ROSE12 + Atezolizumab for Solid Tumor Cancer

Recruiting at 3 trial locations

Overseen By Clinical trials information

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Chugai Pharmaceutical

Must not be taking: Investigational therapy, Anti-cancer therapy

Disqualifiers: Cardiovascular, Liver, Autoimmune, CNS, 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

219 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety of a new treatment called ROSE12, both alone and with atezolizumab (an immunotherapy drug), for individuals with advanced solid tumors. Researchers aim to understand how the body processes these drugs and determine the optimal doses. The study consists of several parts: testing different doses, examining tumor samples through biopsies, and expanding to more patients. Those with advanced solid tumors who have not responded to other treatments might be suitable for this trial. As a Phase 1 trial, this 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 investigational or anti-cancer therapy at least 28 days before starting the study drug. The protocol does not specify about other medications, so 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 ROSE12, when used alone in patients with solid tumors, can cause common side effects such as tiredness, loss of appetite, and nausea. More serious side effects might include lung inflammation and liver problems. However, information remains limited because ROSE12 is still under investigation in early clinical trials.

For those considering ROSE12 with atezolizumab, here is some background on atezolizumab. It is already used for certain cancers, like advanced bladder cancer and non-small cell lung cancer. In these cases, it has improved response rates and survival. Atezolizumab alone is generally considered safe, but combining it with ROSE12 is still under careful study to fully understand its safety.

Since this study is in its early stages, the main goal is to determine the safety of these treatments and how the body processes them. Participants should be aware that much remains to be learned about these treatments. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about ROSE12 and atezolizumab for solid tumors because they offer a novel approach to treatment. Unlike standard options like chemotherapy, which generally attack all rapidly dividing cells, ROSE12 is designed to target specific pathways involved in tumor growth. When combined with atezolizumab, an immunotherapy drug that boosts the body's natural defenses to fight cancer, there is potential for a more effective and targeted treatment. This unique combination aims to enhance the immune response while directly interfering with cancer cell proliferation, which could lead to better outcomes for patients with solid tumors.

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

Research shows that ROSE12 is a new antibody that specifically targets tumors. It focuses on cancer cells while sparing healthy cells, potentially leading to fewer side effects. Studies have found ROSE12 effective against solid tumors. In this trial, some participants will receive ROSE12 alone, while others will receive a combination of ROSE12 and Atezolizumab.

Atezolizumab, the other treatment in this study, has already proven effective for certain cancers, such as advanced bladder cancer and non-small cell lung cancer. It helps patients live longer and respond better to treatment.

When used together, ROSE12 and Atezolizumab might enhance the immune system's ability to fight cancer more effectively. Early research supports testing this combination for solid tumors to improve treatment outcomes. ^{1 3 4 6 7}

Who Is on the Research Team?

Sponsor Chugai Pharmaceutical Co.Ltd

Principal Investigator

[e-mail]

Are You a Good Fit for This Trial?

Adults (18+) with advanced solid tumors, who have tried standard treatments without success or for whom no standard treatment exists. They must be in relatively good health otherwise (ECOG PS 0 or 1), have a life expectancy of at least 12 weeks, and be able to provide tumor samples. People with severe allergies to certain antibodies, recent cancer treatments, unresolved side effects from past therapies (except hair loss and some hormone issues), brain metastases needing treatment, significant heart/liver disease, history of severe immune reactions to immunotherapy, uncontrolled pain/effusions/autoimmune diseases or another cancer within the last five years cannot join.

Inclusion Criteria

I am fully active or can carry out light work.

I have a tumor that can be easily reached for a biopsy.

Life expectancy >= 12 weeks

Exclusion Criteria

I have a brain tumor or cancer spread to my brain that needs treatment.

I have ongoing side effects from cancer immunotherapy, except for stable hormone issues, vitiligo, or hair loss.

I have previously been treated with a drug that targets Treg cells.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose-escalation

Participants receive ROSE12 as a single agent and in combination with atezolizumab at escalated doses to determine the maximum tolerated dose and recommended dose.

21 days per cycle

Multiple visits per cycle for dose administration and monitoring

Biopsy

Serial biopsies are conducted to evaluate biomarkers while patients receive ROSE12 and atezolizumab.

Concurrent with dose-escalation

Expansion

Participants receive ROSE12 and atezolizumab at the recommended dose to further evaluate safety and preliminary anti-tumor activity.

Until disease progression or unacceptable toxicity

Follow-up

Participants are monitored for safety and effectiveness after treatment completion.

Up to 43 months

What Are the Treatments Tested in This Trial?

Interventions

• Atezolizumab
• ROSE12

Trial Overview The trial is testing ROSE12's safety and how it moves through the body both alone and combined with other anti-tumor agents like Atezolizumab in patients with solid tumors. It has three parts: finding the right dose ('dose-escalation'), checking biomarkers ('biopsy part'), and offering it to more people once safe doses are found ('expansion part').

