RO7496353 Combination Therapy for Metastatic Cancer

Recruiting at 35 trial locations

Overseen By Reference Study ID Number: GO44010 https://forpatients.roche.com/

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Genentech, Inc.

Must not be taking: Chemotherapy, Hormonal therapy

Disqualifiers: Pregnancy, CNS metastases, Cardiovascular disease, HIV, Hepatitis, 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: Unknown

Duration: 21-day or 28-day cycles, up to approximately 29 months

102 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you stop any anti-cancer therapy, including chemotherapy, hormonal therapy, and radiotherapy, at least 3 weeks before starting the study treatment. The protocol does not specify about other medications, so it's best to discuss your current medications with the study team.

What data supports the effectiveness of the drug combination therapy RO7496353 for metastatic cancer?

Atezolizumab, one of the drugs in the combination, has shown effectiveness in treating various cancers like urothelial carcinoma, non-small cell lung cancer, and triple-negative breast cancer. Nivolumab, another drug in the combination, has been effective in treating cancers such as melanoma, non-small cell lung cancer, and renal cell cancer. These drugs work by helping the immune system better recognize and attack cancer cells. ^{1 2 3 4 5}

Is atezolizumab generally safe for humans?

Atezolizumab, used in various cancers, has a favorable safety profile but can cause immune-related side effects like hepatitis (liver inflammation), colitis (colon inflammation), and pneumonitis (lung inflammation). Rarely, it may lead to acute kidney injury and immune thrombocytopenia (low platelet count). ^{2 3 6 7 8}

What makes the drug combination of Atezolizumab, Nivolumab, and RO7496353 unique for treating metastatic cancer?

This drug combination is unique because it includes Atezolizumab, a monoclonal antibody that targets PD-L1 to enhance the immune system's ability to fight cancer, and is used in combination with other immune checkpoint inhibitors like Nivolumab, potentially offering a novel approach to boost antitumor activity in metastatic cancer. ^{1 2 9 10 11}

What is the purpose of this trial?

The purpose of this study is to evaluate the safety and tolerability of RO7496353 when administered in combination with a checkpoint inhibitor (CPI) with or without standard-of-care (SOC) chemotherapy in participants with locally advanced or metastatic solid tumors such as non-small cell lung cancer (NSCLC), gastric cancer (GC) and pancreatic ductal adenocarcinoma (PDAC). The study will be conducted in 2 stages: an initial safety run-in stage and an expansion stage.

Research Team

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Eligibility Criteria

This trial is for adults with certain advanced cancers (like stomach, pancreatic, or non-small cell lung cancer) who are in fairly good health and have a life expectancy of at least 3 months. They must have measurable disease on scans and be able to provide tumor samples. People with poor performance status or inadequate organ function cannot join.

Inclusion Criteria

You are expected to live for at least 3 more months.

My cancer is advanced, has come back, or spread and cannot be cured.

I am fully active or restricted in physically strenuous activity but can do light work.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Safety Run-in

Initial safety evaluation of RO7496353 in combination with a checkpoint inhibitor with or without standard-of-care chemotherapy

Varies by cohort

Treatment

Participants receive RO7496353 in combination with a checkpoint inhibitor and possibly chemotherapy, administered in cycles until unacceptable toxicity or disease progression

21-day or 28-day cycles, up to approximately 29 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Atezolizumab
• Nivolumab
• RO7496353

Trial Overview The study tests RO7496353 combined with checkpoint inhibitors (like Atezolizumab or Nivolumab) and may include standard chemotherapy drugs (Gemcitabine, Oxaliplatin, etc.). It's done in two parts: first checking safety and then seeing how well it works.

Participant Groups

Group I: Cohort C: PDAC Experimental Treatment 4 Interventions

Participants with PDAC will receive RO7496353, and atezolizumab, given as an IV infusion at an assigned dose on Days 1 and 15 of each 28-day cycle along with nab-paclitaxel, and gemcitabine, also given as an IV infusion on Days 1, 8, 15 of each 28-day cycle until unacceptable toxicity or symptomatic deterioration attributed to disease progression.

