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

NCT02499328 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: D5660C000042015-002525-19
• Study Type: interventional
• Target: 340
• Locations: 6 countries
• Sites: 44

Brief Summary

This multicentre, open-label, Phase 1b/2 study is designed as a 2 part study consisting of a dose-escalation, safety run-in Part A and a dose-expansion Part B

Conditions

Advanced Solid Tumors & Metastatic Squamous Cell Carcinoma of the Head and Neck

Keywords

Carcinoma of the Head and Neck

Outcome Measures

Primary Outcomes (4)

• Part A: Danvatirsen With Durvalumab MTDs (Maximum Tolerated Dose) or Recommended Doses for Dose-expansion

  After completion of DLT period (35 days) for the maximum dose cohort. A CRM-based approach was used to identify the set of dose combinations where the incidence of DLT was ≤ 33%. The dose with expected DLT incidence closest and below 0.33 at this point was the "model estimated" MTD. During trial execution, the Safety Review Committee (SRC) determined the MTD.

  35 days

• Part A: AZD5069 With Durvalumab MTDs (Maximum Tolerated Dose) or Recommended Doses for Dose-expansion

  After completion of DLT period (35 days) for the maximum dose cohort. A CRM-based approach was used to identify the set of dose combinations where the incidence of DLT was ≤ 33%. The dose with expected DLT incidence closest and below 0.33 at this point was the "model estimated" MTD. During trial execution, the Safety Review Committee (SRC) determined the MTD.

  35 days

• Part A: Safety and Tolerability in Terms of Adverse Events

  Number of subjects with adverse events as a measure of safety and tolerability including changes in vital signs, electrocardiograms (ECGs), safety and laboratory parameters

  At every treatment and follow up visit until disease progression, an average of 1 year.

• Part B: ORR (Objective Response Rate) in Patients With IL/2L RM-SCCHN.

  proportion of patients who have an objective response at a given visit. ORR will be summarised by treatment group. Objective rate is defined as a CR or PR according to RECIST 1.1.

  Assessed at every even-numbered cycles with RECIST until disease progression, up to 12 months.

Secondary Outcomes (23)

• Part A and B: AZD9150 AUC0-6h at Lead in Day-7

  Lead in day -7, AUC from time 0 to 6h (post dose).

• Part A and B: AZD9150 Cmax at Lead in Day -7

  Lead in day -7

• Part A and B: AZD9150 AUC0-6h at Cycle 2 Day 1

  Cycle 2 day 1, AUC from time 0 to 6 h post dose

• Part A and B: AZD9150 Cmax at Cycle 2 Day 1

  Cycle 2 day 1

• Part A and B: AZD5069 AUC0-12h at Lead in Day -7

  Lead in day -7, AUC from time 0 to 12h post dose

Study Arms (15)

Part A1: AZD9150 / MEDI4736

EXPERIMENTAL

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

Drug: AZD9150; Drug: MEDI4736

Part A2: AZD5069 / MEDI4736

EXPERIMENTAL

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

Drug: MEDI4736; Drug: AZD5069

Part B1:AZD9150+MEDI4736:PDL1 pretreated

EXPERIMENTAL

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

Drug: AZD9150; Drug: MEDI4736

Part B2:AZD5069+MEDI4736:PDL1 pretreated

EXPERIMENTAL

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

Drug: MEDI4736; Drug: AZD5069

Part B3: AZD9150+MED4736:naiive 2L

EXPERIMENTAL

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

Drug: AZD9150; Drug: MEDI4736

Part B4:AZD5069+MEDI4736:naiive patients

EXPERIMENTAL

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

Drug: MEDI4736; Drug: AZD5069

Part B5: AZD9150 in naiive patients

EXPERIMENTAL

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

Drug: AZD9150

Part B6:AZD5069 in naiive patients

EXPERIMENTAL

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

Drug: AZD5069

Part A3: AZD5069/MEDI4736

EXPERIMENTAL

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

Drug: MEDI4736; Drug: AZD5069

Part A4: AZD9150/Treme/MEDI4736

EXPERIMENTAL

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

Drug: AZD9150; Drug: MEDI4736; Drug: tremelimumab (treme)

