RO7496353 Combination Therapy for Metastatic Cancer

Not currently recruiting at 47 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment, RO7496353 (an experimental treatment), combined with other cancer medicines for individuals with certain advanced or spreading cancers, such as lung, stomach, pancreatic, and bladder cancer. The main goal is to determine the safety and effectiveness of these combinations against these cancers. Individuals with a confirmed diagnosis of one of these cancers who have not received cancer treatment in the last three weeks might be suitable candidates. As a Phase 1 trial, this research aims to understand how the treatment 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 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.

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

Research has shown that the combination of RO7496353 and atezolizumab may help treat various types of cancer, but it is still undergoing safety testing. Atezolizumab, already used in other cancer treatments, is generally considered effective and tolerable. For instance, in patients with advanced bladder cancer, atezolizumab proved effective after other treatments failed, though some patients experienced immune-related side effects. These side effects were serious in about 12% of cases, with only 2% being very severe.

Nivolumab, another drug in this trial, has also demonstrated safety and effectiveness when combined with chemotherapy for stomach cancer. Research indicates it helps patients with advanced stomach cancer live longer, and its safety is deemed acceptable.

This study is in its early stages and primarily focuses on safety. Researchers are still gathering information to understand how well patients tolerate RO7496353 when used with these drugs. Participants in this trial will provide crucial information on the safety and effectiveness of this new treatment combination. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for metastatic cancer, like chemotherapy and traditional immunotherapies, RO7496353 is a novel component of a combination therapy aimed at enhancing the immune response against tumors. Researchers are excited about this because RO7496353 is designed to work alongside checkpoint inhibitors like atezolizumab and nivolumab, potentially boosting their effectiveness. Additionally, in certain arms like Cohort B, the combination includes oxaliplatin and either capecitabine or S-1, which might provide a more comprehensive approach to tackling different types of metastatic cancer. This multifaceted strategy could offer a more robust and targeted attack on cancer cells, possibly leading to better outcomes for patients.

What evidence suggests that this trial's treatments could be effective for metastatic cancer?

In this trial, participants with urothelial carcinoma (UC) will receive a combination of RO7496353 and atezolizumab. Previous studies have shown that atezolizumab helped patients with UC live longer, with tumors shrinking in 14.3% of these patients. For non-small cell lung cancer (NSCLC), participants will also receive RO7496353 and atezolizumab, as studies have shown that using atezolizumab with chemotherapy led to 63.7% of patients surviving for at least a year. In gastric cancer (GC), participants will receive RO7496353, nivolumab, and chemotherapy, as previous research indicates that nivolumab combined with chemotherapy caused tumors to shrink in 55.6% of patients. For pancreatic ductal adenocarcinoma (PDAC), participants will receive RO7496353 and atezolizumab, although past studies have not found combining atezolizumab with other drugs to be very effective. These findings suggest that while potential benefits exist, treatment effectiveness can vary for different cancer types. ^{1 2 4 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 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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

Group I: Substudy: UC Experimental Treatment 2 Interventions

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

Group II: 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 PD.

Group III: 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 PD.

Group IV: 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 (PD).

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

Industry Sponsor

Trials

105

Recruited

25,000+

Dr. Osamu Okuda

Chugai Pharmaceutical

Chief Executive Officer since 2020

MD from Kyoto University

Dr. Mariko Y. Momoi

Chugai Pharmaceutical

Chief Medical Officer

MD from Jichi Medical University

Chugai Pharmaceutical Co.

Collaborator

Trials

4

Recruited

380+

Published Research Related to This Trial

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, 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, 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 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]

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]

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]

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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11696331/

Outcomes of Combined Atezolizumab Plus Chemotherapy in ... The objectives of this study were to confirm the treatment outcomes of combined atezolizumab plus chemotherapy, and to identify prognostic factors.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05867121

NCT05867121 | A Study to Evaluate Safety, ... The purpose of this study is to evaluate the safety and tolerability of RO7496353 in combination with a checkpoint inhibitor (CPI) with or without standard-of- ...

3. cancernetwork.com cancernetwork.com/view/atezolizumab-combo-real-world-data-match-clinical-trial-efficacy-in-sclc

Atezolizumab Combo Real-World Data Match Clinical Trial ... In the overall efficacy population, the median overall survival (OS) was 16.5 months (95% CI, 14.9-18.2), and the 12-month OS rate was 63.7% (95 ...

4. researchgate.net researchgate.net/publication/387756589_Outcomes_of_Combined_Atezolizumab_Plus_Chemotherapy_in_Non-small_Cell_Lung_Cancer_Patients_in_Clinical_Practice

Outcomes of Combined Atezolizumab Plus Chemotherapy ... Immune-related adverse events were observed in 27.7% of patients, with grade 3 or higher in 9.9% of patients, and grade 5 in 2.1% of patients.

5. synapse.patsnap.com synapse.patsnap.com/drug/4a26e2b0788548f78fe55720d5122930

RO-7496353 - Drug Targets, Indications, Patents A Phase Ib, Open-label, Multicenter Dose-expansion Study Evaluating the Safety, Pharmacokinetics, and Activity of RO7496353 in Combination With a Checkpoint ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39758245/

Outcomes of Combined Atezolizumab Plus Chemotherapy ... Immune-related adverse events were observed in 27.7% of patients, with grade 3 or higher in 9.9% of patients, and grade 5 in 2.1% of patients.

7. australianclinicaltrials.gov.au australianclinicaltrials.gov.au/anzctr-search-results?search_text=&condition_category=all&purpose_of_study=all&recruitment_status=all&recruitment_sites=NSW&phase=all&gender=all&healthy_volunteers=all&ethics_approval=Yes&condition_code=all&page=677

ANZCTR search results | Australian Clinical ... The purpose of this study is to evaluate the safety and tolerability of RO7496353 in combination with a checkpoint inhibitor (CPI) with or without ...