LB-100 + Chemotherapy + Immunotherapy for Small Cell Lung Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: City of Hope Medical Center

Must not be taking: Corticosteroids, Antiepileptics, Warfarin, others

Disqualifiers: NSCLC, Cardiac condition, CNS metastases, 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments for individuals with untreated extensive-stage small cell lung cancer. It examines whether adding a drug called LB-100 to standard chemotherapy and immunotherapy enhances treatment effectiveness. Researchers believe LB-100 increases the vulnerability of cancer cells, improving the efficacy of these drugs. This trial may suit those diagnosed with this specific lung cancer type who have not previously received chemotherapy or immunotherapy. 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 stopping certain medications before starting, such as those that prolong the QT interval, nephrotoxic compounds, warfarin, certain antiepileptic drugs, and strong P-glycoprotein inhibitors, at least 7 days before the first dose. If you are on any of these, you may need to stop or switch them.

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

Research has shown that atezolizumab is generally safe when combined with chemotherapy for small cell lung cancer. In earlier studies, only 3% of patients experienced serious immune-related lung problems, which are rare. Atezolizumab is usually well-tolerated and can improve treatment outcomes when used with chemotherapy.

For LB-100, less safety information is available. This study is in its early stages, with the primary goal of identifying side effects and determining the optimal dose. As a result, some uncertainties exist regarding how well patients tolerate LB-100. However, LB-100 is under investigation for its potential to enhance the effectiveness of standard cancer treatments.

The combination of these treatments is being studied for both effectiveness and safety. Researchers will closely monitor participants to manage any potential side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination treatment of LB-100 with atezolizumab, carboplatin, and etoposide for small cell lung cancer because it introduces a novel approach to enhance the effectiveness of existing therapies. LB-100 is a unique compound that inhibits protein phosphatase 2A, potentially making cancer cells more sensitive to chemotherapy and immunotherapy. This could improve outcomes compared to the standard regimen of carboplatin and etoposide with atezolizumab alone. By potentially boosting the immune response and increasing the efficacy of chemotherapy, this combination therapy offers a promising new strategy for a tough-to-treat cancer.

What evidence suggests that this trial's treatments could be effective for small cell lung cancer?

Research has shown that adding atezolizumab to chemotherapy can improve outcomes for small cell lung cancer. One study demonstrated that patients lived longer, with a median survival of 12.3 months when atezolizumab was used. Another study found that combining atezolizumab with chemotherapy delayed cancer progression for 5.2 months, compared to 4.3 months without it. In this trial, participants will receive a combination of LB-100, atezolizumab, carboplatin, and etoposide. LB-100 is believed to enhance chemotherapy effectiveness by blocking a protein called PP2A, making cancer cells more sensitive to treatment. Overall, these treatments together show promise in fighting extensive-stage small cell lung cancer. ^{2 3 4 5 6}

Who Is on the Research Team?

Ravi Salgia

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

This trial is for adults with untreated extensive-stage small cell lung cancer. Participants must have proper liver, kidney, and blood function, not be pregnant or breastfeeding, agree to use contraception if of childbearing potential, and have no prior treatments for SCLC. They should also have a life expectancy of at least 12 weeks and an ECOG performance status of 0-2.

Inclusion Criteria

My lung cancer is confirmed to be extensive-stage small cell type.

Your bilirubin levels must be within a certain range to be eligible.

I am a woman not able to have children, not pregnant, and not breastfeeding.

Exclusion Criteria

I have been diagnosed with congenital long QT syndrome.

I haven't taken any kidney-damaging drugs in the last week.

I have a history of lung scarring or inflammation but not due to radiation.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction

Patients receive LB-100, atezolizumab, carboplatin, and etoposide. Treatment repeats every 21 days for 4 cycles.

12 weeks

4 cycles, each with multiple visits for infusions

Maintenance

Patients receive LB-100 and atezolizumab. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Variable, based on disease progression

Follow-up

Participants are monitored for safety and effectiveness after treatment completion. Follow-up occurs every 6-8 weeks for those without disease progression.

Up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• Atezolizumab
• Carboplatin
• Etoposide
• LB-100

Trial Overview The study tests the combination of LB-100 with standard chemotherapy drugs (carboplatin and etoposide) plus immunotherapy drug Atezolizumab. It aims to find the best dose of LB-100 that enhances the effectiveness of these drugs in killing tumor cells by blocking a protein called PP2A.

How Is the Trial Designed?

Group I: Treatment (LB-100, carboplatin, etoposide, atezolizumab) Experimental Treatment 4 Interventions

INDUCTION: Patients receive LB-100 IV over 15 minutes on days 1 and 3, atezolizumab IV over 30-60 minutes on day 1, carboplatin IV over 30-60 minutes on day 1, and etoposide IV over 60 minutes on days 1-3. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE: After completion of induction therapy, patients receive LB-100 IV over 15 minutes on days 1 and 3 and atezolizumab IV over 30 minutes on day 1. Cycles repeat every 21 days in the absence of 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?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

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 FDA approved atezolizumab, a PD-L1 inhibitor, in combination with carboplatin and etoposide as a first-line treatment for small cell lung cancer, highlighting its role in enhancing therapy options.

