A Study of Ramucirumab (LY3009806) Plus MEDI4736 in Participants With Advanced Gastrointestinal or Thoracic Malignancies

• ClinicalTrials.gov Identifier: NCT02572687
• Recruitment Status: Completed
• First Posted: October 9, 2015
• Last Update Posted: January 20, 2021
• Sponsor: Eli Lilly and Company
• Collaborator: AstraZeneca
• Information provided by (Responsible Party): Eli Lilly and Company

Tracking Information

• First Submitted Date: October 7, 2015
• First Posted Date: October 9, 2015
• Last Update Posted Date: January 20, 2021
• Actual Study Start Date: February 19, 2016
• Actual Primary Completion Date: March 27, 2018 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: October 8, 2015): Number of Participants with Dose Limiting Toxicities (DLTs) [ Time Frame: Cycle 1 (up to 28 days) ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: October 8, 2015)

• Percentage of Participants with a Best Response of Complete Response (CR) or Partial Response (PR): Objective Response Rate (ORR) [ Time Frame: Baseline to Disease Progression (Approximately 22 Months) ]
• Proportion of Participants with a Best Overall Response of CR, PR, or Stable Disease (SD): Disease Control Rate (DCR) [ Time Frame: Baseline to Disease Progression (Approximately 22 Months) ]
• Duration of Response (DoR) [ Time Frame: Date of CR or PR to Date of Objective Disease Progression or Death Due to Any Cause (Approximately 22 Months) ]
• Time to First Response (TTR) [ Time Frame: Baseline to Date of CR or PR (Approximately 22 Months) ]
• Progression Free Survival (PFS) [ Time Frame: Baseline to Progressive Disease or Death from Any Cause (Approximately 22 Months) ]
• Overall Survival (OS) [ Time Frame: Baseline to Progressive Disease or Death from Any Cause (Approximately 32 Months) ]
• Pharmacokinetics (PK): Maximum Concentration (Cmax) of Ramucirumab and MEDI4736 [ Time Frame: Predose Cycle 1 Day 1 through Follow Up (Approximately 22 Months) ]
• PK: Minimum Concentration (Cmin) of Ramucirumab and MEDI4736 [ Time Frame: Predose Cycle 1 Day 1 through Follow up (Approximately 22 Months) ]
• Number of Participants with Treatment Emergent Anti Ramucirumab Antibodies [ Time Frame: Predose Cycle 1 Day 1 through Follow Up (Approximately 22 Months) ]
• Number of Participants with Treatment Emergent Anti MEDI4736 Antibodies [ Time Frame: Predose Cycle 1 Day 1 through Follow Up (Approximately 22 Months) ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of Ramucirumab (LY3009806) Plus MEDI4736 in Participants With Advanced Gastrointestinal or Thoracic Malignancies
• Official Title: An Open-Label, Multicenter, Phase 1 Study of Ramucirumab Plus MEDI4736 in Patients With Locally Advanced and Unresectable or Metastatic Gastrointestinal or Thoracic Malignancies
• Brief Summary: The main purpose of this study is to evaluate the safety of ramucirumab plus MEDI4736 in participants with locally advanced and unresectable or metastatic gastrointestinal or thoracic malignancies including gastric or gastroesophageal junction (GEJ) adenocarcinoma, non-small cell lung cancer (NSCLC), or hepatocellular carcinoma (HCC).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Gastric Cancer
• Gastroesophageal Junction Adenocarcinoma
• Non-Small Cell Lung Cancer
• Hepatocellular Carcinoma

Intervention

• Drug: Ramucirumab
  Administered IV
  Other Names:

  • LY3009806
  • IMC-11121B
  • Cyramza
• Drug: MEDI4736
  Administered IV

Study Arms

• Experimental: Ramucirumab + MEDI4736 (NSCLC)

  In phase 1a (DLT phase), ramucirumab plus MEDI4736 given intravenously (IV) every 3 weeks (q3w) of a 21 day treatment cycle. Participants may continue to receive study treatment until discontinuation criteria are met.

  In phase 1b (expansion phase), ramucirumab plus MEDI4736 given IV q3w. Participants may continue to receive study treatment until discontinuation criteria are met.

  Interventions:

  • Drug: Ramucirumab
  • Drug: MEDI4736
• Experimental: Ramucirumab + MEDI4736 (Gastric/GEJ)

  In phase 1a (DLT phase), ramucirumab plus MEDI4736 given IV every 2 weeks (q2w) of a 28 day treatment cycle. Participants may continue to receive study treatment until discontinuation criteria are met.

  In phase 1b (expansion phase), ramucirumab plus MEDI4736 given IV q2w. Participants may continue to receive study treatment until discontinuation criteria are met.

  Interventions:

  • Drug: Ramucirumab
  • Drug: MEDI4736
• Experimental: Ramucirumab + MEDI4736 (HCC)

  In phase 1a (DLT phase), ramucirumab plus MEDI4736 given IV q2w of a 28 day treatment cycle. Participants may continue to receive study treatment until discontinuation criteria are met.

  In phase 1b (expansion phase), ramucirumab plus MEDI4736 given IV q2w. Participants may continue to receive study treatment until discontinuation criteria are met.

  Interventions:

  • Drug: Ramucirumab
  • Drug: MEDI4736

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 18, 2021): 85
• Original Estimated Enrollment (submitted: October 8, 2015): 114
• Actual Study Completion Date: January 13, 2021
• Actual Primary Completion Date: March 27, 2018 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Measurable metastatic disease or locally advanced and unresectable disease

  • Has histopathologically confirmed gastric or GEJ adenocarcinoma with documented disease progression after 1-2 prior lines of systemic therapy
  • Has histopathologically confirmed nonsquamous or squamous NSCLC with documented disease progression after 1-3 prior lines of systemic therapy
  • Has histopathologically or cytologically confirmed HCC, Child-Pugh Class A, with documented disease progression during or after discontinuation of sorafenib therapy, or intolerance of sorafenib therapy, and an α-fetoprotein (AFP) ≥ 1.5x upper limit of normal
• Availability of tumor tissue for biomarker analysis
• Has an Eastern Cooperative Oncology Group Performance Status of 0 or 1
• Has adequate organ function

Exclusion Criteria:

• Has known brain metastases
• Has a history of prior cancers not included in this study that were either not treated with curative intent or have been active within the past 5 years
• History of allogeneic organ transplant
• Has active or prior documented autoimmune disease within the past 24 months
• Has human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS)-related illness, or a history of immunodeficiency
• Has active hepatitis B or hepatitis C infection, or co-infection with both hepatitis B and C virus
• For gastric/GEJ and NSCLC participants, has chronic hepatitis B or hepatitis C infection. (For HCC participants, those with chronic hepatitis B virus [HBV] infection with a negative HBV deoxyribonucleic acid [DNA] test and who are on antiviral therapy, and those with chronic hepatitis C virus [HCV] infection are eligible)
• Has a history of interstitial lung disease, idiopathic pulmonary fibrosis, pneumoconiosis, non-infections pneumonitis, radiation-induced or drug-induced pneumonitis
• Has received any previous systemic therapy targeting programmed death (PD) 1 or PD-ligand 1/2 signaling pathways, and other immune checkpoint inhibitors
• Have received previous systemic therapy with ramucirumab

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: France, Germany, Israel, Italy, Korea, Republic of, Spain, Taiwan, United States

Administrative Information

• NCT Number: NCT02572687
• Other Study ID Numbers: 16116; I4T-MC-JVDJ ( Other Identifier: Eli Lilly and Company ); 2015-003013-14 ( EudraCT Number )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Eli Lilly and Company
• Original Responsible Party: Same as current
• Current Study Sponsor: Eli Lilly and Company
• Original Study Sponsor: Same as current
• Collaborators: 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

• PRS Account: Eli Lilly and Company
• Verification Date: January 2021