Innovent Launches Phase II Trial of PD-1/IL-2 Bispecific IBI363 vs. Pembrolizumab in Melanoma; GSK Initiates Phase III DREAMM-10 Study of BCMA ADC Belantamab Mafodotin vs. Daratumumab in First-Line Multiple Myeloma

Jan 23, 2025 18:54 CST Updated 18:54

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Innovent Bio Initiates Phase II Clinical Trial of PD-1/IL-2 for Melanoma

Recently, the official website of the Drug Clinical Trial Registration and Information Disclosure Platform showed that Innovent Bio registered a Phase II clinical trial (CTR20250280) evaluating IBI363 monotherapy head-to-head against pembrolizumab (K drug) for the treatment of subjects with advanced melanoma.

This is a randomized, open-label, multi-center Phase II study aimed at evaluating the efficacy and safety of IBI363 monotherapy compared to pembrolizumab in subjects with unresectable locally advanced or metastatic mucosal and acral melanoma who have not previously received systemic treatment. The study plans to enroll 180 subjects.

The primary endpoint is progression-free survival (PFS) assessed by the Independent Radiological Review Committee (IRRC) according to the Response Evaluation Criteria in Solid Tumors (RECIST) V1.1. Secondary endpoints include PFS assessed by investigators, objective response rate (ORR) assessed by both IRRC and investigators, duration of response (DoR), disease control rate (DCR), time to response (TTR), overall survival (OS), etc.

IBI363 is a globally pioneering PD-1/IL-2 bispecific fusion protein independently developed by Innovent Bio. It possesses two functions: blocking the PD-1/PD-L1 pathway and activating the IL-2 pathway. The IL-2 arm of IBI363 has been specially engineered to retain its affinity for IL-2 Rα while reducing its binding ability to IL-2Rβ and IL-2Rγ, thereby decreasing toxicity. Meanwhile, the PD-1 binding arm can both block PD-1 and enable selective delivery of IL-2.

In September 2024, IBI363 was granted Fast Track designation by the U.S. FDA for the proposed indication of locally advanced or metastatic melanoma (excluding uveal melanoma) that has progressed after receiving at least one prior line of systemic treatment containing a PD-1/L1 checkpoint inhibitor.

GSK Launches BCMA ADC Head-to-Head Daratumumab Phase III Clinical Trial

Recently, GSK registered a Phase III DREAMM-10 study on the Drug Clinical Trial Registration and Information Disclosure Platform, investigating Belantamab mafodotin (Marabalantamab) in combination with lenalidomide and dexamethasone (BRd) versus daratumumab in combination with lenalidomide and dexamethasone (DRd) as first-line treatment for multiple myeloma.

DREAMM-10 is a randomized, parallel-group, open-label international multicenter Phase III clinical trial designed to evaluate the efficacy and safety of BRd versus DRd in newly diagnosed multiple myeloma (TI-NDMM) participants who are ineligible for autologous stem cell transplantation. A total of 165 institutions globally are participating, with plans to enroll 80 participants in China and 520 participants internationally. The primary endpoints are progression-free survival (PFS) and MRD-negative status.

Belantamab mafodotin is a BCMA-targeted antibody-drug conjugate (ADC). In August 2020, based on the pivotal Phase II DREAMM-2 clinical trial results, the drug received accelerated approval from the FDA and conditional approval from the EMA for marketing. It was approved as a monotherapy for the treatment of adult patients with relapsed/refractory multiple myeloma, becoming the world's first approved BCMA ADC.

However, due to the failure of the Phase III DREAMM-3 study to meet its primary endpoint of PFS, GSK voluntarily withdrew the U.S. marketing application for Belantamab mafodotin in November 2022. In April 2024, the EU also withdrew the marketing authorization for Belantamab mafodotin.

Although the initial market launch was not smooth, research shows that Belantamab mafodotin can still benefit some patients with multiple myeloma. In November 2024, GSK announced that the interim analysis of the Phase III DREAMM-7 study, which compares Belantamab mafodotin in combination with bortezomib and dexamethasone (BorDex) head-to-head against daratumumab combined with BorDex as a second-line treatment for relapsed or refractory multiple myeloma, achieved positive results, meeting the key secondary endpoint of overall survival (OS).

GSK has successively submitted the marketing application for Belantamab mafodotin as a second-line treatment for multiple myeloma to regulatory agencies such as NMPA, FDA, and EMA.

Editor: Wanwan