PIK3CA-mutated solid cancers including previously treated recurrent or metastatic HNSCC Cancer
Conditions
Interventions
This is a non-randomized study and treatment assignment will be conducted with an interactive voice or Web-based response system (IxRS).
Arm A: Participants will receive inavolisib, 9 mg, orally, on
Sponsors
F. Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Participants must be at least 18 years of age 2. Histologically or cytologically confirmed recurrent and/or metastatic HNSCC that has been previously treated with systemic therapy in the recurrent and/or metastatic setting 3. Documented positive or negative human papillomavirus (HPV) status as determined locally by p16 immunohistochemistry (IHC; preferred), in situ hybridization, and/or by polymerase chain reaction-based assay. Participants with either HPV-positive or HPV-negative status are eligible ("unknown" HPV status is not eligible) 4. Eligible participants must not be suitable for treatment with surgery and/or radiation 5. Confirmation of biomarker eligibility: Valid results from either central testing of blood or local testing of blood or tumour tissue documenting PIK3CA-mutated tumour status 6. Consent to provide fresh (preferred) or archival tumour tissue specimen 7. Negative hepatitis B surface antigen (HBsAg) and total hepatitis B core antibody (HBcAb) test or positive total HBcAb test followed by a negative hepatitis B virus (HBV) DNA at screening 8. Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV RNA test at screening 9. Measurable disease per RECIST v1.1 10. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 11. Life expectancy of =12 weeks
Exclusion criteria
Exclusion criteria: 1. Prior treatment with any phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), or mammalian target of rapamycin (mTOR) inhibitor, or any agent whose mechanism of action is to inhibit the PI3K/AKT/mTOR pathway 2. Appropriate for treatment with surgery and/or radiation at the time of entry into the study, as per national or local treatment guidelines 3. Type II diabetes requiring ongoing systemic treatment at the time of study entry; or any history of Type I diabetes 4. Malabsorption syndrome or other condition that would interfere with enteral absorption 5. Known and untreated, or active central nervous system (CNS) metastases (progressing or requiring anticonvulsants or corticosteroids for symptomatic control). Participants with a history of treated CNS metastases are eligible provided they meet specified criteria 6. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures twice per week or more frequently 7. Serious infection requiring IV antibiotics within 7 days prior to Day 1 of Cycle 1 8. Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of the need for such a vaccine during study treatment 9. Any concurrent ocular or intraocular condition (e.g., cataract or diabetic retinopathy) that, in the opinion of the investigator, would require medical or surgical intervention during the study period to prevent or treat vision loss that might result from that condition 10. Active inflammatory (e.g., uveitis or vitritis) or infectious (e.g., conjunctivitis, keratitis, scleritis, or endophthalmitis) conditions in either eye or history of idiopathic or autoimmune-associated uveitis in either eye 11. Requirement for daily supplemental oxygen 12. Symptomatic active lung disease, including pneumonitis 13. History of or active inflammatory bowel disease (e.g., Crohn’s disease or ulcerative colitis) or any active bowel inflammation (including diverticulitis) 14. Known Human Immunodeficiency Virus (HIV) infection 15. Current severe, uncontrolled systemic disease (e.g., clinically significant cardiovascular, pulmonary, metabolic, or infectious disease) or any other diseases, active or uncontrolled pulmonary dysfunction, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug, that may affect the interpretation of the results, or that renders the participant at high risk from treatment complications 16. Chemotherapy, radiotherapy, or any other anti-cancer therapy within 2 weeks before enrolment 17. Investigational drug(s) within 4 weeks before enrolment 18. Unresolved toxicity from prior therapy, except for hot flashes, alopecia, and Grade = 2 peripheral neuropathy 19. History of other malignancy within 5 years prior to screening, with specified exceptions 20. History of or active clinically significant cardiovascular dysfunction 21. Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the participant's safe participation in and completion of the study) 22. Chronic corticosteroid therapy of =10 mg of prednisone per day or an equivalent dose of other anti-inflammatory corticosteroids or immunosuppressants for a chronic disease 23. Allergy or hypersensitivity to components of the inavolisib formulation 24. Treatment with strong CYP3
