Metastatic solid tumours Cancer
Conditions
Interventions
Arm A: Participants will receive inavolisib, 9 milligrams (mg), orally, once daily (QD) starting on Day 2 of Cycle 1 through the discontinuation of study treatment due to adverse events, withdrawal of
Sponsors
F. Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Participants must be at least 18 years of age at time of signing Informed Consent Form 2. For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception, and agreement to refrain from donating eggs 3. For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agreement to refrain from donating sperm 4. Incurable metastatic phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA)-wild type or PIK3CA-mutated solid tumours previously treated with multiple (=2) lines of therapy 5. For Arm A of the study: non-obese, non-diabetic participants with BMI <30 kilogram per square metre (kg/m²), fasting blood sugar (FBG) <126 milligram per decilitre (mg/dL) (7.0 mmol/L) and glycated haemoglobin (HbA1C) <5.7% at screening 6. For Arm B1 and Arm B2 of the study: Obese participants and/or prediabetic participants with BMI =30 kg/m², FBG 126-140 mg/dL (7.0-7.8 mmol/L) and HbA1C between 5.7% and <7% at screening 7. Eastern Cooperative Oncology Group (ECOG) performance status =2 8. Life expectancy of =12 weeks 9. Adequate hematologic and organ function within 14 days prior to initiation of study treatment 10. Ability, in the investigator’s judgment, and willingness to comply with all study-related procedures
Exclusion criteria
Exclusion criteria: 1. Any history of leptomeningeal disease or carcinomatous meningitis 2. Type 2 diabetes requiring ongoing systemic treatment at the time of study entry; or any history of Type 1 diabetes 3. 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 4. Inability or unwillingness to swallow pills 5. Malabsorption syndrome or other condition that would interfere with enteral absorption 6. 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 with few criteria 7. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures once per 2 weeks or more frequently 8. Serious infection requiring IV (intravenous) antibiotics within 14 days prior to Day 1 of Cycle 1 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. Participants requiring any daily supplemental oxygen 12. Symptomatic active lung disease, including pneumonitis 13. History of or active gastrointestinal inflammatory disease (e.g., Crohn’s disease or ulcerative colitis) or any active bowel inflammation (including diverticulitis) 14. Symptomatic hypercalcemia requiring continued use of bisphosphonate or denosumab therapy 15. Clinically significant and active liver disease, including severe liver impairment (Child-Pugh Class B/C), viral or other hepatitis, current alcohol abuse, or cirrhosis 16. Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness 17. 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 18. Major surgical procedure, or significant traumatic injury, within 4 weeks prior to initiation of study treatment or anticipation of the need for major surgery during study treatment 19. Minor surgical procedures <7 days prior to initiation of study treatment 20. Chemotherapy within 2 weeks or 5 half-lives, whichever is longer, prior to initiation of study treatment. Radiotherapy, or any other anti-cancer therapy within 2 weeks prior to initiation of study treatment 21. Investigational drug(s) within 4 weeks before initiation of study treatment 22. Unresolved toxicity from prior therapy, except for hot flashes, alopecia, and Grade <2 peripheral neuropathy 23. History of other malignancy within 5 years prior to screening with few exceptions 24. History of or active
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Percentage of Participants with Severity of Inavolisib Associated Hyperglycaemia as Assessed as an Adverse Event (AE) per National Cancer Institute-Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) from Pre-treatment till 30-days Post Final Dose of the Study Treatment (approximately up to 2 years) 2. Change in Blood Glucose Levels as Assessed by Laboratory Measurements at Multiple Timepoints from Pre-treatment till Day 1 of Cycle 3 3. Average Glucose over 24 hours Assessed Using Continuous Glucose Monitoring (CGM) of Participants Receiving Inavolisib in Arm A, Arm B1, and Arm B2 at Multiple Timepoints from Pre-treatment till Day 1 of Cycle 3 4. Peak Glucose over 24 hours Assessed Using CGM of Participants receiving Inavolisib in Arm A, Arm B1, and Arm B2 at Multiple Timepoints from Pre-treatment till Day 1 of Cycle 3 5. Average Glucose over 24 hours Assessed Using CGM of Participants Receiving Morning (AM) Dosing of Inavolisib Versus Evening (PM) Dosing of Inavolisib in Arm A, Arm B1, and Arm B2 at Multiple Timepoints from Pre-treatment till Day 1 of Cycle 3 6. Peak Glucose over 24 hours Assessed Using CGM of Participants Receiving Morning (AM) Dosing of Inavolisib Versus Evening (PM) Dosing of Inavolisib in Arm A, Arm B1, and Arm B2 at Multiple Timepoints from Pre-treatment till Day 1 of Cycle 3 7. Percentage of Participants with AEs from Pre-treatment till 30-days Post Final Dose of the Study Treatment (approximately up to 2 years) 8. Percentage of Participants with Severity of AEs per NCI-CTCAE v5.0 from Pre-treatment till 30-days Post Final Dose of the Study Treatment (approximately up to 2 years) 9. Maximum Observed Concentration (Cmax) of Inavolisib at Multiple Timepoints from Day 1 (Day 2 for Arm A) of Cycle 1 till Day 1 of Cycle 3 10. Area under the Concentration-time Curve from Hour 0 to the Last Measurable Concentration (AUC0-t) of Inavolisib at Multiple Timepoints from Day 1 (Day 2 for Arm A) of Cycle 1 till Day 1 of Cycle 3 | — |
Secondary
| Measure | Time frame |
|---|---|
| There are no secondary outcome measures | — |
Countries
Moldova, Romania
Contacts
Public ContactClinical Trials
Outcome results
None listed