MEDI4736 + AZD9150/AZD5069 for Head & Neck Cancer

No longer recruiting at 49 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: AstraZeneca

Must not be taking: Steroids, Chemotherapy

Disqualifiers: Second malignancy, Autoimmune disease, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests new treatments for head and neck cancer. Researchers aim to evaluate the effectiveness of combining the drugs AZD5069, AZD9150, and MEDI4736 (an immunotherapy drug) against this cancer type. The study explores different combinations to determine optimal dosages and safety. Individuals with head and neck cancer that cannot be treated with surgery or radiation may be suitable candidates, particularly if they have not undergone extensive prior treatments. As a Phase 1 and Phase 2 trial, this research focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you must stop taking your current medications, but you must complete any previous cancer-related treatments before enrolling. There is a washout period (time without taking certain medications) of 21 days or 5 half-lives for chemotherapy before starting the study.

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

Research shows that the combination treatments in this trial—AZD5069 with MEDI4736, and AZD9150 with MEDI4736—are being evaluated for safety and patient tolerance. Studies have found these treatments are generally well-tolerated, though some serious side effects have occurred. For example, some patients experienced serious bleeding when treated with MEDI4736 combined with other drugs.

Early results suggest these drugs, when used together, might enhance tumor-fighting ability. However, safety remains a key focus, so researchers are closely monitoring for negative effects. As this trial is in the early stages, the treatments are still being tested to determine safe dosage levels and identify possible side effects.

It is also important to note that MEDI4736 has been studied in other cancer treatments, providing insight into its safety. However, using it with AZD5069 or AZD9150 is new, and ongoing studies are essential to learn how well patients handle these combinations. Participants should discuss any concerns with their healthcare provider before joining the trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the treatments MEDI4736, AZD9150, and AZD5069 for head and neck cancer because they offer innovative approaches compared to traditional therapies like surgery, radiation, and chemotherapy. Unlike standard treatments that often target the cancer cells directly, MEDI4736 is an immune checkpoint inhibitor that helps the immune system recognize and attack cancer cells more effectively. AZD9150 is a new type of antisense oligonucleotide designed to interfere with cancer cell growth at the genetic level, which is different from typical chemotherapy that targets rapidly dividing cells indiscriminately. AZD5069 is a CXCR2 antagonist that aims to disrupt cancer-supporting inflammation in the tumor environment, a novel strategy compared to existing treatments that focus primarily on the tumor itself. These unique mechanisms offer hope for improved outcomes and potentially fewer side effects.

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

This trial will evaluate the effectiveness of combining the drug MEDI4736 with either AZD5069 or AZD9150 for treating head and neck cancer. Research has shown that using MEDI4736 with AZD5069 can help the immune system better target cancer cells. Meanwhile, AZD9150 blocks a protein that aids cancer growth, potentially doubling response rates compared to MEDI4736 alone. This trial carefully studies both drug combinations for their potential to slow the disease and improve survival rates. ^{1 3 4 5 6}

Who Is on the Research Team?

David Hong, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

Adults with advanced solid tumors or relapsed metastatic squamous cell carcinoma of the head and neck, who have tried ≤3 previous cancer treatments (or none for certain arms), can join. They must be in good physical condition (ECOG PS 0 or 1) with proper organ function and measurable disease. Women of childbearing age and men with partners of childbearing potential must use effective birth control.

Inclusion Criteria

I am fully active or restricted in physically strenuous activity but can do light work.

I have had 1 to 3 rounds of chemotherapy to reduce my tumor size.

I have had 3 or fewer previous cancer treatments.

Exclusion Criteria

I have spinal cord compression but haven't needed steroids for it in the last 4 weeks.

Abnormalities in rhythm, conduction or morphology of resting 12-lead ECG

I have another cancer type besides SCCHN or was treated for another invasive cancer in the last 3 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose-escalation (Part A)

Patients with advanced solid malignancies receive escalating doses of AZD9150 or AZD5069 in combination with MEDI4736 to determine maximum tolerated doses (MTDs).

