A Study Of Galunisertib (LY2157299) And Durvalumab (MEDI4736) In Participants With Metastatic Pancreatic Cancer

Study Overview

A Study of Galunisertib (LY2157299) and Durvalumab (MEDI4736) in Participants With Metastatic Pancreatic Cancer

The main purpose of this study is to evaluate the safety and efficacy of the study drug known as galunisertib administered in combination with the anti-programmed cell death-ligand 1 (PD-L1) antibody durvalumab in participants with refractory metastatic pancreatic cancer.

N/A

Metastatic Pancreatic Cancer

DRUG: Galunisertib
DRUG: Durvalumab

15784
H9H-MC-JBEG (OTHER Identifier) (OTHER: Eli Lilly and Company)
2015-005295-26 (EUDRACT_NUMBER Identifier) (EUDRACT_NUMBER: )

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2016-04-06	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2019-08-02
First Submitted that Met QC Criteria 2016-04-06	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2019-08-05
First Posted (ACTUAL) 2016-04-12	Results First Posted N/A	Last Verified 2019-08-01

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Galunisertib + Durvalumab (Dose Escalation and Cohort Expansion) Galunisertib administered orally in combination with durvalumab administered intravenously (IV).	DRUG: Galunisertib Administered orally DRUG: Durvalumab Administered IV

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: Galunisertib + Durvalumab

(Dose Escalation and Cohort Expansion) Galunisertib administered orally in combination with durvalumab administered intravenously (IV).

DRUG: Galunisertib

Administered orally

DRUG: Durvalumab

Administered IV

Primary Outcome Measures	Measure Description	Time Frame
Number of Participants with Galunisertib in Combination with Durvalumab Dose-Limiting Toxicities (DLTs)		Cycle 1 (28 Days)

Secondary Outcome Measures	Measure Description	Time Frame
Pharmacokinetics (PK): Maximum Concentration (Cmax) of Galunisertib		Predose Day 1 Cycle 1 through Predose Day 1 Cycle 7 (28 Day Cycles)
PK: Area Under the Curve (AUC) at Steady State of Galunisertib		Predose Day 1 Cycle 1 through Predose Day 1 Cycle 7 (28 Day Cycles)
PK: Minimum Concentration (Cmin) of Durvalumab		Predose Day 1 Cycle 1 through Predose Day 1 Cycle 7 (28 Day Cycles)
Number of Participants with Anti-Durvalumab Antibodies		Predose Day 1 Cycle 2 through Predose Day 1 Cycle 4 (28 Day Cycles)
Progression-free Survival (PFS)		Baseline to Objective Progressive Disease or Death (Estimated up to 18 Months)
Objective Response Rate (ORR): Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR)		Baseline to Objective Progressive Disease (Estimated up to 18 Months)
Duration of Response (DoR)		Date of CR or PR to Date of Objective Progressive Disease or Death Due to Any Cause (Estimated up to 18 Months)
Disease Control Rate (DCR): Percentage of Participants With a Best Overall Response of CR, PR, and Stable Disease (SD)		Baseline to Objective Progressive Disease or Start of New Anti-Cancer Therapy (Estimated up to 18 Months)
Time to Response		Baseline to Date of CR or PR (Estimated up to 4 Months)
Overall Survival (OS)		Baseline to Date of Death from Any Cause (Estimated up to 30 Months)

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

Must have histologic or cytologic confirmation of recurrent metastatic pancreatic adenocarcinoma based on standard diagnostic criteria. Recurrence must be documented by diagnostic biopsy.
Have measurable disease as defined by Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1.
Have had disease progression, been refractory or intolerant to no more than 2 prior systemic regimens for locally advanced or metastatic pancreatic cancer. Participants who have received prior neoadjuvant therapy and who now have metastatic disease must have received 1 of the following for their metastatic disease: FOLFIRINOX, nanoparticle albumin-bound paclitaxel/gemcitabine, TS-1 (tegafur gimeracil oteracil potassium), irinotecan liposome injection/5-fluorouracil (5FU)/Leucovorin or single-agent gemcitabine prior to enrolment in this study.
Dose Escalation: Able and willing to give valid written consent to undergo a new tumour biopsy (prior to study treatment) or to provide an available archival tumour sample if taken <3 years prior to enrolment if a new tumour biopsy is not feasible with an acceptable clinical risk.
Cohort Expansion: Able and willing to give valid written consent to undergo a new tumour biopsy (prior to study treatment). Able and willing to undergo a second tumour biopsy on treatment. Where possible, tumour lesions used for new biopsies should not be the same lesions used as RECIST target lesions, unless there are no other lesions suitable for biopsy. Archival samples may be required if there is inadequate tissue in the biopsy specimen.
Have adequate organ function.
Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale.
Use approved contraceptive methods.

Have moderate or severe cardiovascular disease:

Have the presence of cardiac disease, including a myocardial infarction within 6 months prior to study entry, unstable angina pectoris, New York Heart Association Class III/IV congestive heart failure, or uncontrolled hypertension.
Have documented major electrocardiogram (ECG) abnormalities (not responding to medical treatments; for example, atrial fibrillation, bundle branch blocks, or as approved by the sponsors).
Have major abnormalities documented by ECHO with Doppler (for example, moderate or severe heart valve function defect including moderate or severe valve stenosis or regurgitation, left ventricular ejection fraction <50%, evaluation based on the institutional lower limit of normal, septal aneurysm or other heart aneurysm, any aneurysm of the major vessels or any condition that results in increased risk of aneurysm (eg, Marfan syndrome, patent foramen ovale [PFO]).
Have predisposing conditions that are consistent with development of aneurysms of the ascending aorta or aortic stress (for example, family history of aneurysms, Marfan syndrome, PFO, bicuspid aortic valve, evidence of damage to the large vessels of the heart documented by computerized tomography [CT] scan with contrast or magnetic resonance imaging [MRI]).
Have evidence of interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity or active, noninfectious pneumonitis.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

AstraZeneca

Investigators

STUDY_DIRECTOR: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Melisi D, Oh DY, Hollebecque A, Calvo E, Varghese A, Borazanci E, Macarulla T, Merz V, Zecchetto C, Zhao Y, Gueorguieva I, Man M, Gandhi L, Estrem ST, Benhadji KA, Lanasa MC, Avsar E, Guba SC, Garcia-Carbonero R. Safety and activity of the TGFbeta receptor I kinase inhibitor galunisertib plus the anti-PD-L1 antibody durvalumab in metastatic pancreatic cancer. J Immunother Cancer. 2021 Mar;9(3):e002068. doi: 10.1136/jitc-2020-002068.

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