Part A5: AZD5069/Treme/MEDI4736

EXPERIMENTAL

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

Drug: MEDI4736; Drug: AZD5069; Drug: tremelimumab (treme)

Part A6: AZD9150/MEDI4736

EXPERIMENTAL

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

Drug: AZD9150; Drug: MEDI4736

Part A7: AZD5069/MEDI4736

EXPERIMENTAL

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

Drug: MEDI4736; Drug: AZD5069

Part B7: AZD9150+MEDI4736: naiive 1L

EXPERIMENTAL

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

Drug: AZD9150; Drug: MEDI4736

Part B8: AZD9150 (every other week)+MEDI4736: naive 1L

EXPERIMENTAL

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

Drug: AZD9150; Drug: MEDI4736

Interventions

MEDI4736 DRUG

MEDI4736

Part A1: AZD9150 / MEDI4736; Part A2: AZD5069 / MEDI4736; Part A3: AZD5069/MEDI4736; Part A4: AZD9150/Treme/MEDI4736; Part A5: AZD5069/Treme/MEDI4736; Part A6: AZD9150/MEDI4736; Part A7: AZD5069/MEDI4736; Part B1:AZD9150+MEDI4736:PDL1 pretreated; Part B2:AZD5069+MEDI4736:PDL1 pretreated; Part B3: AZD9150+MED4736:naiive 2L; Part B4:AZD5069+MEDI4736:naiive patients; Part B7: AZD9150+MEDI4736: naiive 1L; Part B8: AZD9150 (every other week)+MEDI4736: naive 1L

AZD5069 DRUG

AZD5069

Part A2: AZD5069 / MEDI4736; Part A3: AZD5069/MEDI4736; Part A5: AZD5069/Treme/MEDI4736; Part A7: AZD5069/MEDI4736; Part B2:AZD5069+MEDI4736:PDL1 pretreated; Part B4:AZD5069+MEDI4736:naiive patients; Part B6:AZD5069 in naiive patients

AZD9150 DRUG

AZD9150

Part A1: AZD9150 / MEDI4736; Part A4: AZD9150/Treme/MEDI4736; Part A6: AZD9150/MEDI4736; Part B1:AZD9150+MEDI4736:PDL1 pretreated; Part B3: AZD9150+MED4736:naiive 2L; Part B5: AZD9150 in naiive patients; Part B7: AZD9150+MEDI4736: naiive 1L; Part B8: AZD9150 (every other week)+MEDI4736: naive 1L

tremelimumab (treme) DRUG

tremelimumab

Part A4: AZD9150/Treme/MEDI4736; Part A5: AZD5069/Treme/MEDI4736

Eligibility Criteria

• Age: 18 Years - 130 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female patients must be at least 18 years of age.
• Has an Eastern Cooperative Oncology Group (ECOG) PS score of 0 or 1.
• Has measurable disease, defined as at least 1 lesion that can be accurately measured in at least 1 dimension (longest diameter to be recorded) with a minimum size of 10 mm by computerised tomography (CT) scan, except lymph nodes which must have minimum short axis size of 15 mm (CT scan slice thickness no greater than 5 mm in both cases). Indicator lesions must not have been previously treated with surgery, radiation therapy, or radiofrequency ablation unless there is documented progression after therapy.
• Has undergone ≤3 previous regimens (depending on treatment arm) of cytoreductive therapies including, but not limited to, platinum-based compounds, taxanes, or 5-fluorouracil. for B7 \& B8, no prior systemic treatments should have been received for RM SCCHN
• Adequate organ and marrow function
• Female subjects of childbearing potential and male subjects with partners of childbearing potential should ensure use of a highly effective method of birth control as defined in study protocol
• Arms B1-B6: Has undergone 1-3 previous regimens of cytoreductive chemo-therapies Arm B7 \& B8: with no prior exposure to anti-PD-(L)1 therapies and have received no prior systemic treatment for RM SCCHN

You may not qualify if:

