in vivo ...