RO7502175 + Atezolizumab for Advanced Cancers

Recruiting at 54 trial locations

Overseen By Reference Study ID Number: GO43860 https://forpatients.roche.com/

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Genentech, Inc.

Must not be taking: Chemotherapy, Hormonal therapy

Disqualifiers: HIV, Hepatitis B/C, Autoimmune, 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: 4

450 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the safety and effectiveness of a new drug, RO7502175, both alone and in combination with atezolizumab (Tecentriq) or pembrolizumab, for individuals with advanced solid tumors. It targets cancers such as non-small-cell lung cancer, melanoma, and breast cancer, among others. Participants will assist researchers in determining the optimal dose and monitoring tumor response. This trial suits those with confirmed advanced cancers that have not responded to other treatments. As a Phase 1 trial, the research focuses on understanding 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, or radiotherapy, at least 3 weeks before starting the study treatment.

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

A previous study found atezolizumab effective in treating advanced bladder cancer and non-small cell lung cancer. It extended some patients' lives and was generally well-tolerated. Common side effects included tiredness and nausea, typical of cancer treatments.

For RO7502175, this is the first human study to assess its safety and efficacy. As research is in its early stages, detailed safety information is not yet available. However, the trial is closely monitored to ensure safety.

Prospective participants should know that while atezolizumab has been safe in other conditions, RO7502175 is new and still under investigation. Always consult your doctor about potential risks and benefits. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about RO7502175 in combination with atezolizumab because it offers a fresh approach to battling advanced cancers. While most current treatments for solid tumors focus on standard chemotherapy or established immunotherapies, RO7502175 is designed to enhance the immune response by targeting new pathways. When combined with atezolizumab, an existing immunotherapy that blocks the PD-L1 protein, this duo could potentially offer a more powerful immune attack against tumors. This novel combination aims to improve effectiveness and overcome resistance seen with existing therapies.

What evidence suggests that this trial's treatments could be effective for advanced cancers?

Research shows that RO7502175, a treatment in this trial, targets and removes certain immune cells (called CCR8+ Treg cells) found in tumors. This process is believed to help the body's immune system fight cancer cells more effectively. Early lab studies have shown that RO7502175 can successfully eliminate these cells, suggesting it might improve the immune system's ability to combat cancer.

Atezolizumab, another treatment option in this trial, has proven effective in treating some advanced cancers, such as bladder and non-small cell lung cancer. It works by blocking a protein that prevents the immune system from attacking cancer cells, potentially improving survival rates. The combination of RO7502175 with atezolizumab, tested in this trial, aims to further enhance the immune response, although more research is needed to confirm this effect in humans. ^{2 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for adults with certain advanced solid tumors who have a good performance status, measurable disease, and a life expectancy of at least 12 weeks. They must not be pregnant or breastfeeding, have untreated brain metastases, recent cancer treatments, active hepatitis B/C or tuberculosis, HIV infection, autoimmune diseases or live vaccine administration within the last month.

Inclusion Criteria

Measurable disease according to Response Evaluation criteria in Solid Tumors (RECIST) Version 1.1

I can provide a sample of my tumor for testing.

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

Exclusion Criteria

Active or history of autoimmune disease

I haven't had a live vaccine in the last 4 weeks.

Prior allogeneic stem cell or organ transplantation

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase Ia: Dose Escalation

Participants receive escalating doses of RO7502175 as an IV infusion on Day 1 of each 21-day cycle until disease progression or unacceptable toxicity

Variable, based on disease progression

1 visit every 21 days

Phase Ia: Expansion

Participants receive a recommended dose of RO7502175 as an IV infusion on Day 1 of each 21-day cycle until disease progression or unacceptable toxicity

Variable, based on disease progression

1 visit every 21 days

Phase Ib: Dose Escalation

Participants receive escalating doses of RO7502175 in combination with a fixed dose of atezolizumab as an IV infusion on Day 1 of each 21-day cycle until disease progression or unacceptable toxicity

Variable, based on disease progression

1 visit every 21 days

Phase Ib: Expansion

Participants receive a recommended dose of RO7502175 in combination with a fixed dose of atezolizumab or pembrolizumab as an IV infusion on Day 1 of each 21-day cycle until disease progression or unacceptable toxicity

Variable, based on disease progression

1 visit every 21 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Atezolizumab
• RO7502175

Trial Overview The study tests RO7502175 alone and combined with Atezolizumab in patients with various solid tumors. It's conducted in two parts: first to find the right dose (dose escalation) and then to see how well it works at that dose (dose expansion).

How Is the Trial Designed?

Group I: Phase Ib: Expansion Experimental Treatment 3 Interventions

Participants with select solid tumors will receive a recommended dose of RO7502175, determined in Phase Ib Dose Escalation phase, as an IV infusion, in combination with a fixed dose of atezolizumab or pembrolizumab, as an IV infusion on Day 1 of each 21-day cycle until disease progression or unacceptable toxicity.

Group II: Phase Ib: Dose Escalation Experimental Treatment 2 Interventions

Participants in successive cohorts will receive escalating doses of RO7502175, as an IV infusion, in combination with a fixed dose of atezolizumab, as an IV infusion on Day 1 of each 21-day cycle until disease progression or unacceptable toxicity.

