Inavolisib + Atezolizumab for Cancer

Recruiting at 5 trial locations

Overseen By Reference Study ID Number: CO43909 https://forpatients.roche.com/

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Hoffmann-La Roche

Must not be taking: CYP3A4 inducers, CYP3A4 inhibitors

Disqualifiers: Diabetes, CNS metastases, HIV, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 1

Duration: 6-12 weeks

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial evaluates the safety and effectiveness of two drugs, inavolisib and atezolizumab, for people with certain types of cancer. It targets cancers with a specific mutation called PIK3CA, such as head and neck cancer that has returned or spread after treatment. Participants will take either inavolisib (also known as Itovebi or GDC-0077) alone or in combination with atezolizumab (also known as Tecentriq). This trial may suit individuals with PIK3CA-mutated head and neck cancer that cannot be treated with surgery or radiation.

As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive this new treatment.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you are on certain medications like strong CYP3A4 inducers or inhibitors, or if you have been treated with chemotherapy, radiotherapy, or other anti-cancer therapies within 2 weeks before enrollment. It's best to discuss your current medications with the trial team.

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

Research shows that inavolisib is generally safe when used alone, and patients have tolerated it well over time. Studies have demonstrated that inavolisib effectively controls cancers with PIK3CA mutations.

When combined with atezolizumab, safety remains a key focus. The FDA has already approved atezolizumab for other uses, indicating its general safety. Current research examines how these two drugs work together in cancers with PIK3CA mutations. Although this research is still in the early stages, existing data on each drug is promising for their combined use. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Inavolisib and Atezolizumab for cancer treatment because it brings a novel approach to tackling the disease. Inavolisib is a PI3K inhibitor, which targets a specific pathway often involved in cancer cell growth, offering a new mechanism of action compared to traditional treatments like chemotherapy or hormone therapy. Meanwhile, Atezolizumab is an immunotherapy drug that helps the immune system recognize and attack cancer cells, providing a different angle from standard therapies. Together, they could potentially enhance effectiveness by attacking cancer on multiple fronts, making this combination a promising advance over existing treatments.

What evidence suggests that this trial's treatments could be effective for PIK3CA-mutated cancers?

Research has shown that inavolisib offers promising results for treating cancers with PIK3CA mutations. It has been linked to slowing disease progression and extending survival in certain cancer types. Early studies found that 60% of patients with PIK3CA-mutated tumors had their disease under control at week 8, and 32% at week 16. In this trial, one group of participants will receive inavolisib alone, while another group will receive a combination of inavolisib and atezolizumab. Studies indicate that combining inavolisib with atezolizumab significantly aids in controlling cancer growth over time. These findings suggest that this combination could be effective against PIK3CA-mutated cancers, including those in the head and neck. ^{1 2 3 6 7}

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 people with PIK3CA-mutated cancers, specifically those who have previously treated head and neck squamous cell carcinoma (HNSCC). Participants must not be suitable for surgery/radiation, have a life expectancy of at least 12 weeks, an ECOG Performance Status of 0 or 1, and provide tissue samples. Exclusions include prior treatment with certain inhibitors, diabetes requiring systemic treatment, recent malignancies other than HNSCC within the last five years, cardiovascular issues, allergies to inavolisib components among others.

Inclusion Criteria

I cannot undergo surgery or radiation for my condition.

I know if my cancer is HPV positive or negative.

My tumor has a PIK3CA mutation.

Exclusion Criteria

I have previously been treated with a PI3K, AKT, or mTOR inhibitor.

I have diabetes and am on medication.

I have not had any other cancer in the last 5 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive inavolisib tablets daily and atezolizumab infusions every 3 weeks

6-12 weeks

1 visit every 3 weeks for IV infusion

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Atezolizumab
• Inavolisib

Trial Overview The study tests the safety and effectiveness of Inavolisib alone and combined with Atezolizumab in treating cancer. It targets patients whose tumors show a specific genetic change (PIK3CA mutation) and measures how well these treatments work against their cancer.

How Is the Trial Designed?

