RYZ101 + Standard Treatments for Small Cell Lung Cancer

Recruiting at 25 trial locations

Overseen By RayzeBio Clinical Trials

Age: 18+

Sex: Any

Trial Phase: Phase 1

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 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: 6 weeks

49 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination treatment for individuals with extensive-stage small cell lung cancer (ES-SCLC) that has not been previously treated. Researchers aim to determine if adding a new drug, RYZ101 (also known as 225Ac-DOTATATE), to standard treatments—carboplatin, etoposide, and atezolizumab—is safe and effective against the tumor. Suitable candidates for this trial have been diagnosed with ES-SCLC, have not received more than one cycle of certain cancer therapies, and show a specific marker (SSTR+) in their cancer imaging. This trial seeks to improve treatment options for those with this aggressive form of lung cancer. 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 drug.

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.

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

Research shows that RYZ101 is being tested for safety alongside standard treatments for small cell lung cancer. Early results from previous studies suggest that RYZ101 is generally well-tolerated, meaning most people can handle it without serious problems. These studies examined different doses to determine the safest amount to use with other cancer treatments like carboplatin, etoposide, and atezolizumab.

In these trials, some side effects were reported, but they were mostly mild to moderate. This indicates that while some participants experienced reactions, they were not severe for most. As this is a new treatment in early-stage trials, researchers continue to gather information to ensure its safety for everyone.

For those considering joining a trial, it's important to know that while RYZ101 looks promising, researchers are still learning about its complete safety profile. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about RYZ101 because it introduces a novel approach to treating small cell lung cancer. Unlike standard treatments like atezolizumab, carboplatin, and etoposide, RYZ101 is a radiolabeled somatostatin analog that delivers targeted radiation directly to cancer cells. This mechanism allows for precise targeting of tumors, potentially leading to fewer side effects and greater effectiveness. By combining RYZ101 with standard care, there's hope for improved outcomes in patients who typically have limited options.

What evidence suggests that RYZ101 combined with standard treatments could be effective for small cell lung cancer?

Research shows that RYZ101, a type of radiopharmaceutical, may help treat small cell lung cancer (SCLC). In this trial, participants will receive RYZ101 with standard chemotherapy drugs such as carboplatin, etoposide, and atezolizumab. Early studies have shown that RYZ101 combined with these chemotherapy drugs shrinks tumors more effectively than the chemotherapy drugs alone. Initial results also suggest that this combination is safe and effective in slowing cancer growth. This treatment targets a specific receptor found in many SCLC tumors, potentially improving treatment outcomes. ^{1 3 4 6 7}

Who Is on the Research Team?

Petrus De Jong, MD

Principal Investigator

RayzeBio, Inc.

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Atezolizumab
• Carboplatin
• Etoposide
• RYZ101

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.

How Is the Trial Designed?

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

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?

RayzeBio, Inc.

Lead Sponsor

Trials

6

Recruited

540+

Published Research Related to This Trial

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]

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 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 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 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]

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]

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]

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]

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37616528/

Preclinical Efficacy in Small-Cell Lung Cancer RYZ101 is a highly potent, alpha-emitting radiopharmaceutical agent, and preclinical data demonstrate the potential of RYZ101 for the treatment of patients ...

2. jto.org jto.org/article/S1556-0864(23)01466-1/fulltext

P2.16-03 RYZ101 + Carboplatin + Etoposide ... We describe the design of a single-arm, open-label, phase 1b dose-escalation and dose-expansion trial of RYZ101 in combination with standard of care (SoC) ...

3. rayzebio.com rayzebio.com/wp-content/uploads/2024/09/RayzeBio-WCLC-2024-poster-UPLOAD.pdf

RYZ101 (225Ac-DOTATATE) + carboplatin + etoposide + ... Preliminary data show that the safety profile of RYZ101 in ... small cell lung cancer (SCLC) in around 48% of samples by IHC1 and ...

4. aacrjournals.org aacrjournals.org/mct/article/22/12/1434/730266/RYZ101-Ac-225-DOTATATE-Opportunity-beyond

RYZ101 (Ac-225 DOTATATE) Opportunity beyond ... Furthermore, RYZ101 showed superior antitumor efficacy compared with SCLC SOC carboplatin and etoposide at clinically relevant doses, and RYZ101 in combination ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S1556086425011256

OA13.03 RYZ101 (225Ac-DOTATATE) + Carboplatin ... Here we describe preliminary safety data from a single-arm, open-label, phase 1b dose-escalation and dose-expansion trial of RYZ101 in combination with standard ...

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1556086424012528

P1.13A.09 RYZ101 (225Ac-DOTATATE) + Carboplatin + ... Here we describe preliminary safety data from a single-arm, open-label, phase 1b dose-escalation and dose-expansion trial of RYZ101 in combination with standard ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05595460

NCT05595460 | Study of RYZ101 in Combination With ... This study aims to determine the safety, preliminary antitumor activity, and pharmacokinetics (PK) of RYZ101 in combination with standard of care (SoC) therapy ...