A study to evaluate the safety, tolerability, processing by the body, and antitumor activity of inavolisib and paclitaxel with or without targeted therapies

Who can participate?
Part 1, Arm A: Patients aged 18 years and over with locally advanced or metastatic solid tumors
Part 2, Arm A: Patients aged 18 years and over with locally advanced or metastatic PIK3CA-mutated cancer
Part 2, Arm B: Patients aged 18 years and over with locally advanced or metastatic PIK3CA-mutated, HER2-positive breast cancer

What does the study involve?
Up to 120 patients at various hospital locations around the world will take part in this study. The study is divided into two parts. Part 1, Arm A is the dose-escalation (dose-finding) part of the study. Part 2 consists of Arm A and Arm B, which will be treatment expansions after dose-finding is complete.
Part 1, Arm A: inavolisib will be tested at different doses and schedules in combination with paclitaxel in up to 24 patients with locally advanced or metastatic cancer
Part 2, Arm A: a dose and schedule of inavolisib determined to be safe in Part 1, Arm A will be tested in combination with paclitaxel, in about 76 patients with locally advanced or metastatic PIK3CA mutated (altered gene) cancer
Part 2, Arm B: a dose and schedule of inavolisib determined to be safe in Part 1, Arm A will be tested in combination with paclitaxel, trastuzumab and pertuzumab in about 20 patients with locally advanced or metastatic PIK3CA-mutated (altered gene) HER2-positive breast cancer
Patients will have the following assessments and measurements:
1. Vital signs - temperature, pulse rate, blood pressure, breathing rate and oxygen level
2. Complete or limited physical exam
3. Assessment of performance status
4. Electrocardiogram (ECG): measuring the electrical activity of the heart
5. Urine sample for standard laboratory tests
6. Blood samples for standard laboratory tests and to measure study treatment levels (pharmacokinetics)
7. Tumor tissue samples (biopsies)
8. Tumor assessments: scans of the internal organs and bones that may include a computed tomography (CT) scan, a magnetic resonance imaging (MRI) scan, or a bone scan
9. Eye examination

What are the possible benefits and risks of participating?
The patient's cancer and health may or may not improve in this study, but the information collected may help other people who have a similar medical condition in the future.
High blood sugar, oral inflammation/ulcers, rash, and diarrhea/colitis (colon inflammation) are identified risks for inavolisib. Pneumonitis (lung inflammation), immunosuppressant effects, reproductive effects, eye toxicities, and embryo-fetal toxicities are potential risks for inavolisib. Results to date have shown good tolerability, with no additional safety concerns beyond those associated with expected toxicities. Paclitaxel is known to cause bone marrow suppression, hypersensitivity reactions, joint or muscle pain, oral inflammation/ulcers, nerve damage, alopecia (hair loss), injection site reactions, and vascular (blood vessel) disorders. Administration-related reactions/allergic-like reactions/hypersensitivity, pulmonary events, and stage B heart failure are identified risks for trastuzumab. Allergic reactions, administration-related reactions, stage B heart failure, and Epidermal Growth Factor Receptor (EGFR)-related toxicities, which include diarrhea, rash/skin reactions and mucositis (inflammation in the mouth or gut) are identified risks for pertuzumab. Oligohydramnios (amniotic fluid volume that is less than expected) is also a potential risk for both trastuzumab and pertuzumab.
Given that these risks may require either dose interruptions and/or dose reductions or may have the potential to cause life-threatening conditions, close monitoring and a robust risk-mitigation strategy will be implemented during this study.
Since immunosuppressant effects are a potential risk for inavolisib and bone marrow suppression is very commonly associated with the use of paclitaxel, a possible consequence of immunosuppression may be an increased susceptibility to acute infections including COVID-19. At this time, there is insufficient evidence for a causal association between inavolisib and an increased risk of severe outcomes from COVID-19.
Pneumonitis (lung inflammation) is a potential risk for inavolisib and a few cases of Grade 1, 2 pneumonitis have been observed after treatment with inavolisib. There may be a potential overlap in clinical and radiological features for inavolisib-induced pneumonitis and COVID-19-related interstitial pneumonia.
Available non-clinical and clinical data for inavolisib support the proposed evaluation of inavolisib in combination with paclitaxel in solid tumors in this study. Considering the known safety profiles of inavolisib and paclitaxel and the safety risk mitigation measures incorporated in this study, it is anticipated that the combination treatments in this study will have a manageable safety profile and an acceptable benefit-risk assessment for the conduct of the study.

Where is the study run from?
Genentech, Inc (USA)

When is the study starting and how long is it expected to run for?
July 2020 to July 2024

Who is funding the study?
Genentech, Inc (USA)

Who is the main contact?
global-roche-genentech-trials@gene.com