Inavolisib for Solid Cancers and Breast Cancer

Not currently recruiting at 15 trial locations

Overseen By Reference Study ID Number: GO39374 https://forpatients.roche.com/

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Genentech, Inc.

Must be taking: Endocrine therapies

Must not be taking: Anti-hyperglycemics, PI3K inhibitors

Disqualifiers: Diabetes, CNS metastases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called inavolisib for individuals with certain advanced cancers, such as breast cancer, that have a specific genetic change known as the PIK3CA mutation. The researchers aim to assess the safety and tolerability of inavolisib when used alone or with other cancer treatments. Participants will join different groups to test various combinations of inavolisib with other medications. The trial seeks individuals with advanced PIK3CA-mutant cancers, like breast cancer, who can provide a tumor sample for testing. As a Phase 1 trial, this research focuses on understanding how inavolisib works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you have diabetes requiring medication or certain heart conditions, you may not be eligible to participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that inavolisib, when used alone, is generally safe. In one study, patients tolerated it well, with no new or unexpected side effects. Combining inavolisib with letrozole also appears promising. Studies have found it to be safe, with no new safety concerns.

For those considering inavolisib with fulvestrant, this combination has been reported as safe and manageable. Patients generally tolerated it and experienced some tumor reduction. In another combination with palbociclib and fulvestrant, patients showed significant improvement, and it was considered safe.

Inavolisib combined with palbociclib, fulvestrant, and metformin is still under safety evaluation, but no unexpected issues have emerged so far. Lastly, when inavolisib is combined with trastuzumab and pertuzumab, long-term safety data suggests it is well-tolerated with no surprising side effects.

These findings are encouraging, but always consult a healthcare provider before considering joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for solid and breast cancers, which often involve chemotherapy or hormone therapy, Inavolisib stands out due to its targeted action on the PI3K pathway, a key player in cancer cell growth and survival. Researchers are excited about Inavolisib because it offers the potential to directly inhibit cancer cell proliferation with potentially fewer side effects than traditional treatments. Additionally, its combination with other agents like letrozole, fulvestrant, palbociclib, and metformin in different trial arms is designed to enhance effectiveness and tackle cancer cells from multiple angles, paving the way for more personalized and effective treatment strategies.

What evidence suggests that this trial's treatments could be effective for solid cancers and breast cancer?

Research shows that inavolisib, a drug targeting the protein PI3Kα, holds promise for treating solid cancers like breast cancer. In this trial, participants may receive inavolisib alone or with other drugs such as letrozole, fulvestrant, or palbociclib, depending on the treatment arm. Studies have found that inavolisib treatments can significantly extend the time patients live without cancer worsening. Specifically, one study discovered that inavolisib treatment more than doubled the response rate and nearly doubled the time patients lived without cancer progression compared to standard treatments. This suggests that inavolisib could be a good option for patients with certain genetic changes in their cancer. ^{6 7 8 9 10}

Who Is on the Research Team?

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Are You a Good Fit for This Trial?

This trial is for adults with advanced or metastatic solid tumors, including breast cancer, that have a specific mutation (PIK3CA). Participants must be in good physical condition (ECOG 0 or 1) and expected to live at least 12 weeks. Women with hormone receptor-positive/HER2-negative or HER2-positive breast cancer are eligible. Key exclusions include recent other cancers, significant heart conditions, uncontrolled illnesses, prior treatments with certain drugs, and inability to swallow pills.

Inclusion Criteria

You are expected to live for at least 12 weeks.

I am a woman with advanced breast cancer that is HER2 positive and has a PIK3CA mutation.

I can provide a tissue sample from my cancer for testing.

Exclusion Criteria

I have untreated brain metastases.

I have previously been treated with a CDK4/6 inhibitor.

I have a long QT syndrome or a family history of sudden death related to it.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose-Escalation Stage (Stage I)

Participants receive inavolisib as a single agent or in combination with other therapies to determine the optimal dose

28-35 days per cycle

Multiple visits per cycle

Expansion Stage (Stage II)

Participants receive inavolisib in combination with other therapies based on results from Stage I

28 days per cycle

Multiple visits per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Fulvestrant
• Inavolisib
• Letrozole
• Metformin
• Palbociclib
• Pertuzumab
• Trastuzumab

Trial Overview The study tests the drug Inavolisib alone or combined with standard therapies for advanced breast cancer. It's an open-label Phase I trial with two stages: dose-escalation to find safe amounts of Inavolisib and expansion to see how well it works across seven different treatment combinations involving drugs like Palbociclib, Letrozole, Fulvestrant, Metformin, Trastuzumab and Pertuzumab.

