A Study of MHB088C Injection Versus Treatment of Physician's Choice in Subjects With Relapsed Small Cell Lung Cancer

A Phase 3, Multicenter, Randomized, Open-label Study of MHB088C for Injection Versus Treatment of Physician's Choice (TPC) in Comparing the Efficacy and Safety in Subjects With Relapsed Small Cell Lung Cancer (SCLC)

This study was designed to compare the efficacy and safety of MHB088C for Injection with treatment of physician's choice (TPC) in participants with relapsed small cell lung cancer (SCLC).

Study Overview

• Status: Recruiting
• Conditions: Small Cell Lung Cancer Extensive Stage
• Intervention / Treatment: Drug: MHB088C for Injection; Drug: Topotecan; Drug: Irinotecan; Drug: Paclitaxel

Detailed Description

The primary objective of this study is to assess whether treatment with MHB088C for Injection improves prolongs overall survival (OS) compared with treatment of physician's choice among participants with relapsed SCLC.

The secondary objectives of the study are to further evaluate the efficacy/safety of MHB088C for Injection, immunogenicity of MHB088C, and characterize the pharmacokinetics of MHB088C.

• Study Type: Interventional
• Enrollment (Estimated): 450
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: VP of R&D; Phone Number: 86 0571-86963293; Email: jwshi@minghuipharma.com

Study Locations

• China
  • Shanghai, China
    • Recruiting
    • Shanghai East Hospital
    • Contact: Caicun Zhou; Phone Number: 13301825532; Email: caicunzhoudr@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Participants must meet all the following criteria to be eligible for randomization into the study:

1. Voluntarily consent to participate in this study and sign the informed consent form.
2. Adults ≥18 years, regardless of gender.
3. ECOG performance status score of 0-1.
4. Estimated survival time of more than 3 months.
5. Capable of understanding trial requirements, willing and able to comply with trial and follow-up procedures.
6. Has histologically or cytologically documented small cell lung cancer (SCLC).
7. Extensive-stage SCLC with disease progression after at least two cycles of platinum-based and PD-1/L1 systemic therapy, with no more than two prior lines of therapy. Prior PD-1/L1 systemic therapy was allowed to use with or without platinum-based regimens.
8. Agrees to provide pre-treatment tumor tissue samples for retrospective analysis of B7-H3 expression and other biomarkers.
9. Has at least 1 measurable lesion according to RECIST v1.1 as assessed by the investigator.
10. Sufficient bone marrow and organ function.

Exclusion Criteria:

Participants who meet any of the following criteria will be disqualified from entering the study:

1. Diagnosis of other primary malignancies within 5 years prior to signing the informed consent form.
2. Prior pathological diagnosis of combined SCLC, or any transformed non-small cell lung cancer or transformed SCLC.
3. Receipt of chemotherapy within 4 weeks prior to the first administration of study drug, or receipt of radiotherapy, biologics, endocrine therapy, immunotherapy, or other anti-tumor therapy within 4 weeks prior to the first dose.
4. Previous or ongoing treatment with topoisomerase I inhibitors, including antibody-drug conjugates (ADCs) containing topoisomerase I inhibitor payloads.
5. Brain metastases (unless asymptomatic and stable for more than 4 weeks prior to randomization); presence of leptomeningeal metastases or brainstem metastases; spinal cord compression (identified via imaging, regardless of symptoms).
6. Bone marrow metastasis.
7. Prior B7-H3-targeted therapy.
8. Has uncontrolled or significant cardiovascular disease.
9. Moderate-to-severe pulmonary disease significantly impairing lung function, including idiopathic pulmonary fibrosis, autoimmune/connective tissue disorders with lung involvement, or prior pneumonectomy.
10. Has history of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required corticosteroids, current ILD/pneumonitis, or suspected ILD/pneumonitis that cannot be ruled out by imaging at Screening.
11. Moderate or severe pulmonary diseases severely affecting lung function.
12. Active tuberculosis, autoimmune diseases not in clinical remission, other acquired or congenital immunodeficiency diseases, or history of allogeneic stem cell, bone marrow, or organ transplantation.
13. Serious infections within 4 weeks before the first dose, including but not limited to those requiring systemic antibiotic therapy, bacteremia, or severe pneumonia.
14. Clinically uncontrolled third-space effusion requiring intervention, including pleural or peritoneal effusions.
15. Known hypersensitivity to investigational product components, analogues, or control drugs (e.g., topotecan, irinotecan, paclitaxel).
16. Pregnant or lactating women, or women/men intending to conceive.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MHB088C for Injection; Participants randomized to receive 2 mg/kg MHB088C monotherapy on Day 1 and Day 15 of each 28-day cycle until unacceptable toxicity, progressive disease (PD), or withdrawal of consent as specified in the protocol.	Drug: MHB088C for Injection; 2 mg/kg intravenous dose on Day 1 and Day 15 of each 28-day cycle
Active Comparator: Treatment of Physician's Chioce (TPC); Participants randomized to receive topotecan, irinotecan, or paclitaxel, as per investigator's choice and per approved label (indicated dose and frequency), until a treatment discontinuation criterion is met as specified in the protocol.	Drug: Topotecan; 1.25 mg/m^2 intravenous dose on Day 1 to Day 5 of each 21-day cycle; Drug: Irinotecan; 65 mg/m^2 intravenous dose on Day 1 and Day 8 of each 21-day cycle; Drug: Paclitaxel; 135 mg/m^2 intravenous dose on Day 1 of each 21-day cycle

