RYZ101 + Standard Treatments for Small Cell Lung Cancer

Recruiting in Palo Alto (17 mi)

+26 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: RayzeBio, Inc.

Must be taking: Carboplatin, Etoposide, Atezolizumab

Must not be taking: Antibiotics, Vaccines

Disqualifiers: Autoimmune disease, Severe infection, Cardiovascular disease, others

No Placebo Group

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug, RYZ101, combined with standard cancer treatments in patients with a specific type of untreated lung cancer. The new drug aims to target certain receptors on cancer cells, while the other drugs work to kill the cancer cells and help the immune system fight them.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on antibiotics or have recently had a live vaccine, you may need to wait before starting the trial.

What data supports the effectiveness of the drug combination RYZ101, Atezolizumab, Carboplatin, and Etoposide for treating small cell lung cancer?

Research shows that adding atezolizumab to carboplatin and etoposide significantly improves survival in patients with extensive-stage small cell lung cancer compared to chemotherapy alone. This combination is well-tolerated and has become a standard treatment option. ^{1 2 3 4 5}

Is the combination of RYZ101 and standard treatments for small cell lung cancer safe for humans?

The combination of atezolizumab (Tecentriq) with carboplatin and etoposide has been generally well tolerated in patients with extensive-stage small cell lung cancer, with no new safety concerns beyond those known for the individual drugs. Common side effects include blood-related issues, skin rash, and low thyroid function, but it did not negatively affect patients' quality of life. ^{1 3 5 6 7}

What makes the drug RYZ101 combined with standard treatments unique for small cell lung cancer?

The drug RYZ101 combined with standard treatments for small cell lung cancer is unique because it includes atezolizumab, an immune checkpoint inhibitor that has been shown to improve survival when added to the traditional chemotherapy regimen of carboplatin and etoposide. This combination represents a newer approach that enhances the body's immune response against cancer cells, offering a significant advancement over previous treatments that relied solely on chemotherapy. ^{3 5 8 9 10}

Research Team

Ye Yuan, MD

Principal Investigator

RayzeBio, Inc.

Eligibility Criteria

This trial is for adults with untreated ES-SCLC that expresses somatostatin receptors. Participants must have adequate organ function, no severe allergies to certain drugs or cell products, and not be pregnant or breastfeeding. They should not have had major surgery recently, active infections like TB or hepatitis, significant heart disease, other cancers in the last 3 years (with some exceptions), or a history of severe allergic reactions.

Inclusion Criteria

Able to read and/or understand the details of the study and provide written informed consent prior to any study-specific assessments and procedures commence

I am eligible for standard cancer treatment including Carboplatin, Etoposide, and Atezolizumab.

WOCBP must have a negative serum pregnancy test within 48 hours prior to the first dose of study drug and agree to use barrier contraception and a second form of highly effective contraception or total abstinence

Exclusion Criteria

I have not received a live vaccine in the last 4 weeks.

I am unable or unwilling to follow the study's requirements.

I have an autoimmune disease or symptoms suggesting one.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive RYZ101 in combination with standard of care therapy (carboplatin + etoposide + atezolizumab)

6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

50 months

Treatment Details

Interventions

• Atezolizumab (Monoclonal Antibodies)
• Carboplatin (Other)
• Etoposide (Other)
• RYZ101 (Other)

Trial Overview The study tests RYZ101 at various doses combined with standard chemotherapy (carboplatin + etoposide) and immunotherapy (atezolizumab) in patients with SSTR+ ES-SCLC. It aims to assess safety, how well it works against cancer cells, and how the body processes the drug.

Participant Groups

Group I: RYZ101 + SoC Experimental Treatment 7 Interventions

RYZ101 (Actinium 225 radiolabeled somatostatin analog (SSA)) 6.5 MBq/175 μCi in combination with standard of care (SoC) carboplatin + etoposide + atezolizumab

Who Is Running the Clinical Trial?

RayzeBio, Inc.

Lead Sponsor

Trials

6

Recruited

540+

Findings from Research

In a study of 65 patients with extensive-disease small-cell lung cancer, the combination of atezolizumab, carboplatin, and etoposide showed a high response rate of 73.8%, with 80.5% in elderly patients (median age 74 years).

Despite some significant hematological toxicities, such as decreased neutrophil counts in 61.1% of elderly patients, the treatment demonstrated acceptable safety and efficacy, suggesting it could be a preferred standard treatment for elderly patients with this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world data of atezolizumab plus carboplatin and etoposide in elderly patients with extensive-disease small-cell lung cancer. Shiono, A., Imai, H., Wasamoto, S., et al.[2023]

The combination of atezolizumab, a PD-L1 inhibitor, with platinum-based chemotherapy significantly improves overall survival in patients with extensive-stage small cell lung cancer compared to chemotherapy alone.

This research suggests that this combination therapy could become a new first-line treatment option for patients suffering from this aggressive form of lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Study: Atezolizumab Improves Survival in SCLC. [2019]

Atezolizumab, combined with carboplatin and etoposide, significantly improves overall survival and progression-free survival in patients with extensive-stage small cell lung cancer, based on data from the IMpower133 trial involving previously untreated patients.

