Clinical Trials /

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

NCT02499328

Description:

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

Related Conditions:
  • Breast Carcinoma
  • Hypopharyngeal Squamous Cell Carcinoma
  • Laryngeal Squamous Cell Carcinoma
  • Malignant Solid Tumor
  • Oral Cavity Squamous Cell Carcinoma
  • Oropharyngeal Squamous Cell Carcinoma
  • Prostate Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study to Assess MEDI4736 With Either AZD9150 or AZD5069 in Advanced Solid Tumors & Relapsed Metastatic Squamous Cell Carcinoma of Head & Neck
  • Official Title: A Phase 1b/2, Open-Label, Multicentre Study Assessing the Safety, Tolerability, Pharmacokinetics, and Preliminary Anti-tumor Activity of MEDI4736 in Combination With AZD9150 or AZD5069 in Patients With Advanced Solid Malignancies and Subsequently Comparing AZD9150 and AZD5069 Both as Monotherapy and in Combination With MEDI4736 as Second Line Treatment in Patients With Recurrent and/or Metastatic Squamous Cell Carcinoma of the Head and Neck

Clinical Trial IDs

  • ORG STUDY ID: D5660C00004
  • NCT ID: NCT02499328

Conditions

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

Interventions

DrugSynonymsArms
AZD9150Part A1: AZD9150 / MEDI4736
MEDI4736Part A1: AZD9150 / MEDI4736
AZD5069Part A2: AZD5069 / MEDI4736
tremelimumab (treme)Part A4: AZD9150/Treme/MEDI4736

Purpose

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

Detailed Description

The dose-escalation Part A of this study will involve patients with advanced solid malignancies refractory to standard therapy or for which no standard of care regimen currently exists. Approximately 30 evaluable patients per treatment arm (A1 or A2) will be enrolled. A3 will test viability of alternate dosing schedule for AZD5069, A4/A5 will evaluate AZD9150/AZd5069 in fixed dose combination with MEDI4736 and tremelimumab in solid tumors. there may also be safety run in cohorts enrolled (A6/A7) in specific solid tumor types (breast and prostate cancer).

Once the maximum tolerated doses (MTDs) for each of the 2 agents (AZD9150/AZD5069)in combination with MEDI4736 have been identified or the maximum doses of each of the 2 agents in combination with MEDI4736 have been reached, the dose expansion Part B of the study would commence. It will be conducted in patients with recurrent and/or metastatic (RM) squamous cell carcinoma of the head and neck (SCCHN). Between 68 and 124 eligible patients will be enrolled and will randomly assigned to 1 of the following 6 treatment arms:

- Treatment arm B1: AZD9150 in combination with MEDI4736 in patients with prior exposure to anti-PD-(L)1 antibodies

- Treatment arm B2: AZD5069 in combination with MEDI4736 in patients with prior exposure to anti-PD-(L)1 antibodies

- Treatment arm B3: AZD9150 in combination with MEDI4736 in patients with no prior exposure to anti-PD-(L)1 antibodies

- Treatment arm B4: AZD5069 in combination with MEDI4736 in patients with no prior exposure to anti-PD-(L)1 antibodies

- Treatment arm B5: AZD9150 alone in patients with no prior exposure to anti-PD-(L)1 antibodies

- Treatment arm B6: AZD5069 alone in patients with no prior exposure to anti-PD-(L)1 antibodies

Trial Arms

NameTypeDescriptionInterventions
Part A1: AZD9150 / MEDI4736ExperimentalPatients allocated in cohort of arm A1 (AZD9150/MEDI4736 will be evaluated for DLT until an MTD is achieved.
  • AZD9150
  • MEDI4736
    Part A2: AZD5069 / MEDI4736ExperimentalPatients allocated in cohort of arm A2 (AZD5069/MEDI4736 will be evaluated for DLT until an MTD is achieved.
      • MEDI4736
      • AZD5069
      Part B1:AZD9150+MEDI4736:PDL1 pretreatedExperimentalPatients in arm B1 will be evaluated for efficacy until disease progression and then followed-up for safety and survival.
      • AZD9150
      • MEDI4736
        Part B2:AZD5069+MEDI4736:PDL1 pretreatedExperimentalPatients in arm B2 will be evaluated for efficacy until disease progression and then followed-up for safety and survival.
          • MEDI4736
          • AZD5069
          Part B3: AZD9150+MED4736:naiive patientsExperimentalPatients in arm B3 will be evaluated for efficacy until disease progression and then followed-up for safety and survival.
          • AZD9150
          • MEDI4736
            Part B4:AZD5069+MEDI4736:naiive patientsExperimentalPatients in arm B4 will be evaluated for efficacy until disease progression and then followed-up for safety and survival.
              • MEDI4736
              • AZD5069
              Part B5: AZD9150 in naiive patientsExperimentalPatients in arm B5 will be evaluated for efficacy until disease progression and then allowed to receive additional MEDI4736 and followed for safety and survival
              • AZD9150
                Part B6:AZD5069 in naiive patientsExperimentalPatients in arm B6 will be evaluated for efficacy until disease progression and then allowed to receive additional MEDI4736 and followed for safety and survival
                    • AZD5069
                  Part A3: AZD5069/MEDI4736ExperimentalPatients allocated in cohort of arm A3 (AZD5069/MEDI4736) will be evaluated for DLT and viability as alternate dosing option for Phase 2 studies
                    • MEDI4736
                    • AZD5069
                    Part A4: AZD9150/Treme/MEDI4736ExperimentalPatients allocated in cohort of arm A4 (AZD9150/treme/MEDI4736) will be evaluated for DLT and MTD
                    • AZD9150
                    • MEDI4736
                      • tremelimumab (treme)
                    Part A5: AZD5069/Treme/MEDI4736ExperimentalPatients allocated in cohort of arm A5 (AZD5069/treme/MEDI4736) will be evaluated for DLT and MTD.
                      • MEDI4736
                      • AZD5069
                      • tremelimumab (treme)
                    Part A6: AZD9150/MEDI4736ExperimentalPatients allocated in cohort of arm A6 (AZD9150/MEDI4736) will be evaluated for safety, PK and PD.
                    • AZD9150
                    • MEDI4736
                      Part A7: AZD5069/MEDI4736ExperimentalPatients allocated in cohort of arm A7 (AZD5069/MEDI4736) will be evaluated for safety, PK and PD.
                        • MEDI4736
                        • AZD5069

