©2022 Stanford Medicine
A Study of RO6958688 in Participants With Locally Advanced and/or Metastatic Carcinoembryonic Antigen Positive Solid Tumors
Not Recruiting
Trial ID: NCT02324257
Purpose
Study BP29541 is a first-in-human, open-label, multi-center, dose-escalation Phase I clinical
study of single-agent RO6958688 in participants with locally advanced and/or metastatic
carcinoembryonic antigen (CEA) positive solid tumors who have progressed on standard
treatment, are intolerant to standard of care (SOC), and/or are non-amenable to SOC. The
study will be conducted in two parts. Part I of the study will investigate the safety and
pharmacokinetics of a single dose of RO6958688 in single participant cohorts with dosing
starting from a minimal anticipated biological effect level dose of 0.05 milligrams (mg) and
up to a maximum dose of 2.5 mg. Part II will establish the appropriate therapeutic dose based
on safety, pharmacokinetics, and the maximum tolerated dose (MTD) of RO6958688 for the once
per week (QW) regimen, every three weeks (Q3W) regimen, and for the step up dosing regimen.
Official Title
An Open-Label, Multicenter, Dose-Escalation Phase I Study to Evaluate the Safety, Pharmacokinetics, and Therapeutic Activity of RO6958688, A Novel T-cell Bispecific Antibody That Targets the Human Carcinoembryonic Antigen (CEA) on Tumor Cells and CD3 on T Cells, Administered Intravenously in Patients With Locally Advanced and/or Metastatic CEA(+) Solid Tumors
Stanford Investigator(s)
George A. Fisher Jr.
Colleen Haas Chair in the School of Medicine
Tyler Johnson
Clinical Assistant Professor, Medicine - Oncology
Hans-Christoph Becker, MD, FSABI, FSCCT
Clinical Professor, Radiology
Eligibility
Inclusion Criteria:
- For dose escalation, locally advanced and/or metastatic gastrointestinal (GI) solid
tumor in participants who have progressed on a standard therapy, are intolerant to
SOC, and/or are non-amenable to SOC and other solid tumors expressing CEA. Only
locally advanced and/or metastatic colorectal cancer participants should be included
in the scheduled comparison expansion
- Radiologically measurable disease according to RECIST v1.1
- Life expectancy, in the opinion of the investigator of greater than or equal (>/=) to
12 weeks and LDH= 2.5 x ULN
- Eastern Cooperative Oncology Group Performance Status of 0-1
- All acute toxic effects of any prior radiotherapy, chemotherapy, or surgical procedure
must have resolved to Grade less than or equal to 1 or returned to baseline except
alopecia (any grade) and Grade 2 peripheral neuropathy
- Adequate hematological, liver, and renal function
- Participants must agree to remain abstinent or be willing to use effective methods of
contraception as defined in the protocol
- Non-GI solid tumors (like non-small cell lung cancer or breast cancer) should have
confirmed CEA expression in tumor tissue >/= 20% of tumor cells staining with at least
moderate to high intensity of CEA expression are required (immunohistochemistry
[IHC]2+ and IHC 3+). For CRC, pancreatic and gastric cancer participants, the CEA
assessment will be performed retrospectively and the result is not needed to enroll
the participant
Exclusion Criteria:
- Participants with a history or clinical evidence of central nervous system primary
tumors or metastases including leptomeningeal metastases unless they have been
previously treated, are asymptomatic, and have had no requirement for steroids or
enzyme-inducing anticonvulsants in the last 14 days before screening
- Spinal cord compression not definitively treated with surgery and/or radiation or
previously diagnosed and treated spinal cord compression without evidence that disease
has been clinically stable for at least 2 weeks prior to enrollment
- Leptomeningeal disease
- Participants with paraspinal, paratracheal and mediastinal pathologic lesions larger
than 2 centimeters unless they are previously irradiated. Irradiation of lesions must
be completed at least 14 days prior to initiation of study treatment
- Participants with another invasive malignancy in the last 2 years (with the exception
of basal cell carcinoma and tumors deemed by the investigator to be of low likelihood
for recurrence)
- Evidence of significant, uncontrolled concomitant diseases that could affect
compliance with the protocol or interpretation of results or contraindicate the use of
an investigational drug, including diabetes mellitus, history of relevant
cardio-pulmonary disorders, and known autoimmune diseases
- Participants with bilateral lung lesions and dyspnea and/or with bilateral lung
lesions and an oxygen saturation (SaO2) level less than 92% or participants with
lobectomy or pneumonectomy with lung metastases in the remaining lung and either
dyspnea or SaO2 less than 92% at baseline
- Uncontrolled hypertension (systolic blood pressure [BP] greater than [>] 150
millimeters of mercury [mmHg] and/or diastolic BP > 100 mmHg), unstable angina,
congestive heart failure of any New York Heart Association classification, serious
cardiac arrhythmia that requires treatment with the exceptions of atrial fibrillation
and paroxysmal supraventricular tachycardia, and history of myocardial infarction
within 6 months of enrollment
- Active or uncontrolled infections
- Known human immunodeficiency virus (HIV) or known active hepatitis B or hepatitis C
infection for participants not receiving obinutuzumab pretreatment
- Known HIV (HIV testing will be performed at screening if required by local
regulations) in participants to be pretreated with obinutuzumab
- Pregnant or breastfeeding women
- Known hypersensitivity to any of the components of RO6958688 and/or obinutuzumab
- Concurrent therapy with any other investigational drug
- Last dose of any chemotherapy less than 28 days prior to the first RO6958688 infusion
- Expected need for regular immunosuppressive therapy
- Regular dose of corticosteroids the 28 days prior to Day 1 of this study or
anticipated need for corticosteroids that exceeds prednisone 10 mg/day or equivalent
within 28 days prior to the first RO6958688 infusion. Inhaled and topical steroids are
permitted
- Radiotherapy within the last 28 days prior to the first RO6958688 infusion with the
exception of limited-field palliative radiotherapy.
Additional Exclusion Criteria for Participants to be Pretreated with Obinutuzumab:
- Positive test results for human T-lymphotropic virus 1 (HTLV-1) or active HIV
infection
- Positive test results for chronic hepatitis B infection or hepatitis C
- Known active tuberculosis (TB) requiring treatment within 3 years prior to baseline or
latent TB that has not been appropriately treated
- Active bacterial, viral, fungal, or other infection, or any major episode of infection
requiring treatment with intravenous (IV) antibiotics within 4 weeks of Cycle 1, Day 1
- Known hypersensitivity to any of the components of obinutuzumab; hypersensitivity to
Chinese hamster ovary cell products or other recombinant human antibodies
- History of progressive multifocal leukoencephalopathy (PML)
Intervention(s):
drug: RO6958688
drug: Obinutuzumab
drug: Tocilizumab
Not Recruiting
Contact Information
Stanford University
School of Medicine
300 Pasteur Drive
Stanford,
CA
94305
CCTO
650-498-7061