A Phase I/II Study of MEDI4736 in Combination with Olaparib in Patients with Advanced Solid Tumors

Phase 1

Conditions: Initial stage cohort:SCLCgermline BRCA mutated (gBRCAm) metastatic human epidermal growthfactor receptor 2 (HER2) negative breast cancer (BC)gBRCAm platinum sensitive relapsed ovarian cancer (OvC)gastric cancerSecond stage cohort:BRCAm platinum sensitive relapsed OvCnon BRCAm platinum sensitive relapsed OvCThird stage cohort:HER2-negative, BRCAm BCHER2 negative, non BRCAm, Homologous Recombination Repair genemutated (HRRm) BCnon BRCAm, non HRRm triple negative BC
MedDRA version: 20.0Level: LLTClassification code 10033130Term: Ovarian cancer NOSSystem Organ Class: 100000004864
MedDRA version: 21.1Level: LLTClassification code 10071114Term: Metastatic gastric adenocarcinomaSystem Organ Class: 100000004864
MedDRA version: 20.0Level: LLTClassification code 10027475Term: Metastatic breast cancerSystem Organ Class: 100000004864
MedDRA version: 21.1Level: LLTClassification code 10041071Term: Small cell lung cancer stage unspecifiedSystem Organ Class: 100000004864
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2015-004005-16-GB

Lead Sponsor: Astra Zeneca AB

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 886

Inclusion Criteria

Inclusion criteria are presented separately for each cohort of Modules 1
to 10
Small cell lung cancer cohort:
Patients must have histologically or cytologically confirmed progressive
metastatic or recurrent solid tumor (as defined below for each tumor
type). To be enrolled in the SCLC cohort, only the tumor types and
settings described below are allowed (see in the Protocol)
At least 1 measurable lesion that can be accurately assessed at baseline
by computed tomography (CT) (or magnetic resonance imaging [MRI]
where CT is contraindicated) and is suitable for repeated assessment as
per RECIST 1.1. The baseline scan must be obtained
within 28 days prior to the first dose of olaparib. Biomarker-only disease
is not considered evaluable.
Breast cancer cohort:
Patients must have histologically or cytologically confirmed progressive
metastatic or recurrent solid tumor (as defined below for each tumor
type). To be enrolled in the gBRCAm breast cancer cohort, only the
tumor types and settings described below are allowed (see in the
Protocol).
At least 1 measurable lesion that can be accurately assessed at baseline
by computed tomography (CT) (or magnetic resonance imaging [MRI]
where CT is contraindicated) and is suitable for repeated assessment as
per RECIST 1.1. The baseline scan must be obtained
within 28 days prior to the first dose of olaparib. Biomarker-only disease
is not considered evaluable.
gBRCAm human epidermal growth factor receptor 2 (HER2)-negative
breast cancer patients with metastatic or locally advanced disease,
which is unresectable (or the patient is not a candidate for resection),
may be first, second or third line but all patients must meet the following
specific criteria:
Must have confirmation of a germline mutation in BRCA1 or BRCA2 that
is predicted to be deleterious or suspected deleterious (known or
predicted to be detrimental/lead to loss of function).
Must have previously received treatment with an anthracycline (eg,
doxorubicin, epirubicin) unless contraindicated and/or a taxane (eg,
paclitaxel, docetaxel) in either a neo-adjuvant/adjuvant or metastatic
setting.
gBRCAm ovarian cancer cohort:
Patients must have histologically or cytologically confirmed progressive
metastatic or recurrent solid tumor (as defined below for each tumor
type). To be enrolled in the gBRCAm ovarian cancer cohort, only the
tumor types and settings described below are allowed (see in
the Protocol).
At least 1 measurable lesion that can be accurately assessed at baseline
by computed tomography (CT) (or magnetic resonance imaging [MRI]
where CT is contraindicated) and is suitable for repeated assessment as
per RECIST 1.1. The baseline scan must be obtained
within 28 days prior to the first dose of olaparib. Biomarker-only
disease is not considered evaluable.
non-gBRCA ovarian cancer
High grade serous ovarian cancer (including patients with primary
peritoneal and/or fallopian tube cancer) with recurrent disease and:
Previously received 1 or 2 previous lines of chemotherapy, including =1
line of platinum-based therapy. NOTE: Adjuvant, neo-adjuvant, or
maintenance treatment administered as part of a chemotherapy regimen
would not be considered as separate line of therapy
Gastric cancer cohort:
Patients must have histologically or cytologically confirmed progressive
metastatic or recurrent solid tumor (as defined below for each tumor
type). To be enrolled in the gastric cancer cohort, only the tumor types
and settings described below are allowed

