Cancer
Conditions
Interventions
Single Agent GDC6036
dose expansion stage
Sponsors
Genentech Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: ? Signed Informed Consent Form ? Age =18 years at time of signing Informed Consent Form ? Ability to comply with the study protocol, in the investigator’s judgment ? Evaluable or measurable disease per RECIST v1.1 ? Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 ? Life expectancy of =12 weeks ? Adequate hematologic and organ function within 14 days prior to initiation of study treatment, defined by the following: ? Absolute neutrophil count =1200/µL ? Hemoglobin =9 g/dL ? Platelet count =100,000/µL ? Total bilirubin =1.5 x ULN ? Serum albumin =2.5 g/dL ? AST and ALT=2.5 x ULN with the following exception: Patients with documented liver metastases may have AST and/or ALT =5.0 x ULN. ? For women of childbearing potential: Agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception, and agreement to refrain from donating eggs, as defined below: Women must remain abstinent or use contraceptive methods with a failure rate of < 1% per year and must refrain from donating eggs during the treatment period and after the final dose of study treatment for at least: ? 6 months for GDC-6036 ? 5 months for atezolizumab (Arm B) ? 2 months for cetuximab (Arm C) ? 6 months for bevacizumab (Arm D) ? 2 weeks for erlotinib (Arm E) ? 6 months for GDC-1971 (Arm F)
Exclusion criteria
Exclusion criteria: ? Inability or unwillingness to swallow pills ? Inability to comply with study and follow-up procedures ? Malabsorption syndrome or other condition that would interfere with enteral absorption ? Known and untreated, or active central nervous system (CNS) metastases (progressing or requiring anticonvulsants or corticosteroids for symptomatic control) Patients with a history of treated CNS metastases are eligible, provided they meet all of the following criteria: - Measurable or evaluable disease outside the CNS - No history of intracranial hemorrhage or spinal cord hemorrhage - No ongoing requirement for corticosteroids as therapy for CNS metastases, with corticosteroids discontinued for ? 2 weeks prior to enrollment and no ongoing symptoms attributed to CNS metastases - No stereotactic radiation within 7 days or whole-brain radiation within 14 days prior to Day 1 of Cycle 1 - No evidence of interim progression between the completion of CNS-directed therapy and the screening radiographic study - Note: Patients with new asymptomatic CNS metastases detected at screening are eligible for the study after receiving radiotherapy and/or surgery. Following treatment, these patients may be eligible without the need to repeat the additional brain scan, if all other criteria are met. ? Leptomeningeal disease or carcinomatous meningitis ? Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures biweekly or more frequently Indwelling pleural or abdominal catheters may be allowed, provided the patient has adequately recovered from the procedure, is hemodynamically stable and symptomatically improved, and after discussion with the Medical Monitor.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The safety objective for this study is to evaluate the safety of GDC-6036 as a single agent and in combination with other anti-cancer therapies on the basis of the following endpoints: ? Incidence and severity of adverse events, with severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) ? Incidence and nature of dose-limiting toxicities (DLTs) ? Change from baseline in targeted vital signs ? Change from baseline in targeted clinical laboratory test results ? Change from baseline in targeted ECG parameters | — |
Secondary
| Measure | Time frame |
|---|---|
| The pharmacokinetic (PK) objectives for this study are to characterize the PK profile of GDC-6036 when administered as a single agent and in combination with other anti-cancer therapies and to characterize the PK profile of these anti-cancer therapies when administered in combination with GDC-6036, on the basis of the following endpoints: ? Plasma concentrations of GDC-6036, erlotinib, and GDC-1971 at specified timepoints ? Serum concentrations of atezolizumab, cetuximab, and bevacizumab at specified timepoints The exploratory PK objectives for this study are as follows: ? To evaluate potential relationships between drug exposure and the safety and activity of GDC-6036 as a single agent and in combination with other anti-cancer therapies ? To evaluate the exposure of potential circulating metabolite of GDC-6036 following a single or repeat oral dose(s) of GDC-6036 as a single agent or in combination with other anti-cancer therapies ? To assess ex vivo plasma protein binding of GDC-6036 and its impact on pharmacokinetics (Arm A only) ? To evaluate the effect of GDC-6036 on plasma levels of 4b-hydroxy cholesterol, an endogenous biomarker of CYP3A4 induction (Arm A only) ? To evaluate the effect of a standard meal taken within 30 minutes of a GDC-6036 oral dose on the pharmacokinetics of GDC-6036 (Arm A only) ? To assess potential relationships between drug exposures and the safety and activity of GDC-1971 in combination with GDC-6036;The exploratory immunogenicity objective for this study is to evaluate the immune response to study biotherapeutics on the basis of the following endpoints: ? Prevalence of anti-drug antibodies (ADAs) at baseline and incidence of ADAs after initiation of study treatment ? Evaluation of safety, efficacy, PD, and PK endpoints by ADA status ;The activity objective for this study is to make a preliminary assessment of the activity of GDC-6036 as a single agent and in combination with other anti-cancer therapies on | — |
Countries
Kenya
Contacts
Public ContactAsim Shaikh
Sub investigator
Outcome results
None listed