Autophagosome Vaccine + Immunotherapy for Head and Neck Cancer

Recruiting in Palo Alto (17 mi)

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Providence Health & Services

Must not be taking: Antibiotics, Immunosuppressants

Disqualifiers: Organ transplant, Active infection, Autoimmune disease, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This is a phase Ib study with a safety lead-in (n = 6 per arm) evaluating combinatorial DPV-001 + sequenced PD-1 blockade, with or without GITR agonist, in recurrent or metastatic HNSCC.

Do I need to stop taking my current medications for this trial?

The trial does not specify if you need to stop taking your current medications, but you cannot be on any concurrent chemotherapy, investigational agents, or hormonal therapy for cancer treatment. Hormonal therapy for non-cancer conditions is allowed.

What data supports the effectiveness of the treatment Autophagosome Vaccine + Immunotherapy for Head and Neck Cancer?

Research shows that inhibitors of PD-1 and PD-L1, which are part of the treatment, have been used in head and neck cancer therapy and reported to improve outcomes with an acceptable safety profile. Additionally, vaccine-based approaches are being explored as a new strategy for head and neck cancers, although success has been limited so far. ^{1 2 3 4 5}

What makes the Autophagosome Vaccine + Immunotherapy treatment unique for head and neck cancer?

This treatment is unique because it uses tumor-derived autophagosomes (DRibbles) to enhance the immune response by efficiently presenting tumor antigens to activate T cells, which is a novel approach compared to traditional therapies. The combination with immunotherapy agents like Ragifilimab and Retifanlimab aims to further boost the body's immune system to fight cancer. ^{6 7 8 9 10}

Research Team

Eligibility Criteria

Adults with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) who are in relatively good health, as indicated by ECOG performance status of 0-2. They must have adequate organ function, no major surgeries within the last month, not be on high-dose steroids for autoimmune diseases, and cannot be pregnant or fathering a child without using contraception. HIV-positive patients can join if they're stable on antiretroviral therapy.

Inclusion Criteria

My kidneys work well enough to clear waste from my blood.

Laboratory values:

Negative bHCG (urine/serum) Women of childbearing potential only

Exclusion Criteria

I have nerve damage that affects my daily activities.

I have taken short-term steroids for allergies or as premedication for treatments.

I haven't had major surgery in the last 28 days, except for minor procedures to relieve symptoms.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive combination therapy with DPV-001 with or without anti-GITR, followed by delayed anti-PD-1. Mandatory biopsy at week 2, restaging CT and biopsy at 8 weeks, confirmatory CT at 12 weeks.

12 weeks

Biopsy at week 2, CT at weeks 8 and 12

Follow-up

Participants are monitored for safety and effectiveness after treatment. Restaging CT at week 24 and every 12 weeks thereafter.

90 days after last treatment

CT at week 24 and every 12 weeks

Long-term follow-up

Overall survival is assessed from the start of combination until death due to any cause.

Up to 2 years

Treatment Details

Interventions

• DPV-001 (Cancer Vaccine)
• INCAGN01876 (PD-1 Inhibitor)
• INCMGA00012 (PD-1 Inhibitor)

Trial Overview The trial is testing a new cancer vaccine called DPV-001 combined with an anti-PD-1 immunotherapy drug named INCMGA00012. Some participants will also receive INCAGN01876, which activates immune cells via GITR to see if it enhances treatment effects against HNSCC. The study has two arms comparing these treatments.

Participant Groups

Group I: Arm 2 (CLOSED TO ENROLLMENT) Experimental Treatment 3 Interventions

Vax + anti-GITR + delayed anti-PD-1

Group II: Arm 1 Experimental Treatment 2 Interventions

Vax + delayed anti-PD-1

Who Is Running the Clinical Trial?

Providence Health & Services

Lead Sponsor

Trials

131

Recruited

827,000+

Dr. Laurel Soot

Providence Health & Services

Chief Medical Officer since 2024

MD, FACS

Erik Wexler

Providence Health & Services

Chief Executive Officer

Bachelor's degree in Business Administration from the University of Massachusetts Amherst

Findings from Research

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]

PD-1 inhibitors significantly improve overall survival in patients with recurrent or metastatic head and neck cancer compared to standard treatments, with a relative risk of death reduced by 40%.

Patients with human papillomavirus (HPV) positive head and neck cancer showed better response rates to PD-1/PD-L1 inhibitors than those who are HPV negative, indicating that HPV status may influence treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects and safety of PD-1/PD-L1 inhibitors on head and neck cancer: A systematic review and meta-analysis. Wang, BC., Cao, RB., Li, PD., et al.[2021]

In the phase II HAWK study involving 112 patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) who had high PD-L1 expression, durvalumab showed an objective response rate of 16.2%, with a notably higher rate of 29.4% in HPV-positive patients.

Durvalumab was found to have an acceptable safety profile, with 57.1% of patients experiencing treatment-related adverse events, but none were fatal, indicating it could be a viable treatment option for this difficult-to-treat patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab for recurrent or metastatic head and neck squamous cell carcinoma: Results from a single-arm, phase II study in patients with ≥25% tumour cell PD-L1 expression who have progressed on platinum-based chemotherapy. Zandberg, DP., Algazi, AP., Jimeno, A., et al.[2020]

In the phase III KESTREL study, durvalumab, with or without tremelimumab, did not show superior overall survival compared to the EXTREME regimen in patients with PD-L1-high head and neck squamous cell carcinoma, with median survival times being similar (around 10.9 months).

