MEDI0562 for Head and Neck Cancer and Melanoma

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Providence Health & Services

Must not be taking: Immunosuppressants, Chemotherapy

Disqualifiers: Active infection, Uncontrolled illness, others

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

Compensation: Varies

Number of Visits: 4

Duration: 2 weeks

35 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot take any other cancer treatments while participating, and certain medications like immunosuppressive drugs must be stopped 14 days before starting the trial.

What data supports the effectiveness of the drug MEDI0562 for head and neck cancer and melanoma?

While there is no direct data on MEDI0562, similar drugs like pembrolizumab, which are immune checkpoint inhibitors, have shown promise in treating head and neck cancer by improving survival rates and having a favorable safety profile. These drugs work by helping the immune system recognize and attack cancer cells more effectively. ^{1 2 3 4 5}

Is MEDI0562 safe for treating head and neck cancer and melanoma?

Immune checkpoint inhibitors, like MEDI0562, can cause side effects known as immune-related adverse events (irAEs), which are usually temporary but can sometimes be serious. In some cases, these side effects can affect organs and may be more severe in patients with head and neck cancer. However, with proper management, these side effects can often be resolved. ^{6 7 8 9 10}

What is the purpose of this trial?

This clinical trial will evaluate the safety and feasibility of a humanized OX40 agonist, MEDI0562, in the pre-operative setting for patients with head and neck squamous cell carcinoma or melanoma.

Research Team

Brenden Curti, MD

Principal Investigator

Providence Health & Services

Eligibility Criteria

This trial is for adults with advanced head and neck squamous cell carcinoma or stage IIIb/IIIC melanoma who are candidates for surgery. They must have a life expectancy over 12 weeks, acceptable organ function, no major surgeries within the last 28 days, and not be on immunosuppressive meds recently. Women must test negative for pregnancy and agree to contraception.

Inclusion Criteria

Your white blood cell count, hemoglobin level, platelet count, kidney function, liver enzymes, and blood clotting time must be within certain normal ranges. If you are a woman able to have children, you must have a negative pregnancy test.

Ability to give informed consent and comply with the protocol

You are expected to live for more than 12 weeks.

Exclusion Criteria

Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study

I haven't taken any experimental cancer treatments in the last 28 days.

I am not on any cancer treatments but may be on hormone therapy for other reasons.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive MEDI0562 prior to surgical resection. Cohort I receives 90mg on day 1, and Cohort II receives 30mg on days 1, 3, and 5.

2 weeks

3 visits (in-person) for Cohort II, 1 visit (in-person) for Cohort I

Surgical Resection

Surgical resection is performed approximately on day 15 after MEDI0562 administration.

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety, immune response, and clinical outcomes after treatment and surgery.

5 years

Treatment Details

Interventions

• MEDI0562

Trial Overview The trial studies MEDI0562, an OX40 agonist, in patients before they undergo surgical removal of their cancer. It aims to assess the safety of this drug when given prior to surgery and whether it's feasible as a pre-operative treatment option.

Participant Groups

Group I: Cohort II Active Control 1 Intervention

MEDI0562 administration (30mg on days 1, 3, 5) followed by surgical resection (day 15)

Group II: Cohort I Active Control 1 Intervention

MEDI0562 administration (90mg on day 1) followed by surgical resection (day 15)

Who Is Running the Clinical Trial?

Providence Health & Services

Lead Sponsor

Trials

131

Recruited

827,000+

MedImmune LLC

Industry Sponsor

Trials

348

Recruited

788,000+

Founded

1988

Headquarters

Gaithersburg, USA

Known For

Biologics research

Top Products

Synagis, FluMist

Dr. Reginald Seeto

MedImmune LLC

Chief Medical Officer since 2008

MD from University of Sydney, B.Sc. from University of Sydney

Peter Greenleaf

MedImmune LLC

Chief Executive Officer since 2006

MBA from St. Joseph’s University, B.S. from Western Connecticut State University

Providence Cancer Center, Earle A. Chiles Research Institute

Collaborator

Trials

21

Recruited

500+

Findings from Research

Pembrolizumab, an immune checkpoint inhibitor, has shown significantly improved overall survival in patients with relapsed and/or metastatic head and neck squamous cell carcinoma compared to the standard EXTREME regimen, indicating a promising shift in treatment options.

