M9466 + Carboplatin for Solid Tumors

Recruiting at 2 trial locations

Overseen By Communication Center

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: EMD Serono Research & Development Institute, Inc.

Disqualifiers: Recent malignancy, Brain 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: Unknown

54 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

What data supports the effectiveness of the drug combination Atezolizumab, Carboplatin, and Etoposide for treating solid tumors?

Research shows that the combination of Atezolizumab, Carboplatin, and Etoposide has been effective in treating small-cell lung cancer, with some patients experiencing complete regression of the disease. Additionally, studies indicate that this combination can prolong survival in patients with certain types of lung cancer. ^{1 2 3 4 5}

Is the combination of M9466 (Atezolizumab) and Carboplatin safe for humans?

The combination of Atezolizumab (also known as M9466) and Carboplatin has been studied in various cancers, showing an acceptable safety profile. Common side effects include fatigue, decreased appetite, and nausea, while more serious effects like pneumonia and liver inflammation are less common. In some cases, adjustments in dosage were necessary to manage side effects. ^{4 5 6 7 8}

What makes the drug combination of M9466, Carboplatin, and other agents unique for treating solid tumors?

This treatment is unique because it combines atezolizumab, an immune checkpoint inhibitor, with carboplatin and etoposide, which are chemotherapy drugs, to enhance the immune system's ability to fight cancer while directly targeting cancer cells. This combination has shown effectiveness in treating small cell lung cancer, especially in patients with limited treatment options, such as those with poor physical health or undergoing dialysis. ^{1 3 4 5 6}

What is the purpose of this trial?

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamic, and preliminary clinical activity of M9466 in combinations with carboplatin in advanced or metastatic refractory solid tumor and with the standard of care (carboplatin, etoposide, and atezolizumab) in treatment-naïve ES-SCLC. The results will support any investigation of carboplatin-based combination anticancer treatments with M9466 as well as the selection of a RP2D of M9466 in combination with carboplatin, etoposide, and atezolizumab for a subsequent ES-SCLC study.

Research Team

Medical Responsible

Principal Investigator

EMD Serono Research & Development Institute, Inc.

Eligibility Criteria

This trial is for adults with advanced solid tumors that haven't responded to treatment, or those newly diagnosed with ES-SCLC who haven't started treatment. Participants must be able to handle the side effects of chemotherapy.

Inclusion Criteria

My blood, liver, and kidney functions meet the required levels.

Other protocol defined inclusion criteria could apply

My cancer has spread, doesn't respond to standard treatments, and I've had 3 or fewer previous cancer treatments.

Exclusion Criteria

My brain metastases are under control without needing steroids.

Life expectancy of less than 3 months

My side effects from previous treatments are mild or stable.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Finding

Participants receive M9466 in combination with carboplatin to determine the optimal dose

8 weeks

Dose Reassessment

Participants receive M9466 with carboplatin, etoposide, and atezolizumab to reassess dosing

8 weeks

Dose Expansion

Participants receive M9466 with carboplatin, etoposide, and atezolizumab to expand on dose findings

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Atezolizumab
• Carboplatin
• Etoposide
• M9446
• M9466

Trial Overview The study tests M9466 combined with carboplatin in patients with refractory solid tumors and adds standard care (carboplatin, etoposide, atezolizumab) for new ES-SCLC cases. It aims to find a safe dose of M9466 and see how well it works.

Participant Groups

Group I: Module 2 Part B (Dose Expansion): M9466 + Carboplatin + Etoposide + Atezolizumab Experimental Treatment 4 Interventions

Group II: Module 2 Part A (Dose Reassessment): M9466 + Carboplatin + Etoposide + Atezolizumab Experimental Treatment 4 Interventions

Group III: Module 1 (Dose Finding): M9466 + Carboplatin Experimental Treatment 2 Interventions

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?

EMD Serono Research & Development Institute, Inc.

Lead Sponsor

Trials

86

Recruited

22,700+

Miguel Fernández Alcalde

EMD Serono Research & Development Institute, Inc.

Chief Executive Officer

Bachelor’s Degree in Pharmacy from the University Complutense in Madrid, MBA from the University of Alcalá de Henares, Master’s Degree in Management from IESE Business School

Danny Bar-Zohar

EMD Serono Research & Development Institute, Inc.

Chief Medical Officer since 2022

MD

Merck KGaA, Darmstadt, Germany

Industry Sponsor

Trials

449

Recruited

122,000+

Danny Bar-Zohar

Merck KGaA, Darmstadt, Germany

Chief Medical Officer since 2022

MD

Belén Garijo

Merck KGaA, Darmstadt, Germany

Chief Executive Officer since 2021

MD

Findings from Research

Atezolizumab combined with chemotherapy (ABCP or ACnP) has been shown to significantly improve progression-free survival (PFS) and overall survival (OS) in chemotherapy-naïve patients with metastatic nonsquamous non-small cell lung cancer (NSCLC), based on the IMpower150 and IMpower130 studies.

Both treatment regimens (ABCP and ACnP) demonstrated manageable safety profiles, with most immune-related side effects being mild to moderate and reversible, making them promising first-line options for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab First-Line Combination Therapy: A Review in Metastatic Nonsquamous NSCLC. Dhillon, S., Syed, YY.[2020]

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]

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 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]

An 80-year-old male with extensive-stage small cell lung cancer safely received a combination of carboplatin, etoposide, and atezolizumab while undergoing hemodialysis, indicating that this treatment can be feasible for patients with similar conditions.

Despite experiencing grade 4 neutropenia and leukopenia during the first cycle, the patient was able to continue treatment with adjusted dosages, and no severe non-haematological adverse events were reported after four cycles, demonstrating a positive response to the therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemotherapy plus atezolizumab for a patient with small cell lung cancer undergoing haemodialysis: a case report and review of literature. Imaji, M., Fujimoto, D., Kato, M., et al.[2021]

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, 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]

References

1. Germany pubmed.ncbi.nlm.nih.gov

[Chemotherapy of small cell bronchial cancer with a combination of carboplatin, vincristine and etoposide]. [2015]

2. France pubmed.ncbi.nlm.nih.gov

Atezolizumab First-Line Combination Therapy: A Review in Metastatic Nonsquamous NSCLC. [2020]

3. United States 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. [2022]

4. Germany 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. [2023]

5. 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]

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

Chemotherapy plus atezolizumab for a patient with small cell lung cancer undergoing haemodialysis: a case report and review of literature. [2021]

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

U.S. Food and Drug Administration Approval Summary: Atezolizumab for Metastatic Non-Small Cell Lung Cancer. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Atezolizumab for use in PD-L1-positive unresectable, locally advanced or metastatic triple-negative breast cancer. [2020]