35 days

Multiple visits for dose escalation and monitoring

Dose-expansion (Part B)

Patients with recurrent/metastatic squamous cell carcinoma of the head and neck receive treatment based on the established MTDs to evaluate efficacy and safety.

Up to 12 months

Visits at every even-numbered cycle for assessment

Follow-up

Participants are monitored for safety and effectiveness after treatment until disease progression.

Up to 12 months

Follow-up visits until disease progression

What Are the Treatments Tested in This Trial?

Interventions

• AZD5069
• AZD9150
• MEDI4736

Trial Overview The trial is testing MEDI4736 combined with either AZD9150 or AZD5069, plus tremelimumab in some cases, to treat advanced cancers. It's a two-part study: Part A finds safe doses; Part B expands on those doses to further assess safety and effectiveness.

How Is the Trial Designed?

Group I: Part B8: AZD9150 (every other week)+MEDI4736: naive 1L Experimental Treatment 2 Interventions

Patients in Arm B8 will be evaluated for efficacy until disease progression and then followed up for safety and survival

Group II: Part B7: AZD9150+MEDI4736: naiive 1L Experimental Treatment 2 Interventions

Patients in Arm B7 will be evaluated for efficacy until disease progression and then followed up for safety and survival

Group III: Part B6:AZD5069 in naiive patients Experimental Treatment 1 Intervention

Patients in arm B6 will be evaluated for efficacy until disease progression and then allowed to receive additional MEDI4736 and followed for safety and survival

Group IV: Part B5: AZD9150 in naiive patients Experimental Treatment 1 Intervention

Patients in arm B5 will be evaluated for efficacy until disease progression and then allowed to receive additional MEDI4736 and followed for safety and survival

Group V: Part B4:AZD5069+MEDI4736:naiive patients Experimental Treatment 2 Interventions

Patients in arm B4 will be evaluated for efficacy until disease progression and then followed-up for safety and survival.

Group VI: Part B3: AZD9150+MED4736:naiive 2L Experimental Treatment 2 Interventions

Patients in arm B3 will be evaluated for efficacy until disease progression and then followed-up for safety and survival.

Group VII: Part B2:AZD5069+MEDI4736:PDL1 pretreated Experimental Treatment 2 Interventions

Patients in arm B2 will be evaluated for efficacy until disease progression and then followed-up for safety and survival.

Group VIII: Part B1:AZD9150+MEDI4736:PDL1 pretreated Experimental Treatment 2 Interventions

Patients in arm B1 will be evaluated for efficacy until disease progression and then followed-up for safety and survival.

Group IX: Part A7: AZD5069/MEDI4736 Experimental Treatment 2 Interventions

Patients allocated in cohort of arm A7 (AZD5069/MEDI4736) will be evaluated for safety, PK and PD.

Group X: Part A6: AZD9150/MEDI4736 Experimental Treatment 2 Interventions

Patients allocated in cohort of arm A6 (AZD9150/MEDI4736) will be evaluated for safety, PK and PD.

Group XI: Part A5: AZD5069/Treme/MEDI4736 Experimental Treatment 3 Interventions

Patients allocated in cohort of arm A5 (AZD5069/treme/MEDI4736) will be evaluated for DLT and MTD.

Group XII: Part A4: AZD9150/Treme/MEDI4736 Experimental Treatment 3 Interventions

Patients allocated in cohort of arm A4 (AZD9150/treme/MEDI4736) will be evaluated for DLT and MTD

Group XIII: Part A3: AZD5069/MEDI4736 Experimental Treatment 2 Interventions

Patients allocated in cohort of arm A3 (AZD5069/MEDI4736) will be evaluated for DLT and viability as alternate dosing option for Phase 2 studies

Group XIV: Part A2: AZD5069 / MEDI4736 Experimental Treatment 2 Interventions

Patients allocated in cohort of arm A2 (AZD5069/MEDI4736 will be evaluated for DLT until an MTD is achieved.

Group XV: Part A1: AZD9150 / MEDI4736 Experimental Treatment 2 Interventions

Patients allocated in cohort of arm A1 (AZD9150/MEDI4736 will be evaluated for DLT until an MTD is achieved.

