Metastatic solid tumor Cancer Metastatic solid tumor
Conditions
Interventions
This open-label, two-part study is designed to assess the safety, PK, PD, and therapeutic activity of selicrelumab in combination with vanucizumab or bevacizumab in participants with metastatic solid
Sponsors
Genentech, Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Part I (dose escalation): 1. Histologically confirmed advanced/metastatic solid tumor (except prostate cancer and squamous non-small cell lung cancer [NSCLC]) Part II (expansion): 1. Histologically confirmed advanced/metastatic platinum-resistant ovarian carcinoma (aPROC), head and neck squamous cell carcinoma (HNSCC), or non-squamous NSCLC previously treated with anti-PD-L1/PD-1 inhibitor alone or in combination (e.g. atezolizumab, nivolumab, pembrolizumab, durvalumab, avelumab) 2. Checkpoint inhibitor (CPI)- experienced patients must have experienced documented disease progression on or after PD-L1/PD-1 inhibitor therapy 3. In CPI-experienced patients, the PD-L1/PD-1 inhibitor must have been part of the most recent systemic anticancer therapy administered prior to study enrollment 4. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 5. Life expectancy =16 weeks 6. Adequate hematologic, renal, hepatic, and cardiovascular function 7. Measurable disease per Response Evaluation Criteria in Solid Tumors, v 1.1 (RECIST v1.1) 8. Tumors must be acceptable for biopsy. Participants in part II may be enrolled without a biopsy if the collection is not clinically feasible. 9. Agreement to use adequate contraceptive measures among men or among women of childbearing potential
Exclusion criteria
Exclusion criteria: Part I (dose escalation): 1. Prostate cancer or squamous NSCLC 2. Recent systemic anti-cancer treatment 3. Prior treatment with anti-programmed death (PD) 1 or anti-programmed death ligand (PD-L) 1 therapeutic antibody, vanucizumab, or compounds targeting cluster of differentiation (CD) 40 less than 4 weeks or 5xt1/2 (whichever is shorter) prior to enrollment Part II (expansion): 1. Treatment targeting vascular endothelial growth factor (VEGF) or receptor within 12 months prior to enrollment 2. Systemic immunosuppressive medication within 2 weeks prior to day 1 of cycle 1 3. Chronic daily treatment with non-steroidal anti-inflammatory drugs 4. Unacceptable/unresolved toxicity from prior anti-cancer therapy 5. Patients who have had a surgical procedure or significant traumatic injury within 28 days prior to initiation of study treatment, or a core biopsy or other minor surgical procedure within 7 days prior to initiation of study treatment 6. Bisphosphonate therapy for symptomatic hypercalcemia 7. Significant vascular disease 8. History of hypertensive crisis or hypertensive encephalopathy 9. Current or recent use of aspirin (>325 mg/day) or clopidogrel (>75 mg/day) 10. History of vein thrombosis/thromboembolism, or use of anticoagulants within 7 days prior to study drug 11. Primary tumor in place in participants with colorectal cancer, or evidence of bowel involvement (metastasis, direct tumor invasion) in participants with other non-gastrointestinal cancer 12. Significant cardiovascular or cerebrovascular disease within 6 months prior to D1 of C1 13. History of fistula, bowel obstruction, perforation, or abscess 14. Prior radiotherapy to pelvis or abdomen, recto-sigmoid involvement, or bowel involvement among participants with aPROC 15. Severe non-healing wound, active ulcer, or untreated bone fracture 16. Pregnant or lactating women 17. History of autoimmune disease 18. Human immunodeficiency virus (HIV) or hepatitis B or C 19. Severe infection or receipt of a live/attenuated vaccine within 4 weeks prior to D1 of C1 20. Other significant malignancies within 3 years prior to D1 of C1 21. Allergy/hypersensitivity to study drug 22. Prior allogeneic bone marrow or solid organ transplant 23. Other conditions/findings that may contraindicate the use of study drug 24. Major surgery within 4 weeks prior to study drug 25. Known clinically significant liver disease 26. History of hemoptysis or bleeding diathesis, or known coagulopathies 27. Known symptomatic or untreated central nervous system (CNS) malignancy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Part I (dose escalation): 1. Percentage of participants With Dose-Limiting Toxicities (DLTs) measured using the National Cancer Institute-Common Terminology Criteria for Adverse Events version 4.03 (NCI-CTCAE v 4.03) between 1 and 28 days. DLTs will be defined as an adverse event or abnormal laboratory value, (judged clinically significant by the investigator) considered related to selicrelumab and/or vanucizumab that occurrs during the first 28 days of treatment. 2. Maximum Tolerated Dose (MTD) of selicrelumab in combination with vanucizumab measured using the National Cancer Institute-Common Terminology Criteria for Adverse Events version 4.03 (NCI-CTCAE v 4.03) between 1 and 28 days. MTD will be defined as the dose level for which the probability of DLT (as defined above) was equal to a protocol-specified target probability. 3. Recommended Phase II Dose (RP2D) of selicrelumab in combination with vanucizumab calculated from the MTD (as defined above) which was measured between 1 and 28 days 4. Percentage of participants with Anti-Drug Antibodies (ADAs) to vanucizumab measured from serum samples taken predose (within 10 min before infusion) on day 1 of cycles 1, 2, 4, and every 2 cycles until disease progression and/or 45 days after the last dose (up to approximately 42 months). Parts I (dose escalation) and II (expansion): 1. Percentage of Participants With Adverse Events (AEs) measured between day 1 and treatment discontinuation and/or safety follow up visit (45 days post-last dose, up to approximately 42 months). An AE will be defined as any untoward medical occurrence in a participant who received a pharmaceutical product, and which did not necessarily have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. | — |
Secondary
| Measure | Time frame |
|---|---|
| Part I (dose escalation): 1. Overall Response Rate (ORR) measured using local protocol for oncological imaging and evaluated using the Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Criteria during tumor assessments at baseline and on day 1 of cycle 3, 5, and 7, and every 12 weeks thereafter, until disease progression until the first documentation of a complete or partial response, or participant's discontinuation or death, whichever occurs first (up to approximately 42 months). The ORR will be defined as the percentage of participants with confirmed complete response (disappearance of all target lesions) and partial response (at least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters) on two consecutive occasions =4 weeks apart, as determined by the investigator. 2. Duration of Objective Response (DOR) measured using local protocol for oncological imaging and evaluated using the RECIST v1.1 Criteria during tumor assessments at baseline and on day 1 of cycle 3, 5, and 7, and every 12 weeks thereafter, until disease progression until the first documentation of a complete or partial response, or participant's discontinuation or death, whichever occurs first (up to approximately 42 months). DOR will be defined as the time from the first occurrence of a documented objective response to the time of relapse or death from any cause, and will be analysed in participants who have a best overall response of either a complete or partial response. 3. Disease control rate (DCR) measured using local protocol for oncological imaging and evaluated using the RECIST v1.1 Criteria during tumor assessments at baseline and on day 1 of cycle 3, 5, and 7, and every 12 weeks thereafter, until disease progression until the first documentation of a complete or partial response, or participant's discontinuation or death, whichever occurs first (up to approximately 42 months). DCR will be defined as the per | — |
Countries
Belgium, Canada, Denmark, Italy, Netherlands, Spain, United States of America
Contacts
Public ContactClinical Trials
Outcome results
None listed