©2022 Stanford Medicine
A Study to Evaluate Safety, Pharmacokinetics, and Clinical Activity of Combination of RO6870810 and Venetoclax, With or Without Rituximab, in Participants With Relapsed/Refractory DLBCL and/or High-Grade B-Cell Lymphoma and/or High Grade B-Cell Lymphoma With MYC and/or BCL2 and/or BCL6
Trial ID: NCT03255096
The purpose of this study is to evaluate the safety, tolerability and clinical activity of RO6870810 in combination with venetoclax and when co-administered with rituximab in participants with relapse/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) and/or high-grade B-cell lymphoma with myelocytomatosis oncogene (MYC) and/or B-cell lymphoma 2 (BCL2) and/or B-cell lymphoma 6 (BCL6) gene rearrangements (HGBL-DH/TH).
Open-Label, Dose Escalation/Expansion Phase Ib Study to Evaluate the Safety, Pharmacokinetics, and Clinical Activity of the Combination of RO6870810 and Venetoclax, With or Without Rituximab, in Patients With Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL) and/or High-Grade B-Cell Lymphoma With MYC and/or BCL2 and/or BCL6 Gene Rearrangements
- Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2.
- Life expectancy >3 months as per investigator's assessment.
- Part 1 and Part 2 Group 1: Participantts with diffuse large B-cell lymphoma (DLBCL)
relapsed or refractory to ≥ 1 course of chemotherapy including an anti-CD20 monoclonal
antibody, and not eligible for autologous stem cell transplantation (ASCT) (including
due to chemorefractory disease). Participants with transformed FL are eligible,
provided DLBCL or HGBL-DH/TH histology is biopsy-confirmed prior to study entry and a
treatment regimen as described above has been administered. The Sponsor retains the
option to limit the number of participants enrolled with transformed FL.
Part 2, Group 2: Patients identified with DE-DLBCL (expression MYC ≥40%, BCL2 > 50%) and or
HGBL-DH/TH, relapsed or refractory to >= 1 course of chemotherapy including an anti-CD20
monoclonal antibody, and not eligible for ASCT (including due to chemorefractory disease).
Patients with transformed follicular lymphoma (FL) are eligible, provided DE-DLBCL and/or
HGBL-DH/TH histology is biopsy-confirmed prior to study entry and a treatment regimen as
described above has been administered. The Sponsor retains the option to limit the number
of participants enrolled with transformed FL.
- Part 1 and Part 2: Willing to provide the protocol specified tumor biopsy(ies): at
screening a fresh biopsy (if no archival biopsy tissue of less than 3 months prior to
treatment and without intercurrent treatment is available); Part 2: Willing to provide
an additional biopsy on Cycle 2 Day 15 (+ 2 days).
- Acceptable liver function, as specified below:
- Total bilirubin ≤ 2 times upper limit of normal (ULN). (Participants with known
Gilbert's disease who has serum bilirubin ≤ 3 × ULN may be enrolled).
- Aspartate transaminase (AST; SGOT), alanine transaminase (ALT; SGPT) ≤ 2.5 × ULN,
(or ≤ 5 × ULN if tumor involvement (liver) is present).
- Gamma-glutamyl transferase (GGT) alkaline phosphatase ≤ 2.5 × ULN.
- Acceptable renal function, as specified below:
• Creatinine clearance (CrCl) calculated by Cockroft-Gault formula of ≥ 60 mL/min.
- Acceptable hematologic status (growth factors cannot be used within the previous 7
days), as specified below:
- Absolute neutrophil count (ANC) ≥ 1000 cells/μL
- Hemoglobin ≥ 9 g/dL
- Platelet count ≥ 75,000 (platelets/μL)
- Uncontrolled symptomatic hypercalcemia.
- Acceptable coagulation status, as specified below:
- Prothrombin time (PT) and partial thromboplastin time (PTT) ≤ 1.2 × ULN (unless
receiving anticoagulation therapy, if receiving anticoagulation therapy,
eligibility will be based upon international normalized ratio [INR]).
- INR ≤ 1.6 (unless receiving anticoagulation therapy).
