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

NCT02734160 | Completed Phase 1

• 3 other identifiers: 15784H9H-MC-JBEG2015-005295-26
• Study Type: interventional
• Target: 37
• Locations: 5 countries
• Sites: 11

Brief Summary

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.

Conditions

Metastatic Pancreatic Cancer

Keywords

immunotherapy; check point inhibitors; transforming growth factor (TGF)-beta R1 kinase inhibitor

Outcome Measures

Primary Outcomes (1)

• Number of Participants with Galunisertib in Combination with Durvalumab Dose-Limiting Toxicities (DLTs)

  Cycle 1 (28 Days)

Secondary Outcomes (10)

• 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)

Study Arms (1)

Galunisertib + Durvalumab

EXPERIMENTAL

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

Drug: Galunisertib; Drug: Durvalumab

Interventions

Galunisertib DRUG

Administered orally

Also known as: LY2157299

Galunisertib + Durvalumab

Durvalumab DRUG

Administered IV

Also known as: MEDI4736

Galunisertib + Durvalumab

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Eli Lilly and Company: lead
• AstraZeneca: collaborator

Study Sites (11)

Honor Health Research Institute

Scottsdale, Arizona, 85258, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Sarah Cannon Research Institute SCRI

Nashville, Tennessee, 37203, United States

Location

Tennessee Oncology PLLC

Nashville, Tennessee, 37203, United States

Location

Gustave Roussy

Villejuif, 94805, France

Location

Ospedale Policlinico Giambattista Rossi, Borgo Roma

Verona, 37134, Italy

Location

Samsung Medical Center

Seoul, Korea, 06351, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Madrid Norte Sanchinarro

Madrid, 28050, Spain

Location

Related Publications (1)

• 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.

  PMID: 33688022 DERIVED

Related Links

• Click here for more information about this study: A Study of Galunisertib (LY2157299) and Durvalumab (MEDI4736) in Participants With Metastatic Pancreatic Cancer

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

LY-2157299; durvalumab

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Study Officials

• 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

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: April 6, 2016
• First Posted: April 12, 2016
• Study Start: June 15, 2016
• Primary Completion: August 2, 2018
• Study Completion: April 17, 2019
• Last Updated: August 5, 2019

Record last verified: 2019-08-01

Locations

ES (3); IT (1); US (4); FR (1); KR (2)