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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and feasibility of a new treatment called MEDI0562, an experimental therapy for individuals with advanced head and neck cancer or melanoma, a type of skin cancer. Researchers aim to understand how this treatment might work before surgery. Participants are divided into two groups: one receives a lower dose of the treatment over several days, while the other receives a higher dose at once before surgery. This trial may suit individuals with advanced forms of these cancers who are eligible for surgical removal of the cancer. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

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.

Is there any evidence suggesting that MEDI0562 is likely to be safe for humans?

Research has shown that MEDI0562 has been tested in people before, with promising results for its safety. In these studies, patients who had already tried other treatments safely received doses up to 10 mg/kg. Most patients tolerated it well, experiencing no severe side effects. While some expected effects of the drug appeared, serious side effects were uncommon. This suggests that MEDI0562 might be safe for individuals with advanced solid tumors, such as head and neck cancer or melanoma. However, since this trial remains in an early stage, it primarily aims to confirm safety and assess how well patients can tolerate the treatment. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about MEDI0562 for head and neck cancer and melanoma because it offers a new mechanism of action by targeting the OX40 receptor, which is different from the traditional chemotherapy and immunotherapy treatments. Unlike standard therapies that often take weeks to show effectiveness, MEDI0562 has the potential to show results rapidly, as it is administered over just a few days before surgical resection. Additionally, the two dosing regimens being tested may provide insights into optimizing the balance between efficacy and safety, potentially leading to more personalized treatment options for patients.

What evidence suggests that MEDI0562 might be an effective treatment for head and neck cancer and melanoma?

Research shows that MEDI0562 is a drug that helps the immune system fight cancer. This trial will test MEDI0562 in two cohorts: one will receive a 30mg dose on days 1, 3, and 5, and the other will receive a 90mg dose on day 1, both followed by surgical resection on day 15. Although specific data on MEDI0562 for head and neck cancer or melanoma is lacking, similar drugs have shown promise in boosting the body's immune response. Studies with similar drugs have demonstrated better immune activity against various solid tumors. Early results suggest that targeting a part of the immune system called OX40 might help prevent cancer recurrence and enhance treatment effectiveness. This approach is being tested to see if it can improve outcomes for patients with these cancers. ^{1 3 6 7 8}

Who Is on the Research Team?

Brenden Curti, MD

Principal Investigator

Providence Health & Services

Are You a Good Fit for This Trial?

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

Ability to give informed consent and comply with the protocol

You are expected to live for more than 12 weeks.

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.

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03336606

Study of MEDI0562 Prior to Surgical Resection in Head ... Cancer-related clinical outcomes in patients receiving MEDI0562 will be compared with historical controls for overall survival. 5 years. Incidence of Treatment- ...

2. withpower.com withpower.com/trial/phase-1-squamous-cell-carcinoma-of-head-and-neck-6-2018-30c48

MEDI0562 for Head and Neck Cancer and Melanoma 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 ...

3. aacrjournals.org aacrjournals.org/clincancerres/article/26/20/5358/82745/Safety-and-Clinical-Activity-of-MEDI0562-a

Safety and Clinical Activity of MEDI0562, a Humanized OX40 ... Immune checkpoint blockade has demonstrated clinical benefits across multiple solid tumor types; however, resistance and relapse often occur.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8532308/

outcome and predictors in a population-based cohort study To evaluate predictive clinico-pathological characteristics on outcome in head and neck melanoma (HNM) in a population-based study with ...

5. researchgate.net researchgate.net/publication/343667366_Safety_and_Clinical_Activity_of_MEDI0562_a_Humanized_OX40_Agonist_Monoclonal_Antibody_in_Adult_Patients_with_Advanced_Solid_Tumors

Safety and Clinical Activity of MEDI0562, a Humanized ... Results In total, 55 patients received ≥1 dose of MEDI0562 and were included in the analysis. The most common tumor type was squamous cell ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/32816951/

Safety and Clinical Activity of MEDI0562, a Humanized ... MEDI0562 was safely administered at doses up to 10 mg/kg in heavily pretreated patients. On-target pharmacodynamic effects were suggested in ...

7. mycancergenome.org mycancergenome.org/content/clinical_trials/NCT03336606/

Clinical Trial: NCT03336606 This clinical trial will evaluate the safety and feasibility of a humanized OX40 agonist, MEDI0562, in the pre-operative setting for patients ...

8. annalsofoncology.org annalsofoncology.org/article/S0923-7534(19)49609-9/fulltext

Safety and clinical activity of MEDI0562, a humanized ... MEDI0562 was generally well tolerated in adult pts with advanced solid tumors and exhibited clinical and pharmacological activity.