How Is the Trial Designed?

Group I: Part E: Expansion part of Phase Ib in patients with selected solid tumors Experimental Treatment 2 Interventions

Patients will receive ROSE12 and atezolizumab as a IV infusion at the recommended dose.

Group II: Part D: Biopsy part of Phase Ib Experimental Treatment 2 Interventions

Serial biopsy will be conducted with patients who will receive ROSE12 and atezolizumab as a IV infusion at escalated doses.

Group III: Part C: Dose-escalation part of Phase Ib Experimental Treatment 2 Interventions

Patients will receive ROSE12 and atezolizumab as a IV infusion at escalated doses.

Group IV: Part B: Biopsy part of Phase Ia Experimental Treatment 1 Intervention

Serial biopsy will be conducted with patients who will receive ROSE12 as a IV infusion at escalated doses.

Group V: Part A: Dose-escalation part of Phase Ia Experimental Treatment 1 Intervention

Patients will receive ROSE12 as a IV infusion at escalated doses.

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?

Chugai Pharmaceutical

Lead 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

Published Research Related to This Trial

Atezolizumab, a PD-L1 blocking antibody, shows higher rates of objective response, progression-free survival, and overall survival when used as a first-line therapy in chemotherapy-naïve patients with metastatic non-small cell lung cancer (NSCLC), compared to its use in later treatment lines.

The review included 15 ongoing studies, with 5 reporting results, indicating that atezolizumab is being explored in various treatment combinations and settings, suggesting its potential as a versatile first-line treatment option for NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab for the First-Line Treatment of Non-small Cell Lung Cancer (NSCLC): Current Status and Future Prospects. Ryu, R., Ward, KE.[2023]

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]

Atezolizumab significantly improved overall survival in patients with previously treated non-small-cell lung cancer compared to docetaxel, with median survival times of 13.8 months versus 9.6 months, respectively.

The safety profile of atezolizumab was favorable, with only 15% of patients experiencing grade 3 or 4 adverse events, compared to 43% in the docetaxel group, indicating it may be a safer treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. Rittmeyer, A., Barlesi, F., Waterkamp, D., et al.[2022]

Atezolizumab significantly improves overall survival in patients with metastatic non-small cell lung cancer (mNSCLC), with median survival times of 13.8 months in the atezolizumab group compared to 9.6 months in the docetaxel group in the OAK trial.

The treatment has an acceptable safety profile, with common side effects including fatigue and decreased appetite, and serious immune-related adverse events occurring in a small percentage of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

U.S. Food and Drug Administration Approval Summary: Atezolizumab for Metastatic Non-Small Cell Lung Cancer. Weinstock, C., Khozin, S., Suzman, D., et al.[2022]

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 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 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, 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]

Citations

1. jitc.bmj.com jitc.bmj.com/content/12/Suppl_2/A1039

920 ROSE12, a novel anti-CTLA-4 switch antibody with ... ROSE12 is a novel FcγR affinity-enhanced anti-CTLA-4 switch antibody with potent anti-tumor efficacy and a wide therapeutic window due to its tumor-selective ...

2. aacrjournals.org aacrjournals.org/cancerres/article/85/8_Supplement_1/6063/758677/Abstract-6063-ROSE12-a-novel-anti-CTLA-4-Switch

Abstract 6063: ROSE12, a novel anti-CTLA-4 Switch antibody ... These results strongly support the clinical testing of ROSE12 in the treatment of solid tumors. Currently, ROSE12 is undergoing a phase 1 ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05907980

A Phase I Study of ROSE12 Alone and in Combination ... This is a Phase Ia/Ib open-label, dose-escalation study to evaluate the safety and pharmacokinetics of ROSE12 as a single agent and in combination with ...

4. withpower.com withpower.com/trial/phase-1-neoplasms-4-2023-c3156

ROSE12 + Atezolizumab for Solid Tumor Cancer Atezolizumab has shown effectiveness in treating advanced bladder cancer and non-small cell lung cancer, with improved response rates and survival compared to ...

5. aacrjournals.org aacrjournals.org/cancerres/article/85/8_Supplement_1/6066/758676

Preclinical evaluation of toxicity reduction for ROSE12, a novel ... Our study suggests that ROSE12, which has ATP dependency, may mitigate colonic toxicity by avoiding the depletion of Tregs in colon lamina ...

6. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2023-10772

A Phase I Study of ROSE12 Alone and in Combination ... This is a Phase Ia/Ib open-label, dose-escalation study to evaluate the safety and pharmacokinetics of ROSE12 as a single agent and in combination with other ...

7. clinicaltrials.gastriccancer.org clinicaltrials.gastriccancer.org/en-US/trial/listing/420555

A Phase I Study of ROSE12 Alone and in Combination ... This is a Phase Ia/Ib open-label, dose-escalation study to evaluate the safety and pharmacokinetics of ROSE12 as a single agent and in ...