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Overall Survival	From the date of randomization to the date of death due to any cause, up to approximately 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Objective Response Rate Assessed by Investigator	Confirmed objective response rate (ORR) is defined as the sum of the complete response (CR) rate and partial response (PR) rate based on investigator by Response Evaluation Criteria In Solid Tumors (RECIST) v1.1.	Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 5 years
Progression-free Survival As Assessed by Investigator	PFS is defined as the time interval from the date of randomization to the date of disease progression as per investigator assessment or death due to any cause.	Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 5 years
Duration of Response As Assessed by Investigator	Duration of response (DoR) is defined as the time from the date of the first documentation of objective response (complete response [CR] or partial response [PR]) to the date of the first documentation of progressive disease (PD) or death. The DoR will be calculated for responding participants (PR or CR) only.	From the date of first documentation of confirmed response (CR or PR) to the first documentation of objective progression or to death due to any cause, whichever occurs first, up to approximately 5 years
Disease Control Rate As Assessed by Investigator	Disease control rate is defined as the proportion of participants who have achieved a best overall response of confirmed CR, confirmed PR, or SD (or non-CR/non-PD) by investigator assessment per RECIST v1.1.	Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 5 years
Incidence and severity of adverse events (AEs), serious adverse events (SAEs), AEs leading to treatment interruption, and AEs leading to treatment discontinuation.	Assessed based on NCI CTCAE v5.0	Baseline up to 5 years
Pharmacokinetic Parameter Maximum Concentration for MHB088C, Total Anti-B7-H3 Antibody, and MH30010008	Maximum concentration (Cmax) will be assessed using non-compartmental methods in participants randomized to the MHB088C group.	Day 1 and 15 of Cycle 1 before infusion (BI), end of infusion (EOI), and 5 hours after completion of infusion; Day 1 of Cycle 2 to Cycle 5, BI and EOI; Day 1 of Cycle 6 and every 3 cycles thereafter up to 5 years and EOT visit, BI (each cycle is 28 days)
Pharmacokinetic Parameter Time to Maximum Concentration for MHB088C, Total Anti-B7-H3 Antibody, and MH30010008	Pharmacokinetic Parameter Time to Maximum Concentration for MHB088C, Total Anti-B7-H3 Antibody, and MH30010008.	Day 1 and 15 of Cycle 1 before infusion (BI), end of infusion (EOI), and 5 hours after completion of infusion; Day 1 of Cycle 2 to Cycle 5, BI and EOI; Day 1 of Cycle 6 and every 3 cycles thereafter up to 5 years and EOT visit, BI (each cycle is 28 days)

Collaborators and Investigators

• Sponsor: Qilu Pharmaceutical Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): June 4, 2025
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): April 1, 2028

Study Registration Dates

• First Submitted: April 18, 2025
• First Submitted That Met QC Criteria: April 24, 2025
• First Posted (Actual): May 1, 2025

Study Record Updates

• Last Update Posted (Actual): June 18, 2025
• Last Update Submitted That Met QC Criteria: June 15, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: Small Cell Lung Cancer; B7H3; MHB088C
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Small Cell Lung Carcinoma; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Topoisomerase I Inhibitors; Topoisomerase Inhibitors; Antineoplastic Agents, Phytogenic; Irinotecan; Paclitaxel; Topotecan
• Other Study ID Numbers: MHB088C-P-301

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No