M9466 + Carboplatin for Solid Tumors

No longer 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effects of a new drug, M9466 (also known as HRS-1167), combined with carboplatin and other standard treatments for certain advanced or hard-to-treat solid tumors, including extensive stage small cell lung cancer (ES-SCLC). It explores how these drugs work together and aims to find the best dose for future studies. Suitable participants have either advanced solid tumors unresponsive to standard treatments or are newly diagnosed with ES-SCLC and can receive the typical treatment for it. 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 drug.

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.

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

Studies have shown that the combination of atezolizumab, carboplatin, and etoposide has been tested in patients with lung cancer and is generally considered safe. Common side effects include tiredness, nausea, and hair loss.

Research indicates that M9466 combined with carboplatin is also generally safe for various cancers. Common side effects resemble those of other cancer treatments, such as fatigue and nausea. As these treatments remain in early testing, the researchers continue to gather information about their safety and patient tolerance. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of M9466 with Carboplatin and other agents because it represents a fresh approach to treating solid tumors. Unlike traditional chemotherapy, which targets rapidly dividing cells indiscriminately, M9466 is designed to work more precisely by enhancing the immune system's ability to fight cancer. This combination includes Atezolizumab, an immune checkpoint inhibitor, which can help the body's T-cells detect and destroy cancer cells more effectively. Additionally, Etoposide and Carboplatin are well-known chemotherapy agents that work by damaging the DNA of cancer cells, but when combined with M9466, they may have a synergistic effect, potentially improving outcomes. This innovative approach could lead to more effective treatments with potentially fewer side effects compared to existing therapies.

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

In this trial, participants will receive different combinations of treatments. Research has shown that M9466, a powerful drug that blocks a protein involved in DNA repair, works well against tumors when combined with carboplatin, a chemotherapy drug. Some participants will receive M9466 with carboplatin, which studies have found to be more effective against tumors than carboplatin alone. Other participants will receive a combination of M9466, carboplatin, etoposide, and atezolizumab. Combining atezolizumab with carboplatin and etoposide has successfully treated advanced small cell lung cancer, supporting this treatment approach. Early results suggest these combinations can be safe and may improve outcomes for patients with advanced solid tumors. However, more research is needed to confirm these benefits. ^{1 2 5 6 7}

Who Is on the Research Team?

Medical Responsible

Principal Investigator

EMD Serono Research & Development Institute, Inc.

Are You a Good Fit for This Trial?

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

Other protocol defined inclusion criteria could apply

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

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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 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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06719973?term=AREA%5BInterventionSearch%5D(m9466)%20AND%20AREA%5BStudyType%5D(INTERVENTIONAL)&rank=2

Phase 1 Study of M9466 Combined With Carboplatin and ... The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamic, and preliminary clinical activity of M9466 in ...

2. researchgate.net researchgate.net/publication/390994116_Abstract_1171_M9466_HRS-1167_A_highly_potent_and_selective_PARP1_inhibitor_with_DNA_trapping_activity_monotherapy_antitumor_activity_and_synergistic_potential_with_DDR_inhibitors_and_chemotherapies

M9466 (HRS-1167): A highly potent and selective PARP1 ... Here, M9466 enhanced the antitumor efficacy of the ATR inhibitor tuvusertib and the chemotherapy carboplatin. Thus, M9466 has strong single ...

3. withpower.com withpower.com/trial/phase-1-solid-tumors-advanced-solid-tumors-2025-c6378

M9466 + Carboplatin for Solid Tumors · Info for Participants 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 ...

4. researchgate.net researchgate.net/publication/381968607_A_phase_1_study_of_HRS-1167_M9466_a_highly_selective_PARP1_inhibitor_in_patients_pts_with_advanced_solid_tumors

A phase 1 study of HRS-1167 (M9466), a highly selective ... Conclusions: HRS-1167 was well-tolerated and exhibited favorable safety and PK profiles in pts with advanced solid tumors, and demonstrated ...

5. synapse.patsnap.com synapse.patsnap.com/drug/392fd0ce0992424da5853f06fabd3909

HRS-1167 - Drug Targets, Indications, Patents An Open Label, Multicenter, Phase 1 Study to Evaluate the Safety, Tolerability, and Pharmacokinetic/Pharmacodynamic Profile of the PARP1 Inhibitor M9466 in ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06719973

NCT06719973 | Phase 1 Study of M9466 Combined With ... The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamic, and preliminary clinical activity of M9466 in ...

7. delta.larvol.com delta.larvol.com/Products/?ProductId=4f4e06c1-1a02-4aeb-9953-ca3dcaa58e3f

M9466 / Jiangsu Hengrui Pharma, EMD Serono A study for the treatment of metastatic prostate cancer with HRS-1167 tablets combined with abiraterone acetate tablets and prednisone.