• \- Spinal cord compression unless asymptomatic and not requiring steroids for at least 4 weeks before the start of study treatment. - Presently has a second malignancy other than SCCHN, or history of treatment for invasive cancer other than SCCHN in the past 3 years. Exceptions are: Previously treated in-situ carcinoma (ie, noninvasive) Cervical carcinoma stage 1B or less Noninvasive basal cell and squamous cell skin carcinoma Radically treated prostate cancer (prostatectomy or radiotherapy) with normal prostate-specific antigen, and not requiring ongoing antiandrogen hormonal therapy
• Patients must have completed any previous cancer-related treatments before enrolment. Any concurrent chemotherapy \[Chemotherapy washout within 21 days or 5 half-lives (whichever is shorter) from enrolment\], radiotherapy, immunotherapy, or biologic, or hormonal therapy for cancer excludes the patient (concurrent use of hormones for noncancer-related conditions \[eg, insulin for diabetes and hormone replacement therapy\] is acceptable),
• Experiencing CTCAE grade \>1 events, experienced immune-related grade ≥3AEs with prior immunotherapy
• Has active or prior autoimmune disease within the past 2 years
• Has active or prior inflammatory bowel disease or primary immunodeficiency
• Undergone an organ transplant that requires use of immunosuppressive treatment
• Abnormalities in rhythm, conduction or morphology of resting 12-lead ECG
• uncontrolled comorbid conditions
• Received a live attenuated vaccine within 30 days of first study dose, unable to take oral medications

Sponsors & Collaborators

• MedImmune LLC: collaborator
• AstraZeneca: lead

Study Sites (44)

Research Site

Birmingham, Alabama, 35294, United States

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Duarte, California, 91010, United States

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La Jolla, California, 92093, United States

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Los Angeles, California, 90024, United States

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Los Angeles, California, 90089, United States

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Orange, California, 92868-3298, United States

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San Francisco, California, 94158, United States

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Denver, Colorado, 80218, United States

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Plantation, Florida, 33324, United States

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Sarasota, Florida, 34232, United States

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Lafayette, Indiana, 47905, United States

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Boston, Massachusetts, 02111, United States

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Detroit, Michigan, 48201, United States

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Billings, Montana, 59101, United States

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Morristown, New Jersey, 07960, United States

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Cincinnati, Ohio, 45267-2827, United States

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Houston, Texas, 77030, United States

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Fairfax, Virginia, 22031, United States

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Seattle, Washington, 98109, United States

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Antwerp, 2020, Belgium

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Brussels, 1000, Belgium

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Brussels, 1200, Belgium

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Edegem, 2650, Belgium

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Namur, 5000, Belgium

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Berlin, 12200, Germany

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Cologne, 50670, Germany

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Dresden, 1307, Germany

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Frankfurt, 60488, Germany

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Hamburg, 20246, Germany

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Hanover, 30625, Germany

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Jena, 07743, Germany

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München, 81675, Germany

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Milan, 20133, Italy

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Barcelona, 08035, Spain

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Hospitalet deLlobregat, 08907, Spain

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Madrid, 28040, Spain

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Madrid, 28041, Spain

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Toledo, 45004, Spain

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Birmingham, B15 2TH, United Kingdom

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London, SE1 9RT, United Kingdom

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London, SW3 6JB, United Kingdom

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Manchester, M20 4BX, United Kingdom

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Surrey, SM2 5PT, United Kingdom

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Taunton, TA1 5DA, United Kingdom

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Related Links

• Related Info
• Related Info
• Redacted CSR synopsis

MeSH Terms

Interventions

danvatirsen; durvalumab; N-(2-(2,3-difluoro-6-benzylthio)-6-(3,4-dihydroxybutan-2-yloxy)pyrimidin-4-yl)azetidine-1-sulfonamide; tremelimumab

Results Point of Contact

• Title: Global Clinical Lead
• Organization: Astrazeneca

information.center@astrazeneca.com

1-877-240-9479

Study Officials

• Dr David Hong, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 18, 2015
• First Posted: July 16, 2015
• Study Start: August 6, 2015
• Primary Completion: February 28, 2020
• Study Completion: October 8, 2025
• Last Updated: February 11, 2026
• Results First Posted: November 23, 2021

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Locations

DE (8); IT (1); GB (6); BE (5); ES (5); US (19)