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

Primary Purpose

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

Status

Active

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

AZD9150

MEDI4736

AZD5069

tremelimumab (treme)

About this trial

This is an interventional treatment trial for Advanced Solid Tumors & Metastatic Squamous Cell Carcinoma of the Head and Neck focused on measuring Carcinoma of the Head and Neck

Eligibility Criteria

18 Years - 130 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 (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
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) Has a histological confirmation of 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
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

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 [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
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, B6, B7 and B8: prior exposure to AZD9150, AZD5069, MEDI4736, or any other anti PD (L)1 antibody.

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm 10

Arm 11

Arm 12

Arm 13

Arm 14

Arm 15

Arm Type

Experimental

Arm Label

Part A1: AZD9150 / MEDI4736

Part A2: 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 B5: AZD9150 in naiive patients

Part B6:AZD5069 in naiive patients

Part A3: AZD5069/MEDI4736

Part A4: AZD9150/Treme/MEDI4736

Part A5: AZD5069/Treme/MEDI4736

Part A6: AZD9150/MEDI4736

Part A7: AZD5069/MEDI4736

Part B7: AZD9150+MEDI4736: naiive 1L

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

Arm Description

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Outcomes

Primary Outcome Measures

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.

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

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

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.

Secondary Outcome Measures

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

If a subjects had at least one post dose PK sample they were part of PK analysis set. However, to calculate AUC, we need to have enough PK samples collected to enable AUC estimation. That is why we have a difference in actual AUC calculated number of subjects vs number of subjects participated.

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

If a subjects had at least one post dose PK sample they were part of PK analysis set. However, to estimate Cmax we need to have samples at end of infusion, which was not available for all the subjects in PK analysis set. That is why there is a difference between Cmax calculated number of subjects vs number of subjects participated.

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

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

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

Part A and B: AZD5069 Cmax at Lead in Day -7

If a subjects had at least one post dose PK sample they were part of PK analysis set. However, to estimate Cmax we need to have samples at Tmax, which was not available for all the subjects in PK analysis set. That is why there is a difference between Cmax calculated number of subjects vs number of subjects participated.

Part A and B: AZD5069 Cssmax at Cycle 2 Day 1

If a subjects had at least one post dose PK sample they were part of PK analysis set. However, to estimate Cmax we need to have samples at around Tmax, which was not available for all the subjects in PK analysis set. That is why there is a difference between Cmax calculated number of subjects vs number of subjects participated.

Part A and B: AZD5069 AUCss at Cycle 2 Day 1

Part A and B: Durvalumab Cmax After Single Dose at Cycle 1 Day 1

Part A and B: Durvalumab Ctrough After Multiple Doses at Cycle 4 Day 1

If a subjects had at least one post dose PK sample they were part of PK analysis set. However, to estimate Ctrough we need to have samples at predose, which was not available for all the subjects in PK analysis set. That is why there is a difference between Ctrough calculated number of subjects vs number of subjects participated.

Part A and B: Durvalumab Cmax After Multiple Doses at Cycle 8 Day 1

Part A and B: Treme Cmax After Single Dose

Part A and B: Treme Ctrough After Multiple Doses at Cycle 4 Day 1

Part A and B: Immunogenecity as Percent of ADA Positive Subjects

Subject was considered ADA positive if any post dose samples had ADA positive result. Result was not stratified based on post dose time points.

Part A: Antitumour Activity in Monotherapy and Combination Arms of Study

complete response, partial response, stable disease or progressive disease based on RECIST

Part B: 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

Part B: Secondary Measures Change in Efficacy - Disease Control Rate

Disease control rate is confirmed complete response (CR), confirmed partial response (PR) and stable disease (SD)

Part B: Secondary Measures Change in Efficacy - Duration of Overall Response

Duration of overall response is according to RECIST 1.1 criteria measured from the time measurement criteria are first met for CR or PR, whichever is first recorded, until the first date that recurrent or PD is objectively documented (taking as reference for PD the smallest measurements recorded on study). DOR is only applied to treatment groups where at least one response patient was recorded.

Part B: Secondary Measures Change in Efficacy - PFS

progression-free survival (PFS): defined as the time from randomisation to the first documentation of PD as determined by the Investigator or death from any cause, whichever occurs first. Only includes progression events that occur within 126 days of the last evaluable assessment

Part B: Secondary Measures Change in Efficacy - OS

overall survival (OS) - defined as the time from treatment allocation to death from any cause

Part B: Secondary Measures Change in Efficacy - OS at 12 Months

proportion of patients alive at 12 months: the percentage of patients surviving at 12 months after randomization to study drug

Part B: Evaluation of AZD9150 Pharmacodynamics: Change in STAT3 RNA Level From Baseline

Percent STAT3 RNA change in expression level in peripheral blood in patients who had baseline (Screening or Day -7) sample for comparison. Data were only available for B1, B3, B5, B7 and B8.