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Percentage of participants with select treatment-related toxicities (TRT) in Arm B as assessed by the investigator from Day 1 of Cycle 1 to Day 3 of Cycle 2 2. Percentage of participants with adverse events (AEs) and serious adverse events (SAEs) as assessed by the investigator from start of treatment until 30 days after the final dose of inavolisib or atezolizumab, or until initiation of another anti-cancer therapy, whichever occurs first (approximately up to 3 years) 3. Percentage of participants with adverse events of special interest (AESIs) as assessed by the investigator from start of treatment until 30 days after the final dose of inavolisib or atezolizumab, or until initiation of another anti-cancer therapy, whichever occurs first (approximately up to 3 years) 4. Severity of AEs, SAEs and AESIs as assessed by the investigator per National Cancer Institute-Common Terminology Criteria for Adverse Events Version 5.0 (NCI-CTCAE V5.0) from screening until up to 30 days after the final dose of study treatment or until initiation of another anti-cancer therapy, whichever occurs first (approximately up to 3 years) 5. Change from baseline in targeted vital signs measured using weight, respiratory rate, pulse rate, blood oxygenation (pulse oximetry), systolic and diastolic blood pressure, and temperature at screening, Days 1, 4, 8, and 15 of Cycle 1, Days 1 and 10 of Cycles 2 and 3, and Day 1 of subsequent cycles and treatment discontinuation (approximately up to 3 years) 6. Change from baseline in targeted clinical laboratory tests (including ECGs) assessed using blood and urine samples and 12-lead ECG recordings at multiple timepoints from screening to end of each cycle up to treatment discontinuation (approximately up to 3 years) | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Overall response rate (ORR) as determined by the investigator using Response Evaluation Criteria for Solid Tumours version 1.1 (RECIST v1.1) every 9 weeks from Day 1 of Cycle 1 during the first 2 years, and every 12 weeks thereafter until disease progression or initiation of another anti-cancer therapy whichever occurs first (approximately up to 3 years) 2. Best overall response rate (BOR) as determined by the investigator using RECIST v1.1 every 9 weeks from Day 1 of Cycle 1 during the first 2 years, and every 12 weeks thereafter until disease progression or initiation of another anti-cancer therapy whichever occurs first (approximately up to 3 years) 3. Duration of response (DOR) as determined by the investigator using RECIST v1.1, or death, whichever occurs first every 9 weeks from Day 1 of Cycle 1 during the first 2 years, and every 12 weeks thereafter until disease progression or initiation of another anti-cancer therapy whichever occurs first (approximately up to 3 years) 4. Clinical benefit rate (CBR) as determined by the investigator using RECIST v1.1 every 9 weeks from Day 1 of Cycle 1 during the first 2 years, and every 12 weeks thereafter until disease progression or initiation of another anti-cancer therapy whichever occurs first (approximately up to 3 years) 5. Progression-free survival (PFS) as determined by the investigator using RECIST v1.1, or death, whichever occurs first every 9 weeks from Day 1 of Cycle 1 During the first 2 years, and every 12 weeks thereafter until disease progression or initiation of another anti-cancer therapy whichever occurs first (approximately up to 3 years) 6. Plasma concentration of inavolisib in Arm A measured using plasma samples at predose and 3 hours post-dose on Day 1 of Cycle 1 and 2 and at Predose on Day 1 of Cycle 3 7. Area under the concentration-time curve (AUC) of inavolisib in Arm A measured using plasma samples at Predose and 3 hours post-dose on Day 1 of Cycle 1 and 2 and at Predose on Day 1 of Cycle 3 8 | — |
Countries
Canada, France, Spain, United Kingdom, United States of America
Contacts
Public ContactClinical Trials
Outcome results
None listed