How Is the Trial Designed?

Group I: Stage II Arm G: Inavolisib + Trastuzumab + Pertuzumab Experimental Treatment 3 Interventions

Participants will receive inavolisib in combination with trastuzumab and pertuzumab (Days 1-21). Dose of inavolisib will be determined from the results of Stage I Arm A. Participants will continue treatment until the end of the study in the absence of unacceptable toxicities and unequivocal disease progression.

Group II: Stage II Arm F: Inavolisib + Palbociclib + Fulvestrant + Metformin Experimental Treatment 4 Interventions

Participants will receive inavolisib (Days 1-28) in combination with palbociclib (Days 1-21), fulvestrant (Days 1 and 15 of Cycle 1; Day 1 for subsequent cycles) and metformin (Days 1-28)(Cycle = 28 days). Dose of inavolisib will be determined from the results of Stage I Arm B. Participants will continue treatment until the end of the study in the absence of unacceptable toxicities and unequivocal disease progression.

Group III: Stage II Arm E: Inavolisib + Palbociclib + Fulvestrant Experimental Treatment 3 Interventions

Participants will receive inavolisib (Days 1-28) in combination with palbociclib (Days 1-21) and fulvestrant (Days 1 and 15 of Cycle 1; Day 1 for subsequent cycles)(Cycle = 28 days). Dose of inavolisib will be determined from the results of Stage I Arm B. Participants will continue treatment until the end of the study in the absence of unacceptable toxicities and unequivocal disease progression.

Group IV: Stage II Arm D: Inavolisib + Fulvestrant Experimental Treatment 2 Interventions

Participants will receive inavolisib on Days 1-28 in combination with fulvestrant on Day 1 and 15 of Cycle 1 and then on Day 1 from Cycle 2 (cycle length: 28 days). Dose of inavolisib will be decided based on the results of Stage I Arm C. Participants will continue treatment until the end of the study in the absence of unacceptable toxicities and unequivocal disease progression.

Group V: Stage II Arm C: Inavolisib + Letrozole Experimental Treatment 2 Interventions

Participants will receive inavolisib in combination with letrozole on Days 1-28 of each 28-day cycle. Dose of inavolisib will be decided based on the results of Stage I Arm C. Participants will continue treatment until the end of the study in the absence of unacceptable toxicities and unequivocal disease progression.

Group VI: Stage II Arm B: Inavolisib + Palbociclib + Letrozole Experimental Treatment 3 Interventions

Participants will receive inavolisib on Days 1-28 in combination with palbociclib on Days 1-21 and letrozole on Days 1-28 of each 28-day cycle. Dose of inavolisib will be decided based on the results of Stage I Arm B. Participants will continue treatment until the end of the study in the absence of unacceptable toxicities and unequivocal disease progression.

Group VII: Stage I Arm C: Inavolisib + Letrozole Experimental Treatment 2 Interventions

Participants will receive inavolisib in escalating dose levels along with letrozole on Days 1-28 of each 28-day cycle. The starting dose of inavolisib will not exceed the starting dose in Stage I Arm A. Participants will continue treatment until the end of the study in the absence of unacceptable toxicities and unequivocal disease progression.

Group VIII: Stage I Arm B: Inavolisib + Palbociclib + Letrozole Experimental Treatment 3 Interventions

Participants will receive inavolisib in escalating dose levels (starting dose 3 mg) on Days 1-28, palbociclib on Days 1-21, and letrozole on Days 1-28 of each 28-day cycle. Participants will continue treatment until the end of the study in the absence of unacceptable toxicities and unequivocal disease progression.

Group IX: Stage I Arm A: Inavolisib Single Agent Experimental Treatment 1 Intervention

Participants will receive inavolisib in escalating dose levels with starting dose of 6 milligrams (mg). Participants will receive single dose of inavolisib on Day 1 of Cycle 1 followed by once daily from Day 8 of Cycle 1. (Cycle length: 35 days for Cycle 1 and 28 days for all other cycles). Participants will continue treatment until the end of the study in the absence of unacceptable toxicities and unequivocal disease progression.