Group II: Cohort B: GC Experimental Treatment 5 Interventions

Participants with GC will receive RO7496353, nivolumab, and oxaliplatin, given as an IV infusion at an assigned dose on Day 1 of each 21-day cycle along with either capecitabine or S-1, orally, twice daily on Days 1 to 14 of each cycle until unacceptable toxicity or symptomatic deterioration attributed to disease progression.

Group III: Cohort A: NSCLC Experimental Treatment 2 Interventions

Participants with NSCLC will receive RO7496353, and atezolizumab, given as an intravenous (IV) infusion at an assigned dose on Day 1 of each 21-day cycle until unacceptable toxicity or symptomatic deterioration attributed to disease progression.

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?

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

Chugai Pharmaceutical Co.

Collaborator

Trials

4

Recruited

380+

Findings from Research

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, 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]

Nivolumab and pembrolizumab are FDA-approved monoclonal antibodies that target PD-1, helping to enhance T cell activity against cancer by blocking the PD-1/PD-L1 interaction, which allows cancer cells to escape immune detection.

Both drugs have shown efficacy across multiple cancer types, including melanoma and non-small cell lung cancer, and are considered interchangeable options for treating these conditions, which may help manage the rising costs of cancer therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab and pembrolizumab: Monoclonal antibodies against programmed cell death-1 (PD-1) that are interchangeable. Prasad, V., Kaestner, V.[2022]

Nivolumab plus ipilimumab showed durable and long-term efficacy in treating advanced non-small cell lung cancer (NSCLC) compared to chemotherapy, regardless of tumor PD-L1 expression levels.

These findings are based on updated results from part 1 of the phase 3 CheckMate 227 trial, indicating that this combination therapy could be a more effective frontline treatment option for NSCLC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab/Ipilimumab Combo Yields Durable Efficacy in Advanced NSCLC. Kahl, KL.[2021]

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, 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]

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 chemotherapy (ABCP or ACnP) has been shown to significantly improve progression-free survival (PFS) and overall survival (OS) in chemotherapy-naïve patients with metastatic nonsquamous non-small cell lung cancer (NSCLC), based on the IMpower150 and IMpower130 studies.

Both treatment regimens (ABCP and ACnP) demonstrated manageable safety profiles, with most immune-related side effects being mild to moderate and reversible, making them promising first-line options for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab First-Line Combination Therapy: A Review in Metastatic Nonsquamous NSCLC. Dhillon, S., Syed, YY.[2020]

The phase III IMmotion151 trial demonstrated that the combination of atezolizumab and bevacizumab significantly improves progression-free survival in patients with advanced or metastatic renal cell carcinoma compared to sunitinib.

Patients with PD-L1-positive tumors experienced an even greater benefit, with an increase in progression-free survival of 3.5 months, highlighting the efficacy of this combination therapy in specific patient populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug Combo Bests Sunitinib in RCC. [2019]

References

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

Atezolizumab: First Global Approval. [2019]

2. England pubmed.ncbi.nlm.nih.gov

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

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

Nivolumab and pembrolizumab: Monoclonal antibodies against programmed cell death-1 (PD-1) that are interchangeable. [2022]

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

Nivolumab/Ipilimumab Combo Yields Durable Efficacy in Advanced NSCLC. [2021]

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

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

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

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

8. England pubmed.ncbi.nlm.nih.gov

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

9. Ireland pubmed.ncbi.nlm.nih.gov

Atezolizumab in patients with advanced non-small cell lung cancer and history of asymptomatic, treated brain metastases: Exploratory analyses of the phase III OAK study. [2019]

10. France pubmed.ncbi.nlm.nih.gov

Atezolizumab First-Line Combination Therapy: A Review in Metastatic Nonsquamous NSCLC. [2020]

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

Drug Combo Bests Sunitinib in RCC. [2019]