Who Is Running the Clinical Trial?

AstraZeneca

Lead Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

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

Published Research Related to This Trial

The maximum tolerated dose (MTD) of paclitaxel given as a 96-hour continuous infusion during accelerated radiotherapy for advanced squamous cell carcinoma of the head and neck was determined to be 100 mg/m², with most patients completing the treatment without severe complications.

While some patients experienced significant side effects like Grade 4 mucositis and febrile neutropenia, all toxicities were reversible, and the treatment showed promising efficacy with complete responses in 8 out of 13 patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I trial of 96-hour paclitaxel infusion plus accelerated radiotherapy of unrespectable head and neck cancer. Machtay, M., Aviles, V., Kligerman, MM., et al.[2019]

The maximally tolerated dose (MTD) of afatinib when combined with carboplatin and paclitaxel for treating head and neck squamous cell carcinoma is determined to be 20 mg daily, as higher doses led to severe toxicities.

In a trial with nine patients, five showed a partial response and two had stable disease after induction chemotherapy, indicating some efficacy of the treatment combination, but caution is advised due to significant adverse effects at higher doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I study afatinib/carboplatin/paclitaxel induction chemotherapy followed by standard chemoradiation in HPV-negative or high-risk HPV-positive locally advanced stage III/IVa/IVb head and neck squamous cell carcinoma. Chung, CH., Rudek, MA., Kang, H., et al.[2018]

The JAVELIN Head and Neck 100 study is a Phase III clinical trial investigating the effectiveness of avelumab, a PD-L1 inhibitor, combined with standard chemoradiotherapy (CRT) for high-risk, locoregionally advanced squamous cell carcinomas of the head and neck.

This study addresses a critical gap in research, as there are currently no prospective studies evaluating immune checkpoint inhibitors in the definitive treatment of nonmetastatic HNSCC, which is important for improving outcomes in patients with poor prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

JAVELIN Head and Neck 100: a Phase III trial of avelumab and chemoradiation for locally advanced head and neck cancer. Yu, Y., Lee, NY.[2020]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9046875/

Therapeutic approaches for the treatment of head and neck ... Despite advances in numerous therapy modalities, survival rates for HNSCC have not improved considerably; a vast number of clinical outcomes have demonstrated ...

2. clinicaltrialsarena.com clinicaltrialsarena.com/marketdata/durvalumabs-recent-failure-head-and-neck-cancer/

Durvalumab's recent failure to demonstrate improved ... Durvalumab's recent failure to demonstrate improved overall survival highlights challenges in clinical development for head and neck cancer. On 5th February ...

3. annalsofoncology.org annalsofoncology.org/article/S0923-7534(20)38403-9/fulltext

Phase 1b/2 Study (SCORES) assessing safety, tolerability ... Phase 1b/2 Study (SCORES) assessing safety, tolerability, and preliminary anti-tumor activity of durvalumab plus AZD9150 or AZD5069 in patients with advanced ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT02499328

NCT02499328 | Study to Assess MEDI4736 With Either ... Study to Assess MEDI4736 With Either AZD9150 or AZD5069 in Advanced Solid Tumors & Relapsed Metastatic Squamous Cell Carcinoma of Head & Neck. ClinicalTrials ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11729135/

Selective anti-CXCR2 receptor blockade by AZD5069 ... The data show that the inhibitory actions of AZD5069 affect cell migration, albeit slightly differently under the concentrations tested in those ...

6. researchgate.net researchgate.net/publication/313340743_A_phase_1b_study_SCORES_assessing_safety_tolerability_pharmacokinetics_and_preliminary_anti-tumor_activity_of_durvalumab_combined_with_AZD9150_or_AZD5069_in_patients_with_advanced_solid_malignancies_a

A phase 1b study (SCORES) assessing safety, tolerability ... AZD5069, a CXCR2 inhibitor, is being evaluated in combination with durvalumab for solid cancers including bladder cancer in an early phase study ...