BGB-3111 & A317 (BGB-Combo)

BGB-3111 & A317 (BGB-Combo)

A Phase 1b, Open Label, Multiple Dose, Dose Escalation and Expansion Study to Assess Safety, Tolerability and Antitumor Activities of the Combination of BGB-3111 with BGB-A317 in Subjects with B-Cell Lymphoid Malignancies

Disease:

Lymphoma -> small lymphocytic lymphoma (SLL), mantle cell lymphoma (MCL), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), marginal zone lymphoma (MZL), hairy cell leukaemia (HCL), transformed indolent lymphoma to diffuse large B-cell lymphoma, central nervous system lymphoma

Summary:

Non-Hodgkin lymphomas are cancers of white blood cells that can be divided into indolent (slow growing) and aggressive (fast growing), though they share common pathways that can be targeted by anti-cancer drugs.

This trial is for patients who have non-Hodgkin lymphoma which has returned after treatment. Patients will receive BGB-3111 (zanubrutinib) and BGB-A317 (tisleblizumab). Zanubrutinib is taken by mouth, and works by targeting an important part of the cancer cell called Bruton’s tyrosine kinase (Btk), which causes the cells to die. Tisleblizumab is give through an intravenous drip and works by ‘revealing’ the cancer to the immune system to be killed.

The aim of the trial is to see whether the combination of medications is effective and safe in patients with non-Hodgkin lymphoma.

Eligibility:

Include, but not limited to, the following:

Inclusion Criteria:
1. Dose expansion (Cohorts 1-4): Subjects with either of the following relapsed or
refractory WHO-classified lymphoid malignancies who have received at least 1 prior
line of standard therapy:
a. Cohort 1: GCB DLBCL, with cell of origin defined by
either immunohistochemistry or gene expression profiling.
b. Cohort 2: non-GCB DLBCL,
with cell of origin defined by either immunohistochemistry or gene expression
profiling. Subjects who have transformed to DLBCL from another histology may be
enrolled into Cohort 3.
c. Cohort 3: Transformed lymphoid malignancy, including but
not limited to: i. Large cell transformation of chronic lymphocytic leukemia
(Richter's transformation). ii. Large cell transformation of other WHO-classified
indolent non-Hodgkin's lymphoma, including FL, or MZL.
d. Cohort 4: Histologically
confirmed PCNSL or SCNSL of breast or testicular origin: i. Must be able to tolerate
lumbar puncture and/or Ommaya taps. ii. Must have received at least 1 prior central
nervous system (CNS)-directed therapy. iii. Presence of brain parenchymal and/or
leptomeningeal disease.
2. Aged 18 years or older, able and willing to provide written informed consent and to comply
with the study protocol.
3. Measurable disease for non-Hodgkin lymphoma as defined Protocol Eligibility
4. Laboratory parameters as specified in Protocol Eligibility
5. Anticipated survival of at least 4 months.
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
7. Female subjects of childbearing potential and nonsterile males must agree to adhere to contraception methods as outlines in Protocol Eligibility

Exclusion Criteria:
1. Known, active, CNS lymphoma or leukemia, except for Cohorts 4.
2. Diagnosis with Waldenstrom's macroglobulinemia (WM).
3. For PCNSL and SCNSL (Cohorts 4): See Protocol Eligibilty for restrictions on corticosteroid therapy
4. Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenia purpura.
5. History of stroke or cerebral hemorrhage within 6 months of enrollment.
6. History of significant cardiovascular disease, as defined in Protocol Eligibility
7. Severe or debilitating pulmonary disease, as defined in Protocol Eligibility
8. History of severe allergic or anaphylactic reactions to monoclonal antibody therapy.
9. Prior BTK inhibitor or anti-PD-1/anti-PD-L1 treatment.
10. Any illness or condition that in the opinion of the investigator may affect safety of treatment or evaluation of any study endpoint.
11. Active autoimmune diseases or history of severe autoimmune diseases, as defined in Protocol Eligibility
12. A condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14 days of study drug administration, except for PCNSL and SCNSL. *See Protocol Eligibility
13. History of interstitial lung disease or noninfectious pneumonitis, except for those induced by radiation therapy.
14. Requirement for medications which strong cytochrome P450 (CYP)3A inhibitors or inducers.
15. Vaccination with a live vaccine within 28 days of the initiation of treatment.
16. A candidate for hematopoietic stem cell transplantation. Subjects are excluded if they had received an allogeneic stem cell transplantation within 6 months or have active graft-versus-host-disease requiring ongoing immunosuppression.
17. Participated in any investigational drug study within 28 days or not recovered from toxicity of any prior chemotherapy to Grade ≤ 1.
18. History of other active malignancies within 2 years of study entry, with the exception of adequately treated in-situ carcinoma of cervix; localized basal cell or squamous cell carcinoma of skin; or previous malignancy confined and treated locally (surgery or other modality) with curative intent.
19. Major surgery in the past 4 weeks prior to the first day of screening.
20. Active and symptomatic fungal, bacterial, and/or viral infection; human T-cell lymphotropic virus type 1 seropositive status.
21. See Protocol Eligibility for HIV and Hepatitis restrictions
22. Inability to comply with study procedures.
23. Pregnant or nursing women.
24. Men or women of childbearing potential who refuse to use an adequate measure of contraception, unless they have past medical history of surgical sterilization.
25. Currently taking or plan to take CNS penetrant therapy such as thiotepa, cytarabine, or partially CNS penetrant agents known to be active in lymphoid tumors, such as rituximab.
26. Has taken or plans to take any chemotherapy, immunotherapy (eg, interleukin, interferon, thymoxin), or any investigational therapies to treat leukemia or lymphoma within 28 days or 5 half-lives (whichever is shorter) of the first study drug administration, including CNS penetrating agents.

For Protocol Eligibility see: https://clinicaltrials.gov/ct2/show/NCT02795182

Contact person:

Louise Hay
Email louise.hay@health.wa.gov.au
Phone 08 6383 3207


Email
Phone

Principal Investigator:

Dr Gavin Cull

08 6457 7600

Sponsor:

BeiGene Australia

Phase:

Ib

Protocol Number:

BGB-3111/BGB-A317 Study 001

Trial Registration Number:

NCT02795182

Clinical Trials.gov

ANZ Clinical Trial Registry