However, durvalumab treatments resulted in a higher percentage of patients maintaining a response at 12 months (49.3% and 48.1%) and had significantly fewer severe treatment-related adverse events (8.9% for durvalumab and 19.1% for durvalumab plus tremelimumab) compared to the EXTREME regimen (53.1%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab with or without tremelimumab versus the EXTREME regimen as first-line treatment for recurrent or metastatic squamous cell carcinoma of the head and neck: KESTREL, a randomized, open-label, phase III study. Psyrri, A., Fayette, J., Harrington, K., et al.[2023]

Vaccine-based treatments for advanced squamous cell carcinoma of the head and neck have shown limited success, highlighting the need for a deeper understanding of what factors contribute to their effectiveness or failure.

The review suggests that analyzing existing vaccine strategies can help identify new directions for research that may improve disease control and survival outcomes in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vaccine-based approaches to squamous cell carcinoma of the head and neck. Zhang, X., Moche, JA., Farber, D., et al.[2007]

Tumor-derived autophagosomes (DRibbles) can effectively activate and proliferate human B cells, leading to the production of important immune signaling molecules like chemokines and cytokines.

The activation of human B cells by DRibbles is significantly influenced by the presence of membrane-bound high-mobility group B1 (HMGB1), highlighting its potential role in developing B-DRibbles vaccines for cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tumor-Derived Autophagosomes (DRibbles) Activate Human B Cells to Induce Efficient Antigen-Specific Human Memory T-Cell Responses. Ren, H., Zhang, T., Wang, Y., et al.[2021]

A novel cancer vaccine platform using tumor cell-derived autophagosomes (DRibbles) was developed and tested in mouse models, showing promising results in inducing anti-tumor immunity against hepatocellular carcinoma (HCC).

Immunization with DRibbles-pulsed dendritic cells significantly inhibited tumor growth in both BALB/c mouse HCC models and humanized mouse models, suggesting potential for this therapy in treating residual tumors after primary HCC treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-tumor efficacy of a hepatocellular carcinoma vaccine based on dendritic cells combined with tumor-derived autophagosomes in murine models. Su, S., Zhou, H., Xue, M., et al.[2022]

The DRibble vaccine, derived from tumor cells, effectively enhances the cross-presentation of tumor antigens to CD8(+) T cells, utilizing autophagosomes to carry both long-lived and short-lived proteins, which is crucial for its function as a cancer immunotherapy.

In preclinical models, the DRibble vaccine demonstrated significant antitumor efficacy, successfully eradicating 3LL Lewis lung tumors and delaying the growth of B16F10 melanoma, indicating its potential for further clinical testing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tumor-derived autophagosome vaccine: mechanism of cross-presentation and therapeutic efficacy. Li, Y., Wang, LX., Pang, P., et al.[2022]

The study demonstrated that dendritic cells loaded with tumor-derived autophagosomes (DRibbles) can effectively stimulate T cell responses, leading to significant antitumor effects in mice, indicating their potential as a cancer vaccine.

DRibble-DCs showed superior antitumor efficacy compared to other treatments, such as DRibbles alone or tumor cell lysate-loaded dendritic cells, while also affecting endoplasmic reticulum stress pathways, suggesting a complex mechanism of action.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunocompetence and mechanism of the DRibble-DCs vaccine for oral squamous cell carcinoma. Dong, H., Su, H., Chen, L., et al.[2022]

The Chinese herbal formula Qing Yan Li Ge Tang (QYLGT) effectively inhibits cell viability and colony formation in nasopharyngeal carcinoma (NPC) cells, suggesting its potential as a therapeutic agent.

QYLGT induces autophagic cell death in NPC cells through the activation of the PI3K/Akt/mTOR pathway, while not significantly inducing apoptosis, indicating a unique mechanism of action for its anticancer effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Qing Yan Li Ge Tang, a Chinese Herbal Formula, Induces Autophagic Cell Death through the PI3K/Akt/mTOR Pathway in Nasopharyngeal Carcinoma Cells In Vitro. Yang, CH., Tung, KL., Wu, YT., et al.[2021]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Vaccine-Based Immunotherapy for Head and Neck Cancers. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

The effects and safety of PD-1/PD-L1 inhibitors on head and neck cancer: A systematic review and meta-analysis. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Durvalumab for recurrent or metastatic head and neck squamous cell carcinoma: Results from a single-arm, phase II study in patients with ≥25% tumour cell PD-L1 expression who have progressed on platinum-based chemotherapy. [2020]

4. England pubmed.ncbi.nlm.nih.gov

Durvalumab with or without tremelimumab versus the EXTREME regimen as first-line treatment for recurrent or metastatic squamous cell carcinoma of the head and neck: KESTREL, a randomized, open-label, phase III study. [2023]

5. Denmark pubmed.ncbi.nlm.nih.gov

Vaccine-based approaches to squamous cell carcinoma of the head and neck. [2007]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Tumor-Derived Autophagosomes (DRibbles) Activate Human B Cells to Induce Efficient Antigen-Specific Human Memory T-Cell Responses. [2021]

7. Thailand pubmed.ncbi.nlm.nih.gov

Anti-tumor efficacy of a hepatocellular carcinoma vaccine based on dendritic cells combined with tumor-derived autophagosomes in murine models. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Tumor-derived autophagosome vaccine: mechanism of cross-presentation and therapeutic efficacy. [2022]

9. New Zealand pubmed.ncbi.nlm.nih.gov

Immunocompetence and mechanism of the DRibble-DCs vaccine for oral squamous cell carcinoma. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Qing Yan Li Ge Tang, a Chinese Herbal Formula, Induces Autophagic Cell Death through the PI3K/Akt/mTOR Pathway in Nasopharyngeal Carcinoma Cells In Vitro. [2021]