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

Trial Summary

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.

What data supports the idea that Inavolisib + Atezolizumab for Cancer is an effective drug?

The available research shows that Atezolizumab, when used alone, has shown effectiveness in treating various cancers like bladder cancer and breast cancer. For instance, in advanced bladder cancer, Atezolizumab led to better response rates and survival compared to other treatments, with a 15% response rate in patients who had already tried other treatments. In breast cancer, it has shown promising results in trials, leading to its approval for use. Although specific data on the combination of Inavolisib and Atezolizumab is not provided, the effectiveness of Atezolizumab in these cancers suggests potential benefits when combined with Inavolisib. ^{1 2 3 4 5}

What safety data is available for the cancer treatment Inavolisib + Atezolizumab?

The safety data for Atezolizumab, also known as Tecentriq, has been evaluated in various studies. It is an immune checkpoint inhibitor that blocks PD-L1, enhancing antitumor immune activity. Atezolizumab has been studied in different cancers, including melanoma, triple-negative breast cancer, bladder cancer, and non-small-cell lung cancer. Common immune-related adverse events (irAEs) include hepatitis, colitis, pneumonitis, hypophysitis, hypothyroidism, rash, and musculoskeletal problems. Less common irAEs are acute kidney injury and immune thrombocytopenic purpura. The toxicity profile of Atezolizumab is generally favorable, with ongoing trials assessing its efficacy in various cancer stages. However, specific safety data for the combination of Inavolisib and Atezolizumab is not detailed in the provided research. ^{3 4 5 6 7}

Is the drug Atezolizumab, also known as Tecentriq, a promising treatment for cancer?

Yes, Atezolizumab is a promising drug for cancer treatment. It has shown positive results in treating various cancers like bladder cancer, lung cancer, and breast cancer by boosting the body's immune response against tumors. It has been approved for use in several countries and has demonstrated the ability to improve survival rates and reduce tumor size in some patients. ^{2 4 5 8 9}

What is the purpose of this trial?

The purpose of the study is to assess the safety and efficacy of inavolisib as a single-agent and in combination with atezolizumab in participants with phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA)-mutated cancers, including previously treated head and neck squamous cell carcinoma (HNSCC).

Research Team

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Eligibility Criteria

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 know if my cancer is HPV positive or negative.

I cannot undergo surgery or radiation for my condition.

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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, 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, 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, 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 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, 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, 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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Atezolizumab (MPDL3280A) Monotherapy for Patients With Metastatic Urothelial Cancer: Long-term Outcomes From a Phase 1 Study. [2022]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Atezolizumab: First Global Approval. [2019]

3. England pubmed.ncbi.nlm.nih.gov

Atezolizumab for use in PD-L1-positive unresectable, locally advanced or metastatic triple-negative breast cancer. [2020]

4. England pubmed.ncbi.nlm.nih.gov

The safety of atezolizumab plus chemotherapy for the treatment of metastatic lung cancer. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Atezolizumab: A PD-L1-Blocking Antibody for Bladder Cancer. [2022]

6. United States 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. [2020]

7. England pubmed.ncbi.nlm.nih.gov

Possible atezolizumab-associated acute kidney injury and immune thrombocytopenia. [2022]

8. New Zealand pubmed.ncbi.nlm.nih.gov

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

9. England pubmed.ncbi.nlm.nih.gov

Atezolizumab for the treatment of colorectal cancer: the latest evidence and clinical potential. [2022]