The treatment regimen is generally well tolerated, with no new safety concerns identified, and it does not negatively impact patients' quality of life, making it a valuable first-line therapy option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab: A Review in Extensive-Stage SCLC. Frampton, JE.[2021]

In a study of 99 previously untreated patients with extensive disease small cell lung cancer (ED-SCLC), adding atezolizumab to the standard carboplatin and etoposide regimen significantly improved overall survival, extending it to 20.8 months compared to 12.1 months for those receiving carboplatin and etoposide alone.

While there was no significant difference in progression-free survival between the two treatment groups, certain subgroups (such as older patients, males, and those with better health status) showed particularly enhanced survival benefits from the addition of atezolizumab, indicating its potential for personalized treatment approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab addition to platinum doublet: evaluating survival outcomes for patients with extensive disease small cell lung cancer. Kubo, S., Kobayashi, N., Matsumoto, H., et al.[2023]

In a study of 225 patients with extensive-stage small-cell lung cancer, those treated with atezolizumab combined with etoposide/platinum (EP) had a longer progression-free survival (PFS) of 7.10 months compared to 6.50 months for those receiving EP alone, indicating enhanced efficacy of the combination treatment.

The most common adverse event in the atezolizumab group was bone marrow suppression (58.6%), with immune-related adverse events occurring in 14.3% of patients, suggesting that while atezolizumab improves outcomes, it also carries a risk of significant side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical outcomes of atezolizumab in combination with etoposide/platinum for treatment of extensive-stage small-cell lung cancer: A real-world, multicenter, retrospective, controlled study in China. Chen, H., Ma, X., Liu, J., 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 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 the phase III SKYSCRAPER-02 study involving 490 patients with untreated extensive-stage small-cell lung cancer, the addition of tiragolumab to atezolizumab and chemotherapy did not significantly improve progression-free survival (PFS) or overall survival (OS).

The combination treatment was well tolerated, with similar rates of immune-mediated adverse events between the tiragolumab and control groups, indicating no new safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SKYSCRAPER-02: Tiragolumab in Combination With Atezolizumab Plus Chemotherapy in Untreated Extensive-Stage Small-Cell Lung Cancer. Rudin, CM., Liu, SV., Soo, RA., et al.[2023]

The combination of the anti-PD-1 antibody budigalimab and the antibody-drug conjugate Rova-T was found to be tolerated in 31 patients with previously treated small cell lung cancer (SCLC), with common side effects including pleural effusion, fatigue, and cough.

This combination therapy showed an overall response rate of 24.1%, with one complete response and six partial responses, indicating promising efficacy despite the discontinuation of Rova-T's development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, pharmacokinetics, and efficacy of budigalimab with rovalpituzumab tesirine in patients with small cell lung cancer. Calvo, E., Spira, A., Miguel, M., et al.[2022]

The combination of anti-PD1/PD-L1 immunotherapy with chemotherapy (carboplatin plus etoposide) significantly improves overall survival in patients with extensive-disease small-cell lung cancer (ED-SCLC), with a hazard ratio of 0.746 indicating a 25% reduction in the risk of death compared to chemotherapy alone.

Among various treatment combinations, nivolumab plus chemotherapy was identified as the most effective option for improving both overall survival and progression-free survival, outperforming the anti-CTLA-4 approach in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line immune-checkpoint inhibitor treatment in extensive-disease small-cell lung cancer: A classical and network meta-analysis. Mutlu, H., Bozcuk, H., Artaç, M., et al.[2023]

References

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

Real-world data of atezolizumab plus carboplatin and etoposide in elderly patients with extensive-disease small-cell lung cancer. [2023]

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

Study: Atezolizumab Improves Survival in SCLC. [2019]

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

Atezolizumab: A Review in Extensive-Stage SCLC. [2021]

4. Germany pubmed.ncbi.nlm.nih.gov

Atezolizumab addition to platinum doublet: evaluating survival outcomes for patients with extensive disease small cell lung cancer. [2023]

5. China pubmed.ncbi.nlm.nih.gov

Clinical outcomes of atezolizumab in combination with etoposide/platinum for treatment of extensive-stage small-cell lung cancer: A real-world, multicenter, retrospective, controlled study in China. [2022]

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

Atezolizumab as the First Systemic Therapy Approved for Alveolar Soft Part Sarcoma. [2023]

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

Atezolizumab: First Global Approval. [2019]

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

SKYSCRAPER-02: Tiragolumab in Combination With Atezolizumab Plus Chemotherapy in Untreated Extensive-Stage Small-Cell Lung Cancer. [2023]

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

Safety, pharmacokinetics, and efficacy of budigalimab with rovalpituzumab tesirine in patients with small cell lung cancer. [2022]

10. India pubmed.ncbi.nlm.nih.gov

First-line immune-checkpoint inhibitor treatment in extensive-disease small-cell lung cancer: A classical and network meta-analysis. [2023]