This review highlights the importance of understanding the mechanisms of immune checkpoint inhibitors, including their interaction with the immune system and the challenges posed by tumor heterogeneity and PD-L1 expression, which are crucial for optimizing patient selection for treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potential of Pembrolizumab in Metastatic or Recurrent Head and Neck Cancer: Evidence to Date. McCusker, MG., Orkoulas-Razis, D., Mehra, R.[2020]

In a study involving 882 participants with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC), pembrolizumab alone significantly improved overall survival compared to cetuximab with chemotherapy, especially in patients with high PD-L1 expression (CPS of 20 or more).

Pembrolizumab combined with chemotherapy also showed improved overall survival compared to cetuximab with chemotherapy across all populations, indicating that pembrolizumab is an effective first-line treatment option for HNSCC, particularly for those with PD-L1 positivity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): a randomised, open-label, phase 3 study. Burtness, B., Harrington, KJ., Greil, R., et al.[2021]

The 22C3 laboratory developed test (LDT) for PD-L1 expression in head and neck squamous cell carcinoma (HNSCC) shows almost perfect concordance with the standardized 22C3 pharmDx assay, indicating it can reliably identify patients who may benefit from pembrolizumab treatment.

Both assays demonstrated substantial interobserver agreement and similar levels of intratumor heterogeneity, confirming that the LDT is a safe and effective alternative to the pharmDx assay for patient selection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inter-assay reliability of programmed cell death-ligand 1 in head and neck squamous cell carcinoma. Hempenius, MA., Bisheshar, SK., Slagter-Menkema, L., et al.[2022]

Pembrolizumab, a PD-1 inhibitor, has shown significant overall response rates and survival benefits in patients with recurrent or metastatic head and neck squamous cell carcinoma compared to chemotherapy alone, particularly in populations with high PD-L1 expression (CPS ≥ 20 and CPS ≥ 1).

The safety profile of pembrolizumab is comparable to other PD-1/PD-L1 inhibitors, with common side effects including diarrhea and hypothyroidism, but it has a favorable toxicity profile compared to the EXTREME chemotherapy regimen, highlighting the importance of PD-L1 scoring for patient selection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety evaluation of pembrolizumab for treating recurrent head and neck squamous cell carcinoma. Desilets, A., Soulières, D.[2022]

In a study of seven patients with recurrent head and neck mucosal melanoma who received immune checkpoint inhibitors (ICIs) after proton beam therapy (PBT), four patients experienced immune-related adverse events (irAEs), indicating a potential increase in risk when combining these treatments.

Despite the increased risk of irAEs, particularly in the irradiation field, the adverse events were manageable and resolved with appropriate treatment, suggesting that a strategy combining PBT and ICIs could be viable for treating advanced melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of immune checkpoint inhibitors after proton beam therapy in head and neck mucosal melanoma: a case series. Uematsu, M., Nakajima, H., Hosono, A., et al.[2023]

References

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

Potential of Pembrolizumab in Metastatic or Recurrent Head and Neck Cancer: Evidence to Date. [2020]

2. Austria pubmed.ncbi.nlm.nih.gov

Immunotherapy for head and neck squamous cell carcinoma. [2021]

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

Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): a randomised, open-label, phase 3 study. [2021]

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

Inter-assay reliability of programmed cell death-ligand 1 in head and neck squamous cell carcinoma. [2022]

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

New developments in the management of head and neck cancer - impact of pembrolizumab. [2022]

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

Immune Checkpoint Inhibitor Toxicity in Head and Neck Cancer: From Identification to Management. [2020]

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

Pharmacogenomic landscape of head and neck squamous cell carcinoma informs precision oncology therapy. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Safety evaluation of pembrolizumab for treating recurrent head and neck squamous cell carcinoma. [2022]

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

Proton beam therapy as a nonsurgical approach to mucosal melanoma of the head and neck: a pilot study. [2018]

10. England pubmed.ncbi.nlm.nih.gov

Safety of immune checkpoint inhibitors after proton beam therapy in head and neck mucosal melanoma: a case series. [2023]