PDS0101 Vaccine + Pembrolizumab for Oropharyngeal Cancer
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: Mayo Clinic
Must not be taking: Immunosuppressants, Chemotherapy
Disqualifiers: Autoimmune disease, Prior head/neck therapy, others
No Placebo Group
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This phase I/II trial studies how well PDS0101 alone or in combination with pembrolizumab works to shrink tumor in patients with human papillomavirus-associated oropharynx cancer that has spread to nearby tissue or lymph nodes (locally advanced). PDS0101 is a vaccine made from specific peptides that may help the body build an effective immune response to kill tumor cells. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving PDS0101 with or without pembrolizumab may kill more tumor cells in patients with locally advanced human papillomavirus-associated oropharynx cancer before surgery so that it may make the tumor smaller and may reduce the amount of normal tissue that needs to be removed.
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.
What data supports the effectiveness of the PDS0101 Vaccine + Pembrolizumab treatment for oropharyngeal cancer?
Research shows that combining HPV-targeted vaccines with immune checkpoint inhibitors like pembrolizumab can enhance the immune response against HPV-related cancers, leading to tumor regression in preclinical models. Additionally, similar combination treatments have shown promising results in clinical trials for HPV-positive head and neck cancers, improving survival rates and response rates.
12345Is the PDS0101 vaccine safe for humans?
The PDS0101 vaccine has been shown to be safe in a phase I study, with participants experiencing only mild reactions at the injection site and demonstrating positive immune responses.
12678What makes the PDS0101 Vaccine + Pembrolizumab treatment unique for oropharyngeal cancer?
The PDS0101 Vaccine + Pembrolizumab treatment is unique because it combines a vaccine targeting HPV-16 proteins with an immune checkpoint inhibitor, which helps the immune system recognize and attack cancer cells more effectively. This combination aims to enhance the body's immune response against HPV-related oropharyngeal cancer, potentially improving outcomes compared to standard treatments.
24579Eligibility Criteria
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
+15 more
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.
+6 more
Trial Timeline
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
Participant Groups
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.
2Treatment groups
Experimental Treatment
Group I: Arm B (PDS0101, pembrolizumab)Experimental Treatment6 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 Treatment5 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.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Mayo Clinic in RochesterRochester, MN
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Who Is Running the Clinical Trial?
Mayo ClinicLead Sponsor
National Cancer Institute (NCI)Collaborator
References
Human papillomavirus genotype 16 vaccines for cervical cancer prophylaxis and treatment. [2019]More than 11% of the global cancer incidence in females is due to human papillomavirus (HPV) infections, with HPV genotype 16 the most prevalent viral type to infect the cervix. Vaccine strategies currently target HPV 16 genes E6 and E7, constitutively expressed in cervical cancer cells, and L1 and L2, HPV surface antigens. Recent developments in HPV vaccine research are reviewed. Most studies focus on vaccine models showing improved immunogenicity or dual induction of both humeral and cellular systems. Preclinical studies show that (1) L1 /E7 chimeric viral-like proteins induce both neutralizing L1 antibodies and E7-specific T cells; (2) rerouting a cytosolic tumor antigen into the endosomal/lysosomal compartment can improve the therapeutic potency of DNA vaccines; and (3) accelerated E7 protein degradation leads to enhanced antigen presentation in the context of major histocompatability complex class I. Clinical studies show that (1) HPV 16 E7 peptide vaccination can be safely delivered to patients with terminal disease; and (2) HPV-16 capsid proteins harbor at least one HLA-A*201 restricted cytotoxic T lymphocyte (CTL) epitope.