Group III: Phase Ia: Expansion Experimental Treatment 1 Intervention

Participants with select solid tumors will receive a recommended dose of RO7502175, determined in Phase Ia Dose Escalation phase as an IV infusion on Day 1 of each 21-day cycle until disease progression or unacceptable toxicity.

Group IV: Phase Ia: Dose Escalation Experimental Treatment 1 Intervention

Participants in successive cohorts will receive escalating doses of RO7502175, as an intravenous (IV) infusion on Day 1 of each 21-day cycle until disease progression or unacceptable toxicity.

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

Published Research Related to This Trial

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 (Tecentriq) is an FDA-approved treatment for unresectable or metastatic alveolar soft part sarcoma (ASPS), showing a 24% overall response rate in a clinical trial with 49 patients, and a durable response rate of 67% at 6 months and 42% at 12 months.

The treatment has a manageable safety profile, with common severe side effects including musculoskeletal pain (8%) and hypertension (6%), making it a viable option for patients with limited treatment alternatives for this high-risk disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab as the First Systemic Therapy Approved for Alveolar Soft Part Sarcoma. Bergsma, EJ., Elgawly, M., Mancuso, D., et al.[2023]

Atezolizumab, an immune checkpoint inhibitor, has been shown to significantly prolong overall survival in patients with advanced non-small cell lung cancer (NSCLC) who have previously received chemotherapy, based on results from the phase II POPLAR and phase III OAK trials.

The treatment is particularly effective in patients with higher PD-L1 expression, demonstrating higher objective response rates, and it has a manageable safety profile with a low incidence of immune-related adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab: A Review in Previously Treated Advanced Non-Small Cell Lung Cancer. Blair, HA.[2020]

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]

In a real-world study of 1002 patients with previously treated non-small cell lung cancer (NSCLC), atezolizumab showed an 18-month overall survival rate of 41.1%, confirming its effectiveness outside of clinical trial settings.

The safety profile was acceptable, with an overall adverse event rate of 43.9% and immune-related adverse events at 19.0%, but caution is advised for patients with poorer performance status (ECOG ≥ 2), as they had a significantly lower survival rate of 14.3%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness and Safety of Atezolizumab Monotherapy in Previously Treated Japanese Patients With Unresectable Advanced or Recurrent NSCLC: A Multicenter, Prospective, Observational Study (J-TAIL). Miura, S., Nishio, M., Akamatsu, H., et al.[2023]

Citations

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Clinical trial for Squamous Cell Carcinoma, Advanced Soli... This is a first-in-human study to evaluate the safety, tolerability, pharmacokinetics (PK), and anti-tumor activity of RO7502175

2. withpower.com withpower.com/trial/phase-1-metastatic-or-locally-advanced-solid-tumors-9-2022-f40c4

RO7502175 + Atezolizumab for Advanced Cancers What data supports the effectiveness of the drug Atezolizumab for advanced cancers? Atezolizumab has shown effectiveness in treating advanced bladder cancer ...

3. onderzoekmetmensen.nl onderzoekmetmensen.nl/en/node/53546/pdf

A PHASE Ia/Ib, OPEN LABEL, MULTICENTER, DOSE- ... RO7502175 is designed to preferentially eliminate CCR8+ Treg cells in the tumor microenvironment through antibody-dependent cell-mediated ...

4. bpspubs.onlinelibrary.wiley.com bpspubs.onlinelibrary.wiley.com/doi/10.1111/bph.16326

Preclinical and translational pharmacology of afucosylated ... Key Results. RO7502175 demonstrated selective ADCC against human CCR8+ Treg cells from dissociated tumours in vitro. In cynomolgus monkeys, ...

5. researchgate.net researchgate.net/figure/First-in-human-FiH-dose-selection-for-RO7502175-a-Minimum-anticipated-biological_fig7_378972300

First‐in‐human (FiH) dose selection for RO7502175. (a) ... Tumor drug resistance represents a major challenge in contemporary cancer therapeutics, significantly compromising the clinical efficacy of chemotherapy, ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05581004?term=RO7502175&rank=1&tab=table

A Study to Evaluate the Safety, Pharmacokinetics, and ... An unfavorable change in the health of a participant, including abnormal laboratory findings, that happens during a clinical study or within a certain amount of ...

7. cancer.gov cancer.gov/research/participate/clinical-trials/intervention/anti-ccr8-monoclonal-antibody-ro7502175?pn=1

Clinical Trials Using Anti-CCR8 Monoclonal Antibody ... A Study to Evaluate the Safety, Pharmacokinetics, and Activity of RO7502175 ... Advanced or Metastatic Solid Tumors. Status: Active. Location: 6 locations.

8. georgiacancerinfo.org georgiacancerinfo.org/clinical-trials/detail/5342

A Study to Evaluate the Safety, Pharmacokinetics, and ... Summary. This is a first-in-human study to evaluate the safety, tolerability, pharmacokinetics (PK), and anti-tumor activity of RO7502175 when administered ...

9. ancora.ai ancora.ai/en/details/NCT05581004

A Study to Evaluate the Safety, Pharmacokinetics, and ... This is a first-in-human study to evaluate the safety, tolerability, pharmacokinetics (PK), and anti-tumor activity of RO7502175 when ...