Minghui Pharmaceutical has successfully dosed the first patient in a Phase II clinical trial investigating a novel combination therapy for advanced non-small cell lung cancer (NSCLC). The trial will evaluate the safety and efficacy of MHB039A, a PD-1xVEGF bispecific antibody, together with MHB036C, a TROP-2-directed antibody-drug conjugate (ADC).
The Shanghai-based biopharmaceutical company announced this milestone on May 20, 2025, marking a significant step in their oncology development program. This combination approach represents an emerging strategy in cancer treatment that pairs targeted immunotherapy with precision cytotoxic delivery.
Novel Bispecific Antibody Shows Promising Early Results
MHB039A is designed to simultaneously target two critical cancer pathways: PD-1, which helps cancer cells evade immune detection, and VEGF, which promotes tumor blood vessel formation. According to Minghui, the bispecific antibody demonstrated full blocking activities against both targets with superior PD-1 activity compared to competitor antibodies.
In a completed Phase I dose-escalation study, MHB039A was well-tolerated at doses up to 30 mg/kg, with no dose-limiting toxicities observed and the maximum tolerated dose not reached. The safety profile aligned with previously reported PD-1xVEGF bispecifics.
Importantly, robust PD-1 receptor occupancy and VEGF biomarker responses were observed across all dose levels. Early efficacy signals were particularly encouraging in NSCLC patients who had previously progressed after PD-1 inhibitor and chemotherapy treatment—a population with significant unmet medical needs.
Proprietary ADC Platform Yields Promising TROP-2 Candidate
The second component of the combination, MHB036C, is a novel antibody-drug conjugate targeting TROP-2, a cell surface glycoprotein frequently overexpressed in many epithelial cancers. The ADC was developed using Minghui's proprietary SuperTopoi™ platform.
In ongoing Phase 1/2 studies involving 138 patients with advanced or metastatic solid tumors, MHB036C has demonstrated a favorable safety profile. Notably, the treatment has shown no major hematologic adverse events or interstitial lung disease (ILD)—toxicities that have hampered other ADCs in development.
The company reports promising anti-tumor activity in heavily pre-treated NSCLC and breast cancer patients, though specific response rates have not yet been disclosed.
Strategic Combination Approach
"We are excited to initiate this Phase II trial investigating the combination therapy with MHB039A and MHB036C in advanced NSCLC," said Guoqing Cao, Ph.D., Chief Executive Officer of Minghui Pharmaceutical. "Emerging clinical data increasingly support the potential of combining ADCs with immuno-oncology agents to achieve more robust and durable anti-tumor responses across multiple solid tumors."
Dr. Cao emphasized the company's belief that such combinations will play a pivotal role in reshaping standard-of-care treatment paradigms. The PD-1xVEGF bispecific antibody is positioned as a promising new backbone for immuno-oncology-based combination therapies.
The strategic focus on developing ADCs and PD-1xVEGF bispecific combination therapies establishes a foundation for potentially extending this approach to other solid tumors, including breast cancer, according to the company.
Addressing Significant Unmet Needs in NSCLC
Non-small cell lung cancer remains one of the most common and deadly forms of cancer worldwide. Despite advances in targeted therapies and immunotherapies, many patients develop resistance to treatment or experience disease progression.
The combination approach being tested by Minghui aims to address these challenges by simultaneously targeting multiple cancer pathways. By blocking PD-1 and VEGF while delivering a potent cytotoxic payload to TROP-2-expressing cancer cells, the company hopes to overcome resistance mechanisms and improve outcomes for patients with advanced disease.
Looking Forward
While the Phase II trial is just beginning, the combination of MHB039A and MHB036C represents an innovative approach in the evolving landscape of cancer therapeutics. The study will provide important insights into whether dual targeting of immune checkpoints and angiogenesis, combined with targeted cytotoxic delivery, can improve outcomes for patients with advanced NSCLC.
Minghui Pharmaceutical has not disclosed the expected timeline for preliminary or final results from this trial, nor specific details about the trial design, patient enrollment targets, or primary endpoints. However, the company's approach aligns with the broader industry trend toward rational combinations of complementary therapeutic modalities to improve efficacy while managing toxicity profiles.