Group I: Arm B Experimental Treatment 2 Interventions

Participants in this group will receive inavolisib tablets, to be taken PO, QD and atezolizumab given as an intravenous (IV) infusion once every 3 weeks (Q3W).

Group II: Arm A Experimental Treatment 1 Intervention

Participants in this group will receive inavolisib tablets, to be taken by mouth (PO), once daily (QD), on Days 1-21 of each cycle.

Atezolizumab is already approved in United States, European Union for the following indications:

Approved in United States as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

Approved in European Union as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

Who Is Running the Clinical Trial?

Hoffmann-La Roche

Lead Sponsor

Trials

2,482

Recruited

1,107,000+

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Avastin, Herceptin, Rituxan, Accu-Chek

Dr. Levi Garraway

Hoffmann-La Roche

Chief Medical Officer since 2019

MD from the University of Basel

Dr. Thomas Schinecker

Hoffmann-La Roche

Chief Executive Officer since 2023

PhD in Molecular Biology from New York University

Published Research Related to This Trial

Atezolizumab, combined with nab-paclitaxel, significantly improved progression-free survival in patients with advanced triple-negative breast cancer (TNBC) compared to placebo, based on the phase III IMpassion130 trial involving patients with unresectable locally advanced or metastatic TNBC.

While the combination therapy showed a tolerable safety profile, with common side effects like neutropenia and immune-related adverse events, it did not significantly affect health-related quality of life for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab (in Combination with Nab-Paclitaxel): A Review in Advanced Triple-Negative Breast Cancer. Kang, C., Syed, YY.[2020]

Atezolizumab, an anti-PD-L1 therapy, was well tolerated in a study of 45 patients with advanced melanoma, showing that most side effects were mild (grade 1/2) and no treatment-related deaths occurred.

The treatment resulted in a 30% overall response rate and a median overall survival of 23 months, with certain biomarkers like PD-L1 expression and tumor mutational burden linked to better outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, Clinical Activity, and Biological Correlates of Response in Patients with Metastatic Melanoma: Results from a Phase I Trial of Atezolizumab. Hamid, O., Molinero, L., Bolen, CR., et al.[2020]

Atezolizumab, an anti-PD-L1 therapy, showed long-term safety and efficacy in patients with metastatic urothelial carcinoma, with a median follow-up of 37.8 months and a low incidence of severe treatment-related adverse events (9%).

The treatment resulted in a 26% objective response rate, with a median duration of response of 22.1 months, and median overall survival of 10.1 months, particularly benefiting patients with higher PD-L1 expression on immune cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab (MPDL3280A) Monotherapy for Patients With Metastatic Urothelial Cancer: Long-term Outcomes From a Phase 1 Study. Petrylak, DP., Powles, T., Bellmunt, J., et al.[2022]

Atezolizumab is a monoclonal antibody that targets PD-L1, which is being developed for treating various blood cancers and solid tumors, showing promise in cancer immunotherapy.

It has already been approved in the US as a second-line treatment for urothelial carcinoma and is pending approval for non-small cell lung cancer, highlighting its potential efficacy in these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab: First Global Approval. Markham, A.[2019]

Atezolizumab, a monoclonal antibody targeting PD-L1, has shown significant improvements in progression-free and overall survival in patients with advanced non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC) when combined with chemotherapy, as demonstrated in the IMpower studies.

The safety profile of atezolizumab in combination with chemotherapy is acceptable, with common immune-related adverse events including rash (18-28%), hypothyroidism (8-15%), and hepatitis (5-17%), consistent with its known effects as a single agent, indicating no new safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety of atezolizumab plus chemotherapy for the treatment of metastatic lung cancer. Manzo, A., Carillio, G., Montanino, A., et al.[2022]

Atezolizumab is an FDA-approved treatment for advanced bladder cancer that works by blocking the PD-L1/PD-1 immune checkpoint, enhancing T-cell immunity against tumors.