Exclusion Criteria

Exclusion criteria are presented separately for each cohort in Modules 1
to 9
Small cell lung cancer cohort:
Prior chemotherapy or other systemic anticancer therapy (eg, targeted
biotherapy or hormonal agents) within 4 weeks prior to start of olaparib
treatment; 6 weeks for nitrosoureas or mitomycin. Exceptions and
treatments of particular importance are noted below (see Protocol)
Radiation therapy within 4 weeks prior to start of olaparib treatment
(includes radiation targeting bone metastases) or radionuclide
treatment within 6 weeks of treatment start.
Patients with mixed small cell and non-small cell lung cancer histology.
Breast cancer cohort:
Prior chemotherapy or other systemic anticancer therapy (eg, targeted
biotherapy or hormonal agents) within 4 weeks prior to start of olaparib
treatment; 6 weeks for nitrosoureas or mitomycin. Exceptions and
treatments of particular importance are noted below (see the Protocol).
Radiation therapy within 4 weeks prior to start of olaparib treatment
(includes radiation targeting bone metastases) or radionuclide
treatment within 6 weeks of treatment start.
Patients with HER2-positive disease (3+ by immunohistochemistry [IHC]
or in situ hybridization amplified =2.0).
Patients cannot have received more than 2 prior lines of cytotoxic
chemotherapy for metastatic disease. Prior treatments with hormonal
therapy and non-hormonal targeted therapy are allowed and not counted
as a prior line of cytotoxic chemotherapy. For the purposes of this
protocol, the combination of an aromatase inhibitor and everolimus or
palbociclib, are not considered cytotoxic chemotherapy.
BRCA1 and/or BRCA2 variants that are considered to be non-detrimental
(eg, Variants of uncertain clinical significance or Variant of unknown
significance or Variant, favor polymorphism or benign
polymorphism etc).
gBRCAm ovarian cancer cohort:
Prior chemotherapy or other systemic anticancer therapy (eg, targeted
biotherapy or hormonal agents) within 4 weeks prior to start of olaparib
treatment; 6 weeks for nitrosoureas or mitomycin. Exceptions and
treatments of particular importance are noted below (see in the
Protocol).
Radiation therapy within 4 weeks prior to start of olaparib treatment
(includes radiation targeting bone metastases) or radionuclide
treatment within 6 weeks of treatment start.
Patients with germline BRCA1 and/or BRCA2 variants that are
considered to be non-detrimental (eg, Variants of uncertain clinical
significance or Variant of unknown significance or Variant, favor
polymorphism or benign polymorphism etc).
non-gBRCA ovarian
Patients with known germline BRCA1 and/or BRCA2 mutations, with the
exception of variants of uncertain clinical significance or Variant of
unknown significance or Variant, favor polymorphism or benign
polymorphism.
Gastric cancer cohort:
Prior chemotherapy or other systemic anticancer therapy (eg, targeted
biotherapy or hormonal agents) within 4 weeks prior to start of olaparib
treatment; 6 weeks for nitrosoureas or mitomycin. Exceptions and
treatments of particular importance are noted below (see in the
Protocol).
Radiation therapy within 4 weeks prior to start of olaparib treatment
(includes radiation targeting bone metastases) or radionuclide
treatment within 6 weeks of treatment start
For HER2-negative patients: More than 1 prior chemotherapy regimen
(except for adjuvant/neoadjuvant chemotherapy with more than 6
months wash-out period) for the treatment of gastric cancer i

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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