Part B: Evaluation of PDL1 Expression

Tumors with PDL1-positive tumor cells at the designated cutoff. Data were only available for B1, B2, B3, B4, B7 and B8.

Full Information

NCT ID

NCT02499328

First Posted

June 18, 2015

Last Updated

August 18, 2023

Sponsor

AstraZeneca

Collaborators

MedImmune LLC

1. Study Identification

Unique Protocol Identification Number

NCT02499328

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.

Study Type

Interventional

2. Study Status

Record Verification Date

August 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

August 6, 2015 (Actual)

Primary Completion Date

February 28, 2020 (Actual)

Study Completion Date

December 29, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

AstraZeneca

Collaborators

MedImmune LLC

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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

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 266 eligible patients will be enrolled and will randomly assigned to 1 of the following 6 treatment arms or non randomized arm B7: 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 (2L RM SCCHN) 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 Treatment arm B7: (non randomized): AZD9150 in combination with MEDI4736 in patients with no prior exposure to anti-PD-(L)1 antibodies (1L RM SCCHN) Treatment arm B8: (non randomized): AZD9150 (every two weeks) in combination with MEDI4736 in patients with no prior exposure to anti-PD-(L)1 antibodies (1L RM SCCHN)

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

Keywords

Carcinoma of the Head and Neck

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

340 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Part A1: AZD9150 / MEDI4736

Arm Type

Experimental

Arm Description

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

Arm Title

Part A2: AZD5069 / MEDI4736

Arm Type

Experimental

Arm Description

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

Arm Title

Part B1:AZD9150+MEDI4736:PDL1 pretreated

Arm Type

Experimental

Arm Description

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

Arm Title

Part B2:AZD5069+MEDI4736:PDL1 pretreated

Arm Type

Experimental

Arm Description

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

Arm Title

Part B3: AZD9150+MED4736:naiive 2L

Arm Type

Experimental

Arm Description

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

Arm Title

Part B4:AZD5069+MEDI4736:naiive patients

Arm Type

Experimental

Arm Description

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

Arm Title

Part B5: AZD9150 in naiive patients

Arm Type

Experimental

Arm Description

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

Arm Title

Part B6:AZD5069 in naiive patients

Arm Type

Experimental

Arm Description

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

Arm Title

Part A3: AZD5069/MEDI4736

Arm Type

Experimental

Arm Description

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

Arm Title

Part A4: AZD9150/Treme/MEDI4736

Arm Type

Experimental

Arm Description

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

Arm Title

Part A5: AZD5069/Treme/MEDI4736

Arm Type

Experimental

Arm Description

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

Arm Title

Part A6: AZD9150/MEDI4736

Arm Type

Experimental

Arm Description

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

Arm Title

Part A7: AZD5069/MEDI4736

Arm Type

Experimental

Arm Description

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

Arm Title

Part B7: AZD9150+MEDI4736: naiive 1L

Arm Type

Experimental

Arm Description

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

Arm Title

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

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

AZD9150

Intervention Description

AZD9150

Intervention Type

Drug

Intervention Name(s)

MEDI4736

Intervention Description

MEDI4736

Intervention Type

Drug

Intervention Name(s)

AZD5069

Intervention Description

AZD5069

Intervention Type

Drug

Intervention Name(s)

tremelimumab (treme)

Intervention Description

tremelimumab

Primary Outcome Measure Information:

Title

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

Description

Time Frame

35 days

Title

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

Description

Time Frame

35 days

Title

Part A: Safety and Tolerability in Terms of Adverse Events

Description

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

Time Frame

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

Title

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

Description

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.

