Advanced ovarian cancer, triple negative breast cancer Cancer Malignant neoplasm of breast, malignant neoplasm of ovary
Conditions
Interventions
Group 1 (Escalation Dose: RO6870810 + Atezolizumab) participants will be administered escalating doses of RO6870810 (0.3 mg/kg, 0.45 mg/kg, and 0.65 mg/kg) subcutaneously (SC) once daily (QD) during t
Sponsors
Genentech, Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Groups 1 and 2: 1. Histologically confirmed advanced ovarian cancer or triple negative breast cancer who in the opinion of the Investigator are appropriate for this study 2. Received prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies, provided the following requirements are met: 2.1. Minimum of 5 months from the last dose of anti-PD-1, anti-CTLA-4, anti-PD- L1, or CD137 agonist treatment 2.2. No history of severe immune-related adverse effects from CD137 agonist, anti-CTLA-4, anti-PD-1, or anti-PD-L1 (NCI CTCAE Grade 3 and 4). Any toxicity related to the therapy must have resolved completely, no residual toxicity as assessed by NCI CTCAE (v4.03) 2.3. Agree to use protocol defined methods of contraception For all participants, the reliability of sexual abstinence must be evaluated in relation to the duration of the clinical study and the preferred and usual lifestyle of the participant. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or post-ovulation methods) and withdrawal are not acceptable methods of contraception Group 3: 1. Histologically confirmed triple negative breast cancer 2. Received either one or 2 prior systemic treatments for metastatic breast cancer 3. Documented disease progression on or after the most recent treatment Group 4: 1. Recurrent ovarian cancer 2. Received no more than two prior lines of platinum therapy in the recurrent setting and have progressed within 9 months from the last platinum containing regimen All participants: 1. Measurable disease by RECIST criteria version 1.1 prior to study drug administration 2. Performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale 3. Life expectancy, in the opinion of the Investigator, of at least 3 months 4. Disease-free of active second/secondary or prior malignancies for =2 years with the exception of squamous cell carcinoma of the skin, or carcinoma in situ of the cervix or breast 5. Willing to provide the protocol specified tumor biopsies 6. Acceptable hematologic status, liver and renal function
Exclusion criteria
Exclusion criteria: 1. History of prior malignancy except solid tumor treated curatively more than 3 years ago without evidence of recurrence 2. Asymptomatic or symptomatic, untreated, or actively progressing central nervous system (CNS) metastases 3. History of leptomeningeal disease 4. Uncontrolled tumor-related pain 5. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures. Participants with indwelling catheters are allowed. 6. Uncontrolled or symptomatic hypercalcemia 7. New York Heart Association Class III or IV cardiac disease, pericarditis, myocardial infarction within the past 6 months, unstable arrhythmia 8. Fredericia-corrected QT interval (QTcF) >470 msec (female) or >450 msec (male), or history of congenital long QT syndrome. Any electrocardiogram (ECG) abnormality, including pericarditis, which in the opinion of the investigator would preclude safe participation in the study. 9. Active, uncontrolled bacterial, viral, or fungal infections within 7 days of study entry requiring systemic therapy. Participants with active TB infection are excluded from the study. 10.Known clinically important respiratory impairment 11. History of major organ transplant 12. History of an autologous or allogeneic bone marrow transplant 13. Serious non-malignant disease that could compromise protocol objectives in the opinion of the Investigator and/or the Sponsor 14. Pregnant or nursing women 15. Any systemic anticancer therapy within 3 weeks prior to Cycle 1 Day 1 16. Any radiation treatment to metastatic site within =14 days of Cycle 1 Day 1 17. Major surgical procedure, open biopsy, or significant traumatic injury within 30 days prior to Cycle 1 Day 1 or anticipation of the need for major surgical procedure during the course of the study 18. History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric, human or humanized antibodies or fusion proteins 19. Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation 20. Active or history of autoimmune disease 21. History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis on screening chest computed tomography (CT) scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted. 22. Positive test for Human immunodeficiency virus (HIV) 23. Active hepatitis B or hepatitis C 24. Receipt of a live, attenuated vaccine within 4 weeks prior to randomization or anticipation that such a live, attenuated vaccine will be required during the study 25. Treatment with an investigational therapy within 28 days prior to initiation of study treatment 26. Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment 27. Consumption of agents which strongly inhibit CYP3A4 enzyme, within 7 days prior to the first dose of study treatment
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Dose Limiting Toxicities (DLT) in group 1 participants measured using the reported safety data between baseline and 21 days (first cycle) and within the participant receives the full intended combination doses and number of administrations. No statistical analyses have been performed as this was a 3+3 design. 2. Adverse Events (AEs) in all participants graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v4.03) between baseline and 22 months 3. Change in Vital Signs, Physical Findings, Electrocardiogram (ECG) and Laboratory Parameters in all participants measured using patient and laboratory data between baseline and 22 months. No statistical analyses have been performed as this was 3+3 design. 4. Objective Response (OR) in group 3 and 4 participants as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 between the first occurrence of objective response and either disease progression, death from any cause, or 22 months | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Maximum concentration (Cmax) of RO6870810 and atezolizumab measured using serum samples taken at pre-dose on day 1; pre-dose and 0.25, 0.5, 1, 2, 4, 6, 8, and 10 h on day 14; 24 and 28 h on day 15; and pre-dose on day 21 of cycle 1 and all even cycles until the end of treatment for RO6870810; and at pre-dose and end of infusion on day 1 of cycle 1; pre-dose on day 1 of all even cycles; and 22 months for atezolizumab 2. Time of maximum concentration (tmax) of RO6870810 and atezolizumabmeasured using serum samples taken at pre-dose on day 1; pre-dose and 0.25, 0.5, 1, 2, 4, 6, 8, and 10 h on day 14; 24 and 28 h on day 15; and pre-dose on day 21 of cycle 1 and all even cycles until the end of treatment for RO6870810; and at pre-dose and end of infusion on day 1 of cycle 1; pre-dose on day 1 of all even cycles; and 22 months for atezolizumab 3. Clearance (CL) or Apparent Clearance (CL/F) of RO6870810 and atezolizumab measured using serum samples taken at pre-dose on day 1; pre-dose and 0.25, 0.5, 1, 2, 4, 6, 8, and 10 h on day 14; 24 and 28 h on day 15; and pre-dose on day 21 of cycle 1 and all even cycles until the end of treatment for RO6870810; and at pre-dose and end of infusion on day 1 of cycle 1; pre-dose on day 1 of all even cycles; and 22 months for atezolizumab 4. Volume of Distribution (Vd) or Apparent Volume of Distribution (Vd/F) of RO6870810 and atezolizumab measured using serum samples taken at pre-dose on day 1; pre-dose and 0.25, 0.5, 1, 2, 4, 6, 8, and 10 h on day 14; 24 and 28 h on day 15; and pre-dose on day 21 of cycle 1 and all even cycles until the end of treatment for RO6870810; and at pre-dose and end of infusion on day 1 of cycle 1; pre-dose on day 1 of all even cycles; and 22 months for atezolizumab 5. Area under the plasma concentration-time curve from time zero to end of the dosing interval (AUC0-tau) of RO6870810 and atezolizumab measured using serum samples taken at pre-do | — |
Countries
Australia, Canada, Denmark, England, Scotland, United Kingdom, United States of America
Contacts
Public ContactClinical Trials
Outcome results
None listed