#None #Lung Cancer #Multitude Therapeutics #AMT-116

Multitude Therapeutics Shares Encouraging Phase I/II Results for AMT-116

At the recent European Society for Medical Oncology (ESMO) Annual Meeting 2025 held in Berlin on October 17, Multitude Therapeutics, Inc. presented promising interim results from its ongoing Phase I/II study evaluating AMT-116, an innovative CD44v9-directed antibody-drug conjugate (ADC). This ADC aims to treat heavily pretreated EGFR wild-type non-small cell lung cancer (NSCLC) and other advanced solid tumors.

AMT-116 stands out as a potential first-in-class therapeutic, integrating a CD44v9-targeting mechanism with a topoisomerase I inhibitor. The early data indicate that AMT-116 successfully maintains a favorable safety profile while showcasing encouraging efficacy in a diverse patient population. This pivotal trial commenced across several regions, including Australia, the United States, and China, involving multiple centers to assess its maximum tolerated dose and effective treatment potential.

As of July 2025, findings for 164 patients had been reported, focusing on those whose primary tumors consist of various malignancies, including NSCLC, nasopharyngeal carcinoma (NPC), anal carcinoma, and salivary gland cancer. Among patients with heavily pretreated EGFR wild-type NSCLC, a significant overall response rate (ORR) of 40% was observed. Notably, at higher dosage levels (greater than 3 mg/kg), the disease control rate (DCR) reached an impressive 93%. In a smaller cohort of patients treated with a 5.0 mg/kg dosage, the ORR increased significantly to 80%, indicating robust antitumor activity.

Additionally, the efficacy of AMT-116 transcended beyond NSCLC, demonstrating preliminary antitumor effects in patients with NPC (50% ORR), anal carcinoma (60% ORR), and salivary gland cancer (33% ORR) at similar dosage levels. These findings underscore an encouraging trend, as AMT-116 maintained efficacy irrespective of CD44v9 expression levels.

The safety profile of AMT-116 has also been reassuring, aligning with that of other topoisomerase I inhibitor-based ADCs, where manageable hematologic toxicities emerged as the primary treatment-related adverse events. The incidence of mucosal and skin toxicities remained infrequent and low-grade, suggesting that the treatment is tolerable for patients.

Dr. Shu-Hui Liu, co-founder and Chief Scientific Officer of Multitude Therapeutics, expressed his enthusiasm regarding the early results, stating, "This early data demonstrates impressive and sustained efficacy, particularly in unselected heavily pretreated EGFR wild-type NSCLC patients and other advanced solid tumors. Our observations correlate well with prior preclinical studies showcasing broad tumor expression. Moreover, the minimized mucosal and skin toxicities reflect our advanced linker-payload platform's goal to alleviate on-target toxicities."

Given these optimistic developments, the study plans to expand cohorts receiving the clinically efficacious doses of 4 mg/kg and 5 mg/kg in select tumor types to fully explore AMT-116's therapeutic potential, aiming to improve patient outcomes in NSCLC and other challenging cancer types.

The AMT-116 ADC employs a proprietary antibody known for strong CD44v9 binding capability, combined with a hydrolysable linker and a derivative of belotecan, a clinically validated topoisomerase-1 inhibitor. With CD44v9 being a protein of considerable presence in solid tumors yet with limited expression in normal tissue, AMT-116 aspires to achieve a potent therapeutic effect with minimized side effects.

For those interested in the ongoing trials, more details can be found in clinicaltrials.gov under the identifiers NCT05725291 and NCT06782334 for the ongoing studies in Australia, the US, and China.

Through platforms like MabArray™ and T1000-exatecan, Multitude Therapeutics aims to pioneer the development of ADCs that will address pressing needs in oncology by providing more effective and safer treatment options. As the company further advances in its research, AMT-116 holds the promise of delivering significant breakthroughs in cancer therapy.