Time Frame

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

Secondary Outcome Measure Information:

Title

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

Description

Time Frame

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

Title

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

Description

Time Frame

Lead in day -7

Title

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

Description

Time Frame

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

Title

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

Time Frame

Cycle 2 day 1

Title

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

Description

Time Frame

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

Title

Part A and B: AZD5069 Cmax at Lead in Day -7

Description

Time Frame

Lead in day -7

Title

Part A and B: AZD5069 Cssmax at Cycle 2 Day 1

Description

Time Frame

Cycle 2 day 1

Title

Part A and B: AZD5069 AUCss at Cycle 2 Day 1

Description

Time Frame

Cycle 2 day 1

Title

Part A and B: Durvalumab Cmax After Single Dose at Cycle 1 Day 1

Time Frame

Cycle 1 day 1

Title

Part A and B: Durvalumab Ctrough After Multiple Doses at Cycle 4 Day 1

Description

Time Frame

Cycle 4 day 1

Title

Part A and B: Durvalumab Cmax After Multiple Doses at Cycle 8 Day 1

Description

Time Frame

Cycle 8 day 1

Title

Part A and B: Treme Cmax After Single Dose

Description

Time Frame

Cycle 1 day 1

Title

Part A and B: Treme Ctrough After Multiple Doses at Cycle 4 Day 1

Description

Time Frame

Cycle 4 day 1

Title

Part A and B: Immunogenecity as Percent of ADA Positive Subjects

Description

Subject was considered ADA positive if any post dose samples had ADA positive result. Result was not stratified based on post dose time points.

Time Frame

Throughout the study, up to 3.3 years

Title

Part A: Antitumour Activity in Monotherapy and Combination Arms of Study

Description

complete response, partial response, stable disease or progressive disease based on RECIST

Time Frame

assessed at every even numbered cycle with RECIST until disease progression, an average of 1 year

Title

Part B: Safety and Tolerability in Terms of Adverse Events

Description

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

Time Frame

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

Title

Part B: Secondary Measures Change in Efficacy - Disease Control Rate

Description

Disease control rate is confirmed complete response (CR), confirmed partial response (PR) and stable disease (SD)

Time Frame

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

Title

Part B: Secondary Measures Change in Efficacy - Duration of Overall Response

Description

Time Frame

Assessed at every even-numbered cycles. Assessed at every even numbered cycle with RECIST until disease progression, up to 48 months

Title

Part B: Secondary Measures Change in Efficacy - PFS

Description

Time Frame

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

Title

Part B: Secondary Measures Change in Efficacy - OS

Description

overall survival (OS) - defined as the time from treatment allocation to death from any cause

Time Frame

Assessed at every even-numbered cycles. Assessed at every even numbered cycle with RECIST until disease progression, up to 15 months

Title

Part B: Secondary Measures Change in Efficacy - OS at 12 Months

Description

proportion of patients alive at 12 months: the percentage of patients surviving at 12 months after randomization to study drug

Time Frame

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

Title

Part B: Evaluation of AZD9150 Pharmacodynamics: Change in STAT3 RNA Level From Baseline

Description

Percent STAT3 RNA change in expression level in peripheral blood in patients who had baseline (Screening or Day -7) sample for comparison. Data were only available for B1, B3, B5, B7 and B8.

Time Frame

At Cycle 2 Day 1 vs. Baseline

Title

Part B: Evaluation of PDL1 Expression

Description

Tumors with PDL1-positive tumor cells at the designated cutoff. Data were only available for B1, B2, B3, B4, B7 and B8.

Time Frame

in baseline tumor samples

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

130 Years

Accepts Healthy Volunteers

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 (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 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) Has a histological confirmation of 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 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 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 [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 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, B6, B7 and B8: prior exposure to AZD9150, AZD5069, MEDI4736, or any other anti PD (L)1 antibody.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Dr David Hong, MD