                        Eligibility Criteria

                        Key Inclusion Criteria:

                        - 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 of cytoreductive therapies including, but not limited to, platinum-based compounds, taxanes, or 5-fluorouracil.

                        - 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

                        - Additional inclusion for part A: Has a histological confirmation of a solid malignancy (other than HCC) that is refractory to standard therapy or for which no standard of care regimen currently exists.

                        - Addition inclusion for Part A (A6 & A7) Has a histological confirmation of either metastatic breast (ER+ve for Arm A6, 50% ER +ve and 50% HER2+ve metastatic breast cancer patients for Arm A7) or castrate-resistant prostate cancer

                        - Additional inclusion for Part B:Has histologically and/or cytologically confirmed SCCHN that is RM and not amendable to curative therapy by surgery or radiation. Squamous cell carcinoma of the head and neck originating from the following sites is eligible: oral cavity, oropharynx, larynx, or hypopharynx. Has at least 1 SCCHN tumour lesion (TL) amenable to biopsy and must have failed, refused, or has been found to be ineligible for least 1 prior platinum-based chemotherapy for RM-SCCHN Additional inclusion criteria for Arms B1 & B2:must have had prior exposure to anti PDL-1 antibody

                        Key Exclusion Criteria:

                        - 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, 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 28 days of first study dose, unable to take oral medications

                        - History of allergic reactions to study compounds or excepients Additional exclusion criteria Part A: Patients with clinically active brain metastases and prior exposure to AZD9150, AZD5069, MEDI4736, or any other anti PD (L)1 antibody.

                        Additional exclusion criteria Part B: Patients with brain metastases (known or suspected) Additional exclusion criteria Part B: treatment arms B3, B4, B5, and B6: prior exposure to AZD9150, AZD5069, MEDI4736, or any other anti PD (L)1 antibody.

                        Maximum Eligible Age:130 Years
                        Minimum Eligible Age:18 Years
                        Eligible Gender:All
                        Healthy Volunteers:No

                        Primary Outcome Measures

                        Measure:Part A: MTDs (Maximum Tolerated Dose) or recommended doses for dose-expansion
                        Time Frame:35 days
                        Safety Issue:
                        Description:After completion of DLT period (35 days) for the maximum dose cohort. Expected to be achieved within 6 months of first subject dosed

                        Secondary Outcome Measures

                        Measure:Part A and B: Evaluation of pharmacokinetics, Pharmacodynamics, immunogenecity and translational biomarkers
                        Time Frame:during leadin period, and cycles 1 and 2, an average of 1 year
                        Safety Issue:
                        Description:
                        Measure:Part A: Antitumour activity in monotherapy and combination arms of study
                        Time Frame:assessed at every numbered cycle with RECIST until disease progression. Expected to be for a period up to 12 months
                        Safety Issue:
                        Description:complete response, partial response, stable disease or progressive disease based on RECIST
                        Measure:Part B: Safety and tolerability in terms of AEs
                        Time Frame:At every treatment visit and 28 days after last dose. In patients with MedI4736 for IM (Immunogenicity) 90 days after last dose.
                        Safety Issue:
                        Description:
                        Measure:Part B: Secondary measures change in efficacy
                        Time Frame:Assessed at every even-numbered cycles.assessed at every numbered cycle with RECIST until disease progression. Expected to be for a period up to 12 months
                        Safety Issue:
                        Description:Disease control rate; Duration of overall response; progression-free survival (PFS); overall survival (OS); and proportion of patients alive at 12 months)

                        Details

                        Phase:Phase 1/Phase 2
                        Primary Purpose:Interventional
                        Overall Status:Recruiting
                        Lead Sponsor:AstraZeneca

                        Trial Keywords

                        • Carcinoma of the Head and Neck

                        Last Updated

                        January 11, 2017