A Study of Venetoclax and AMG 176 in Patients With Relapsed / Refractory Hematologic Malignancies

This dose-escalation study evaluating the safety, pharmacokinetics and preliminary efficacy of venetoclax in combination with AMG 176 in participants with relapsed or refractory acute myeloid leukemia (AML) and participants with Non-Hodgkin's lymphoma (NHL) / diffuse large B-cell lymphoma (DLBCL). This study will include a dose escalation phase to identify the maximum tolerated dose / recommended phase 2 dose (MTD / RPTD) of venetoclax plus AMG 176 as well as a dose expansion phase to confirm safety, explore efficacy, and confirm the suitability of the preliminary RPTD.

Inclusion Criteria

• Adequate kidney, liver and hematology values as described in the protocol.
• Diagnosis of relapsed or refractory (R/R) acute myeloid leukemia (AML) or R/R Non-Hodgkin's lymphoma (NHL)/diffuse large B-cell lymphoma (DLBCL) confirmed by the World Health Organization (WHO) criteria, as appropriate.
• Meets the following disease activity criteria:
• AML: must have received at least 1 prior therapy for AML and be ineligible for cytotoxic therapy and allogeneic stem cell transplant.
• NHL/DLBCL: measurable disease with a bidimensional lesion measuring at least 1.5 cm; received at least 1 prior therapy for NHL with no curative treatment option as determined by the investigator and be ineligible for a stem cell transplant.

Exclusion Criteria

• History of clinically significant medical condition that, in the opinion of the investigator, would adversely affect participation in this study.
• History of of any malignancy within the last 6 months except for those specified in this protocol and low-grade malignancies not requiring active treatment such as non-melanoma skin cancer, cervical intraepithelial neoplasia, or prostate cancer in situ.
• Prior allogeneic stem cell transplant or autologous stem cell transplant within 100 days of study drug administration and no signs or symptoms of acute or chronic graft-versus-host disease.
• Previous enrollment in a randomized trial including either venetoclax or AMG 176.
• Known active or chronic pancreatitis; severe chronic obstructive pulmonary disease with hypoxemia; central nervous system manifestations of malignancy.
• Active, uncontrolled infection.

Trial Phase Phase I

Trial Type Treatment

Lead Organization
Abbvie

• Primary ID M16-785
• Secondary IDs NCI-2019-00764, 2018-003314-41
• Clinicaltrials.gov ID NCT03797261