In clinical trials, atezolizumab showed a 15% objective response rate in patients whose cancer progressed after chemotherapy, and a 24% response rate in chemotherapy-naïve patients, with a favorable safety profile compared to other second-line treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab: A PD-L1-Blocking Antibody for Bladder Cancer. Inman, BA., Longo, TA., Ramalingam, S., et al.[2022]

Atezolizumab, the first anti-PD-L1 monoclonal antibody approved by the FDA, has shown promising efficacy in treating metastatic triple-negative breast cancer, supported by data from the Phase III IMpassion130 trial.

The review highlights the pharmacodynamic and pharmacokinetic properties of atezolizumab, emphasizing its safety and effectiveness in various cancers, including small-cell lung cancer and renal cell cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab for use in PD-L1-positive unresectable, locally advanced or metastatic triple-negative breast cancer. Mavratzas, A., Seitz, J., Smetanay, K., et al.[2020]

Atezolizumab, an immune checkpoint inhibitor used for treating non-small cell lung cancer, can cause rare but serious immune-related adverse events (irAEs) such as acute kidney injury (AKI) and immune thrombocytopenic purpura (ITP).

In a case study of a patient receiving atezolizumab, the development of AKI and ITP occurred one week after treatment initiation, but with appropriate management including IVIG and steroids, the patient's condition improved and was discharged for routine follow-up.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Possible atezolizumab-associated acute kidney injury and immune thrombocytopenia. Yılmaz, A., Mirili, C., Bilici, M., et al.[2022]

Atezolizumab, a monoclonal antibody targeting PD-L1, shows promising efficacy in treating metastatic colorectal cancer (mCRC), particularly in patients with deficient mismatch repair (dMMR), indicating a potential new treatment avenue for this subgroup.

Ongoing clinical trials suggest that atezolizumab may be even more effective when combined with chemotherapy or targeted therapies, such as the MEK inhibitor cobimetinib, paving the way for its inclusion in future treatment protocols for mCRC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab for the treatment of colorectal cancer: the latest evidence and clinical potential. Tapia Rico, G., Price, TJ.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9762331/

RTK-Dependent Inducible Degradation of Mutant PI3Kα ... Indeed, combination of the HER2 inhibitor lapatinib with GDC-0077 in vitro results in increased efficacy in six of seven HER2-amplified breast cancer cell lines ...

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

New data show Roche's Itovebi significantly extended ... The ItovebiTM (inavolisib)-based regimen reduced the risk of death by more than 30% in people with PIK3CA-mutated HR-positive, HER2-negative ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.1052

Long-term safety of inavolisib (GDC-0077) in an ongoing ... Inavolisib is a PI3Kα-specific inhibitor that also promotes degradation of mutant p110α. It has demonstrated encouraging preliminary antitumor activity.

4. aacrjournals.org aacrjournals.org/cancerdiscovery/article-pdf/doi/10.1158/2159-8290.CD-21-0072/3022822/2159-8290_cd-21-0072v1.pdf

Inducible degradation of mut PI3Kα drives GDC-0077 efficacy the HER2 inhibitor lapatinib with GDC-0077 in vitro results in increased efficacy in 6 out of 7. 313. HER2-amplified breast cancer cell lines (average excess ...

5. ascopost.com ascopost.com/issues/june-10-2025/overall-survival-benefit-achieved-with-inavolisib-plus-palbociclib-and-fulvestrant-in-advanced-breast-cancer/

Overall Survival Benefit Achieved With Inavolisib Plus ... Key Results and Tolerability · Median overall survival: 34.0 vs 27.0 months (HR = 0.67; P = . · Overall survival probability: 87.0% vs 76.7% at 12 ...

6. itovebi-hcp.com itovebi-hcp.com/side-effects/summary.html

Itovebi Regimen Safety Profile See safety data from the INAVO120 clinical trial of Itovebi™ (inavolisib). Visit our website. See full safety for more information.

7. onclive.com onclive.com/view/inavolisib-demonstrates-safety-disease-control-in-pik3ca-mutated-solid-tumors

Inavolisib Demonstrates Safety, Disease Control in PIK3CA ... Inavolisib demonstrated a favorable safety profile and generated disease control in patients with tumors harboring PIK3CA mutations.