This approval was supported by the phase III IMpower133 trial, which demonstrated that the addition of atezolizumab significantly improved both overall survival and progression-free survival in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-Line Atezolizumab OK'd for SCLC. [2020]

Atezolizumab combined with chemotherapy showed promising efficacy in treating advanced, treatment-naïve non-small-cell lung cancer (NSCLC), with overall response rates of 36% to 68% across different chemotherapy regimens in a study of 76 patients.

The treatment was generally well tolerated, although common severe side effects included neutropenia and anemia, indicating a manageable safety profile for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term survival follow-up of atezolizumab in combination with platinum-based doublet chemotherapy in patients with advanced non-small-cell lung cancer. Liu, SV., Camidge, DR., Gettinger, SN., et al.[2022]

Atezolizumab combined with carboplatin and etoposide was effective in treating a 75-year-old woman with advanced small cell lung cancer and an ECOG Performance Status of 2, leading to complete regression after 4 cycles of treatment.

Despite experiencing some adverse effects like anemia and thrombocytopenia, the patient's therapy was continued due to positive imaging results, highlighting the potential for immunochemotherapy in patients typically excluded from clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A 75-Year-Old Female Smoker with Advanced Small-Cell Lung Cancer and Eastern Cooperative Oncology Group Performance Status 2 who Responded to Combination Immunochemotherapy with Atezolizumab, Etoposide, and Carboplatin. Dębczyński, M., Mojsak, D., Kuklińska, B., et al.[2022]

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]

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 124 patients with treatment-naïve, metastatic nonsquamous PD-L1-positive non-small cell lung cancer, the combination of atezolizumab with carboplatin and nab-paclitaxel showed significantly improved overall survival (19.9 months) and progression-free survival (8.5 months) compared to carboplatin and nab-paclitaxel alone (14.8 months and 5.1 months, respectively).

While the combination therapy had a higher incidence of manageable adverse events like neutropenia and anemia, it still demonstrated a tolerable safety profile, suggesting it could be an effective first-line treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carboplatin and nab-paclitaxel chemotherapy with or without atezolizumab as front-line management for treatment-naïve metastatic nonsquamous non-small cell lung cancer with PD-L1 staining: a retrospective study. Xu, B., Cheng, H., Li, K., et al.[2023]

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 involving 403 patients with extensive-stage small-cell lung cancer, adding atezolizumab to carboplatin and etoposide significantly improved overall survival (OS) from 10.3 months to 12.3 months compared to placebo, indicating its efficacy as a first-line treatment.

The addition of atezolizumab showed a tolerable safety profile and provided benefits regardless of patients' PD-L1 or blood-based tumor mutational burden status, suggesting it can be effective across different patient biomarker profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Updated Overall Survival and PD-L1 Subgroup Analysis of Patients With Extensive-Stage Small-Cell Lung Cancer Treated With Atezolizumab, Carboplatin, and Etoposide (IMpower133). Liu, SV., Reck, M., Mansfield, AS., et al.[2022]

A phase I trial presented in 2015 indicates that rovalpituzumab tesirine, an experimental antibody-drug conjugate, shows potential effectiveness against recurrent small cell lung cancer, a type of cancer with limited treatment options.

This trial highlights the promise of rovalpituzumab tesirine as a new therapeutic approach for patients suffering from this challenging form of lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ADC Shows Effectiveness in SCLC. [2015]

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]

Citations

1. tecentriq-hcp.com tecentriq-hcp.com/sclc/efficacy/clinical-trial-results.html

IMpower133 efficacy results in 1L ES-SCLC Adding TECENTRIQ® (atezolizumab) to carbo/etop significantly improved median PFS1. 5.2-month median PFS vs 4.3 months with placebo + carbo/etop (HR=0.77*; ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37871898/

The Real-World Outcome of First Line Atezolizumab in ... We provided evidence of the favorable real-world effectiveness and safety of atezolizumab plus chemotherapy in ES-SCLC patients.

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa1809064

First-Line Atezolizumab plus Chemotherapy in Extensive- ... Despite response rates of 60 to 65%, limited progress has been made in more than two decades; outcomes remain poor, with a median overall ...

4. tecentriq.com tecentriq.com/sclc/results/how-tecentriq-may-help.html

Imagine if you had more time to live your life More patients lived longer with TECENTRIQ + chemotherapy ... Median overall survival (OS) was 12.3 months for patients taking TECENTRIQ® (atezolizumab.

5. sciencedirect.com sciencedirect.com/science/article/pii/S0169500223009170

Results of the IFCT-1905 CLINATEZO real-world study Atezolizumab plus chemotherapy improves overall survival in 1st-line treatment of extensive SCLC. IFCT-1905 CLINATEZO studied consecutive patients receiving ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31959349/

Safety and Patient-Reported Outcomes of Atezolizumab ... These data demonstrate the positive benefit-risk profile of first-line atezolizumab plus CP/ET in ES-SCLC and further support this regimen as a new standard of ...