Mucosal HPV E6/E7 Peptide Vaccination in Combination with Immune Checkpoint Modulation Induces Regression of HPV+ Oral Cancers. [2020]High-risk human papillomavirus (HPV)-associated squamous cell carcinomas of the oropharynx (SCCOP) are among the fastest growing cancers. After standard-of-care treatment, however, patients with HPV+ SCCOP have better overall and disease-specific survival than patients with HPV- SCCOP, suggesting the importance of HPV-specific immunity. We reasoned that therapeutic vaccination targeting the HPV-16 E6 and E7 oncogenes could elicit high-affinity, high-frequency tumor antigen-specific T-cell responses, which could then be augmented and shielded from suppression in the tumor microenvironment by immune checkpoint modulation. In this study, we used a preclinical syngeneic mouse model of oral cancer comprised of mouse tonsil-derived epithelial cells stably expressing HPV-16 E6 and E7 genes along with H-ras oncogene (mEER) to identify combinations of vaccination and checkpoint antibodies capable of promoting tumor regression. Intranasal HPV E6/E7 peptide vaccination and single checkpoint antibodies failed to elicit responses in more than half of animals; however, 4-1BB agonist antibody along with either CD40 agonist antibody or CTLA-4 blockade eliminated the majority of established mEER tumors. The combination of intranasal HPV peptide vaccine and α4-1BB and αCTLA-4 antibodies produced curative efficacy and a better safety profile against orally implanted mEER tumors. Correlates of protective immunity included enhanced intratumoral levels of CD8 T cells relative to immunosuppressive regulatory T cells and myeloid-derived suppressor cells. Overall, our results demonstrate combination vaccine-immunotherapy modalities as novel treatment options for HPV+ SCCOP.Significance: Combinations of vaccine and checkpoint modulation are effective and safe treatment options for HPV+ oral cancers. Cancer Res; 78(18); 5327-39. ©2018 AACR.
Vaccine-Based Immunotherapy for Head and Neck Cancers. [2021]In 2019, the FDA approved pembrolizumab, a monoclonal antibody targeting PD-1, for the first-line treatment of recurrent or metastatic head and neck cancers, despite only a limited number of patients benefiting from the treatment. Promising effects of therapeutic vaccination led the FDA to approve the use of the first therapeutic vaccine in prostate cancer in 2010. Research in the field of therapeutic vaccination, including possible synergistic effects with anti-PD(L)1 treatments, is evolving each year, and many vaccines are in pre-clinical and clinical studies. The aim of this review article is to discuss vaccines as a new therapeutic strategy, particularly in the field of head and neck cancers. Different vaccination technologies are discussed, as well as the results of the first clinical trials in HPV-positive, HPV-negative, and EBV-induced head and neck cancers.
Combination immunotherapy with synthetic long peptides and chemotherapy or PD-1 blocker for cancers caused by human papilloma virus type 16. [2023]Therapeutic vaccination of premalignant conditions and of different stages of cancer can be accomplished with several platforms including DNA vaccines, RNA vaccines, synthetic long peptides (SLP), and recombinant viruses. We successfully used a therapeutic vaccine composed of SLP covering the complete sequence of the two oncogenic proteins E6 and E7 of human papillomavirus type 16 (HPV16) as monotherapy in patients with premalignant disease. However, combination treatment might be required in patients with (advanced) cancer because of the hostile cancer microenvironment for T cells in established HPV16+ cancer, often associated with systemic immunosuppression. In patients with late-stage recurrent or metastatic HPV16+ cancers, we have therefore combined treatment with the SLP vaccine, called ISA101b, with either standard-of-care chemotherapy or with immune checkpoint inhibition with anti-PD-1 monoclonal antibody. A strong vaccine-induced interferon gamma-producing T cell response to HPV16 E6/E7 was associated with significantly better survival. In a second phase 1/2 study, patients with recurrent or metastatic HPV16+ oropharyngeal cancer were treated with the combination of ISA101b and anti-PD-1 (nivolumab). In this trial, the clinical overall response rate (ORR) in 22 patients was 36%, twice the ORR in the nivolumab registration trial for this category of patients, and 2/22 patients had a complete clinical response that is ongoing after 4 1/2 years. Other promising strategies for late-stage cancer recipients are the infusion of expanded tumor-infiltrating lymphocytes or the infusion of T cell receptor transduced T cells, both directed against HPV16.