Inavolisib is already approved in United States for the following indications:

Approved in United States as Itovebi for:

• Locally advanced or metastatic hormone receptor-positive, HER2-negative breast cancer with PIK3CA mutations, following recurrence on or after completing adjuvant endocrine therapy

Who Is Running the Clinical Trial?

Genentech, Inc.

Lead Sponsor

Trials

1,578

Recruited

569,000+

Ashley Magargee

Genentech, Inc.

Chief Executive Officer since 2024

MBA from Harvard University, BA from Princeton University

Levi Garraway

Genentech, Inc.

Chief Medical Officer since 2021

MD, PhD

Citations

1. aacrjournals.org aacrjournals.org/cancerres/article/82/4_Supplement/P5-17-05/681415/Abstract-P5-17-05-A-phase-I-Ib-study-of-inavolisib

Abstract P5-17-05: A phase I/Ib study of inavolisib (GDC-0077 ... Inavolisib is a PI3Kα-selective inhibitor and degrader of mutated PI3Kα that has demonstrated encouraging preliminary antitumor activity in patients with PIK3 ...

2. itovebi-hcp.com itovebi-hcp.com/efficacy/clinical-results.html

INAVO120 Clinical Trial Results | Itovebi™ (inavolisib) Itovebi regimen more than doubled ORR and nearly doubled mDOR vs placebo + palbociclib and fulvestrant (secondary endpoints)1,2. OBJECTIVE RESPONSE RATE (ORR)1* ...

3. nejm.org nejm.org/doi/10.1056/NEJMoa2404625

Inavolisib-Based Therapy in PIK3CA-Mutated Advanced ... Inavolisib plus palbociclib–fulvestrant led to significantly longer progression-free survival than placebo plus palbociclib–fulvestrant, with a greater ...

4. cuba.dialogoroche.com cuba.dialogoroche.com/content/dam/roche-dialogo/global-assets/downloadable-assets/congresos-y-eventos/oncology/sabcs-2021/posters/5_poster_juric_a_phase_I_Ib_study_of_inavolisib_in_combination_with_fulvestrant_in_patients_with_pik3ca_mutated_hormone_sabcs_2021.pdf

A phase I/Ib study of inavolisib (GDC-0077) in combination ... Inavolisib continues to be developed in breast cancer and other solid tumors. • A phase III, randomized, double-blind, placebo-controlled study assessing the ...

5. roche.com roche.com/media/releases/med-cor-2025-05-31

New data show Roche's Itovebi significantly extended ... These data showed Itovebi TM (inavolisib), in combination with palbociclib (Ibrance®) and fulvestrant, reduced the risk of death by more than 30% compared with ...

6. esmoopen.com esmoopen.com/article/S2059-7029(25)01172-X/pdf

Safety overview and management of inavolisib alone and ... Inavolisib was evaluated in a first-in-human, open-label, multicenter, phase I/Ib dose-escalation and dose-expansion study (GO39374; NCT03006172) ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT03006172

Study Details | NCT03006172 | To Evaluate the Safety, ... This is an open-label, multicenter, Phase I study designed to evaluate the safety, tolerability, and pharmacokinetics of inavolisib administered orally as a ...

8. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2024/219249s000lbl.pdf

Itovebi (Inavolisib) Tablets, for Oral Use - accessdata.fda.gov The safety of ITOVEBI was evaluated in a randomized, double-blind, placebo-controlled study (INAVO120) in. 324 patients with PIK3CA-mutated, HR-positive, HER2- ...

9. genentech-clinicaltrials.com genentech-clinicaltrials.com/en/trials/cancer/bc/to-evaluate-the-safety--tolerability--and-pharmacokinetics-of-gd.html

Clinical Trial – Breast Cancer, Solid Tumor – Safety, Tol... This is an open-label, multicenter, Phase I study designed to evaluate the safety, tolerability, and pharmacokinetics of inavolisib administered orally as a ...

10. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.1062

Phase Ib study of inavolisib (INAVO) + weekly paclitaxel ... INAVO + wP was well tolerated in pts with LA/m solid tumors, including those with a PIK3CA mutation, with no new safety signals or drug–drug interactions ...