Autophagosome Vaccine + Immunotherapy for Head and Neck Cancer

Overseen By George Morris

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Providence Health & Services

Must not be taking: Antibiotics, Immunosuppressants

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

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

Compensation: Varies

Number of Visits: 26

Duration: 12 weeks

56 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments for individuals with recurrent or metastatic head and neck cancer. The study aims to determine how a vaccine (DPV-001, also known as the DRibble vaccine) works with other cancer-fighting drugs to block proteins that promote cancer growth. Suitable candidates for this trial have head and neck cancer that has returned or spread to other body parts. Participants must be able to perform daily activities without significant difficulty. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment combination.

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.

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

Research has shown that DPV-001, a cancer vaccine, yields promising results for head and neck cancer patients. Early findings suggest it can enhance treatment response and slow cancer growth when combined with other therapies. Studies indicate that patients generally tolerate DPV-001 well, with no unexpected side effects.

For INCAGN01876, a drug that boosts the immune system, research indicates it is mostly safe when used with other immune therapies. Fatigue is a common side effect, but it is usually manageable.

INCMGA00012, also known as retifanlimab, is a PD-1 blocker that aids the immune system in fighting cancer. It has been used in other cancer treatments and is generally well-tolerated, with side effects similar to other drugs in its category.

Overall, while each treatment may have side effects, studies suggest they are manageable. This indicates these treatments are reasonably safe for further clinical testing. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they offer a fresh approach to tackling head and neck cancer. Unlike standard treatments that often include surgery, radiation, and chemotherapy, these investigational therapies use an autophagosome vaccine and immunotherapy combinations. DPV-001 is notable for its use of an autophagosome vaccine, which aims to trigger a more robust immune response against cancer cells. Additionally, INCAGN01876 targets the GITR protein to enhance the body's immune response, while INCMGA00012 focuses on blocking the PD-1 pathway to prevent cancer cells from evading immune detection. Together, these treatments could offer a more targeted and potentially more effective way to combat this challenging cancer type.

What evidence suggests that this trial's treatments could be effective for head and neck cancer?

Research has shown that the DPV-001 vaccine can significantly improve outcomes for head and neck cancer patients. In this trial, some participants will receive DPV-001 with a PD-1 blocker, INCMGA00012. Studies have found that this combination triples the rate of positive response and extends the time patients live without cancer progression, compared to using the PD-1 treatment alone.

For the GITR agonist, INCAGN01876, another treatment option in this trial, evidence suggests it can enhance the immune system by boosting certain immune cells, potentially increasing its effectiveness when combined with other immune therapies.

Meanwhile, studies have shown that INCMGA00012, a PD-1 blocker, significantly reduces the risk of cancer progression when combined with traditional chemotherapy. This combination aims to help the body fight cancer cells more effectively. Overall, these treatments show promise in improving cancer treatment outcomes. ^{2 3 6 7 8}

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• DPV-001
• INCAGN01876
• INCMGA00012

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. firstwordpharma.com firstwordpharma.com/story/5910699

Promising Phase Ib Data for UbiVac's DPV-001 in ... UbiVac's DPV-001 Dark Matter combo Immunotherapy triples response rate and progression-free survival over PD-1 alone for patients with r/m head and neck cancer.

2. aacrjournals.org aacrjournals.org/cancerres/article/84/7_Supplement/CT112/742293/Abstract-CT112-An-off-the-shelf-multivalent

Abstract CT112: An off-the-shelf multivalent vaccine ... An off-the-shelf multivalent vaccine containing cancer's dark matter, DPV-001, combined with PD-1 +/- GITR in head & neck cancer: safety, efficacy, and ...

3. jitc.bmj.com jitc.bmj.com/content/12/Suppl_3/A1711

1481 Off-the-shelf dark matter immunotherapy in head & ... DPV-001 is an off-the-shelf biologic containing proteins that are overexpressed by adenocarcinoma and squamous cell cancers.

4. onclive.com onclive.com/view/dr-leidner-on-the-multivalent-vaccine-dpv-001-in-advanced-or-metastatic-hnscc

Dr Leidner on the Multivalent Vaccine DPV-001 ... - OncLive Preclinical studies showed increased therapeutic efficacy when DPV-001 was combined with anti–PD-1 and anti-GITR therapies, informing the ...

5. ubivac.com ubivac.com/

UbiVac November 8th 2024 UbiVac reported that combination immunotherapy with DPV-001 tripled response rates and duration of response over standard treatment with anti- ...

6. ubivac.com ubivac.com/ubivac

Overview — UbiVac UbiVac believes that the early clinical data showing a tripling or more increase in the response rate of patients with HNSCC receiving DPV-001 combination ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT04470024

Study Details | NCT04470024 | Phase Ib Trial of Multivalent ... 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 ...

8. delta.larvol.com delta.larvol.com/Products/?ProductId=a03e5316-3269-4929-817e-d6d570ab068b

DPV-001 / UbiVac UbiVac's lead clinical-stage immunotherapy, DPV-001, was first evaluated as adjuvant therapy for non-small cell lung cancer in an NCI-funded trial.