- If receiving warfarin: INR ≤ 3.0 and no active bleeding (i.e., no bleeding within
14 days prior to first dose of study therapy).
- Acceptable method of contraception
- Current central nervous system (CNS) lymphoma or leptomeningeal infiltration.
- New York Heart Association (NYHA) Class III or IV cardiac disease, myocardial
infarction, within the past 6 months, unstable arrhythmia, or known pericardial
- Fredericia-corrected QT interval (QTcF) >470 msec (female) or >450 msec (male), or
history of congenital long QT syndrome.
- Any electrocardiogram (ECG) abnormality, which in the opinion of the Investigator
would preclude safe participation in the study.
- Active, uncontrolled bacterial, viral, or fungal infections, within 7 days of study
entry requiring systemic therapy.
- Clinically important respiratory impairment
- Grade ≥ 3 sensory or motor neuropathy.
- Any Grade >1 (according to the NCI CTCAE 4.03) adverse reaction unresolved from
previous treatments and not readily managed and controlled with supportive care.
- Serious non-malignant disease that could compromise protocol objectives in the opinion
of the Investigator and/or the Sponsor.
- History of progressive multifocal leukoencephalopathy (PML).
- History of other malignancy within 2 years prior to screening, except for ductal
carcinoma in situ not requiring chemotherapy, appropriately treated carcinoma in situ
of the cervix, non-melanoma skin carcinoma, low-grade, localized prostate cancer
(Gleason score ≤ 7) not requiring treatment or appropriately treated Stage I uterine
- Completion of ASCT within 100 days prior to Day 1 of Cycle1.
- Prior standard or investigational anti-cancer therapy, as specified below:
- Radio-immunoconjugate 4 weeks or 5 half-lives, whichever is longer prior to Day 1
of Cycle 1.
- Monoclonal antibody or antibody-drug conjugate (ADC) therapy within 3 weeks prior
to Day 1 of Cycle 1.
- Radiotherapy, chemotherapy, or targeted small-molecule therapy within 2 weeks
prior to Day 1 of Cycle 1.
- CAR T-cell therapy 30 days prior to Day 1 of Cycle 1.
- History of major solid organ transplant (i.e., heart, lungs, liver and kidney).
- History of an allogeneic bone marrow transplant.
- Major surgical procedure within 28 days prior to Day 1 of Cycle 1.
- Treatment with systemic corticosteroids ≥ 20 mg/day prednisone or equivalent, for
non-lymphoma treatment reasons. For lower acceptable doses, documentation of a stable
dose for at least 4 weeks prior to Day 1 of Cycle 1 is required.
18. Treatment with strong to moderate CYP3A inhibitors or moderate CYP3A inducers
within 7 days prior to the first dose of study treatment.
- Treatment with strong CYP3A inducers within 14 days prior to the first dose of study
treatment of RO6870810/venetoclax.
- Consumption of grapefruits, grapefruit products, Seville oranges (including marmalade
that contains Seville oranges), or star fruit within 3 days prior to the first dose of
- Participants who are currently receiving any other investigational agent ((other than
anti-cancer therapy as specified in exclusion criteria number 13) or have received an
investigational agent within 30 days or 5 half-lives prior to Day 1 of Cycle 1,
whichever is longer.
- Prior treatment with small molecule bromodomain and extra terminal (BET) family
- Known to be human immunodeficiency virus (HIV) positive.
- Presence of positive test results for hepatitis B surface antigen (HBsAg) or hepatitis
C antibodies (HcAb) (for participants receiving regimen including rituximab)
- Pregnant or breastfeeding female.
- Significant allergy to a biological pharmaceutical therapy that, in the opinion of the
Investigator, poses an increased risk to the participant.
- Uncontrolled cancer pain. Participants requiring pain medication must be on a stable
regimen at study entry. Symptomatic lesions amenable to palliative radiotherapy should
be treated prior to enrollment.
- History of severe allergic or anaphylactic reaction to humanized or murine monoclonal
antibodies (for participants receiving regimen including rituximab).
- Known sensitivity or allergy to murine products or any component of RO6870810,
venetoclax, or rituximab.
School of Medicine
300 Pasteur Drive
Stanford, CA 94305