Safety and Efficacy of MEDI0457 plus Durvalumab in Patients with Human Papillomavirus-Associated Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma. [2023]Tumoral programmed cell death ligand-1 (PD-L1) expression is common in human papillomavirus (HPV)-associated head and neck squamous cell carcinoma (HNSCC). We assessed whether a DNA vaccine targeting HPV-16/18 E6/E7 with IL12 adjuvant (MEDI0457) combined with the PD-L1 inhibitor durvalumab could enhance HPV-specific T-cell response and improve outcomes in recurrent/metastatic HPV-16/18-associated HNSCC.
First-in-Human Phase I Clinical Trial of an SFV-Based RNA Replicon Cancer Vaccine against HPV-Induced Cancers. [2022]A first-in-human phase I trial of Vvax001, an alphavirus-based therapeutic cancer vaccine against human papillomavirus (HPV)-induced cancers was performed assessing immunological activity, safety, and tolerability. Vvax001 consists of replication-incompetent Semliki Forest virus replicon particles encoding HPV16-derived antigens E6 and E7. Twelve participants with a history of cervical intraepithelial neoplasia were included. Four cohorts of three participants were treated per dose level, ranging from 5 × 105 to 2.5 × 108 infectious particles per immunization. The participants received three immunizations with a 3-week interval. For immune monitoring, blood was drawn before immunization and 1 week after the second and third immunization. Immunization with Vvax001 was safe and well tolerated, with only mild injection site reactions, and resulted in both CD4+ and CD8+ T cell responses against E6 and E7 antigens. Even the lowest dose of 5 × 105 infectious particles elicited E6/E7-specific interferon (IFN)-γ responses in all three participants in this cohort. Overall, immunization resulted in positive vaccine-induced immune responses in 12 of 12 participants in one or more assays performed. In conclusion, Vvax001 was safe and induced immune responses in all participants. These data strongly support further clinical evaluation of Vvax001 as a therapeutic vaccine in patients with HPV-related malignancies.
ISA101 and nivolumab for HPV-16+ cancer: updated clinical efficacy and immune correlates of response. [2023]Label="BACKGROUND">The combination of ISA101, a human papilloma virus (HPV) 16 peptide vaccine, and nivolumab showed a promising response rate of 33% in patients with incurable HPV-16+ cancer. Here we report long-term clinical outcomes and immune correlates of response.
Immunomodulation to enhance the efficacy of an HPV therapeutic vaccine. [2021]Label="BACKGROUND">While prophylactic human papillomavirus (HPV) vaccines will certainly reduce the incidence of HPV-associated cancers, these malignancies remain a major health issue. PDS0101 is a liposomal-based HPV therapeutic vaccine consisting of the immune activating cationic lipid R-DOTAP and HLA-unrestricted HPV16 peptides that has shown in vivo CD8+ T cell induction and safety in a phase I study. In this report, we have employed the PDS0101 vaccine with two immune modulators previously characterized in preclinical studies and which are currently in phase II clinical trials. Bintrafusp alfa (M7824) is a first-in-class bifunctional fusion protein composed of the extracellular domains of the transforming growth factor-β receptor type II (TGFβRII) fused to a human IgG1 monoclonal antibody blocking programmed cell death protein-1 ligand (PDL1), designed both as a checkpoint inhibitor and to bring the TGFβRII 'trap' to the tumor microenvironment (TME). NHS-interleukin-12 (NHS-IL12) is a tumor targeting immunocytokine designed to bring IL-12 to the TME and thus enhance the inflammatory Th1 response.
Phase Ib/II trial of tipapkinogene sovacivec, a therapeutic human papillomavirus16-vaccine, in combination with avelumab in patients with advanced human papillomavirus16-positive cancers. [2023]To evaluate tipapkinogene sovacivec (TG4001), a viral immunotherapeutic vaccine expressing human papillomavirus (HPV)16 E6/E7 non-oncogenic proteins and IL-2, in combination with avelumab in HPV16+ cancer patients.