Organizational Affiliation

M.D. Anderson Cancer Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

Research Site

City

Birmingham

State/Province

Alabama

ZIP/Postal Code

35294

Country

United States

Facility Name

Research Site

City

Duarte

State/Province

California

ZIP/Postal Code

91010

Country

United States

Facility Name

Research Site

City

La Jolla

State/Province

California

ZIP/Postal Code

92093

Country

United States

Facility Name

Research Site

City

Los Angeles

State/Province

California

ZIP/Postal Code

90024

Country

United States

Facility Name

Research Site

City

Los Angeles

State/Province

California

ZIP/Postal Code

90089

Country

United States

Facility Name

Research Site

City

Orange

State/Province

California

ZIP/Postal Code

92868-3298

Country

United States

Facility Name

Research Site

City

San Francisco

State/Province

California

ZIP/Postal Code

94158

Country

United States

Facility Name

Research Site

City

Denver

State/Province

Colorado

ZIP/Postal Code

80218

Country

United States

Facility Name

Research Site

City

Plantation

State/Province

Florida

ZIP/Postal Code

33324

Country

United States

Facility Name

Research Site

City

Sarasota

State/Province

Florida

ZIP/Postal Code

34232

Country

United States

Facility Name

Research Site

City

Lafayette

State/Province

Indiana

ZIP/Postal Code

47905

Country

United States

Facility Name

Research Site

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02111

Country

United States

Facility Name

Research Site

City

Detroit

State/Province

Michigan

ZIP/Postal Code

48201

Country

United States

Facility Name

Research Site

City

Billings

State/Province

Montana

ZIP/Postal Code

59101

Country

United States

Facility Name

Research Site

City

Morristown

State/Province

New Jersey

ZIP/Postal Code

07960

Country

United States

Facility Name

Research Site

City

Cincinnati

State/Province

Ohio

ZIP/Postal Code

45267-2827

Country

United States

Facility Name

Research Site

City

Houston

State/Province

Texas

ZIP/Postal Code

77030

Country

United States

Facility Name

Research Site

City

Fairfax

State/Province

Virginia

ZIP/Postal Code

22031

Country

United States

Facility Name

Research Site

City

Seattle

State/Province

Washington

ZIP/Postal Code

98109

Country

United States

Facility Name

Research Site

City

Antwerpen

ZIP/Postal Code

2020

Country

Belgium

Facility Name

Research Site

City

Brussels

ZIP/Postal Code

1000

Country

Belgium

Facility Name

Research Site

City

Bruxelles

ZIP/Postal Code

1200

Country

Belgium

Facility Name

Research Site

City

Edegem

ZIP/Postal Code

2650

Country

Belgium

Facility Name

Research Site

City

Namur

ZIP/Postal Code

5000

Country

Belgium

Facility Name

Research Site

City

Berlin

ZIP/Postal Code

12200

Country

Germany

Facility Name

Research Site

City

Dresden

ZIP/Postal Code

1307

Country

Germany

Facility Name

Research Site

City

Frankfurt

ZIP/Postal Code

60488

Country

Germany

Facility Name

Research Site

City

Hamburg

ZIP/Postal Code

20246

Country

Germany

Facility Name

Research Site

City

Hannover

ZIP/Postal Code

30625

Country

Germany

Facility Name

Research Site

City

Jena

ZIP/Postal Code

07743

Country

Germany

Facility Name

Research Site

City

Köln

ZIP/Postal Code

50670

Country

Germany

Facility Name

Research Site

City

München

ZIP/Postal Code

81675

Country

Germany

Facility Name

Research Site

City

Milano

ZIP/Postal Code

20133

Country

Italy

Facility Name

Research Site

City

Barcelona

ZIP/Postal Code

08035

Country

Spain

Facility Name

Research Site

City

Hospitalet deLlobregat

ZIP/Postal Code

08907

Country

Spain

Facility Name

Research Site

City

Madrid

ZIP/Postal Code

28040

Country

Spain

Facility Name

Research Site

City

Madrid

ZIP/Postal Code

28041

Country

Spain

Facility Name

Research Site

City

Toledo

ZIP/Postal Code

45004

Country

Spain

Facility Name

Research Site

City

Birmingham

ZIP/Postal Code

B15 2TH

Country

United Kingdom

Facility Name

Research Site

City

London

ZIP/Postal Code

SE1 9RT

Country

United Kingdom

Facility Name

Research Site

City

London

ZIP/Postal Code

SW3 6JB

Country

United Kingdom

Facility Name

Research Site

City

Manchester

ZIP/Postal Code

M20 4BX

Country

United Kingdom

Facility Name

Research Site

City

Taunton

ZIP/Postal Code

TA1 5DA

Country

United Kingdom

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

IPD Sharing 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.

IPD Sharing 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.

IPD Sharing URL

https://astrazenecagroup-dt.pharmacm.com/DT/Home

Links:

URL

https://filehosting-v2.pharmacm.com/api/Attachment/Download?tenantId=80217111&parentIdentifier=D5660C00004&attachmentIdentifier=6196e810-bbae-4179-a8b2-f9d0b2f5b623&fileName=d5660c00004-sap-V4.0_Redacted_PDFA.pdf&versionIdentifier=

Description

Related Info

URL

https://filehosting-v2.pharmacm.com/api/Attachment/Download?tenantId=80217111&parentIdentifier=D5660C00004&attachmentIdentifier=94d1da6c-8b9b-48d3-9ff9-106e83189cc4&fileName=d5660c00004-csp-v12-amendment-11_-_Redacted_03Feb2021.pdf&versionIdentifier=

Description

Related Info

Learn more about this trial

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

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

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

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm 10

Arm 11

Arm 12

Arm 13

Arm 14

Arm 15

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial