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

Lilly

Status and phase: Completed; Phase 1

Conditions: Gastric Cancer; Hepatocellular Carcinoma; Gastroesophageal Junction Adenocarcinoma; Non-Small Cell Lung Cancer

Treatments: Drug: MEDI4736; Drug: Ramucirumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT02572687

I4T-MC-JVDJ (Other Identifier)

16116

2015-003013-14 (EudraCT Number)

Details and patient eligibility

About

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).

Enrollment: 85 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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85 participants in 3 patient groups

Ramucirumab + MEDI4736 (NSCLC)

Experimental group

Description:

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.

Treatment:

Drug: MEDI4736

Drug: Ramucirumab

Ramucirumab + MEDI4736 (Gastric/GEJ)

Experimental group

Description:

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.

Treatment:

Drug: MEDI4736

Drug: Ramucirumab

Ramucirumab + MEDI4736 (HCC)

Experimental group

Description:

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.

Treatment:

Drug: MEDI4736

Drug: Ramucirumab