Cullinan Therapeutics to Present Initial CLN-619 Data and Updated Monotherapy Results at ASCO 2024

Cullinan Therapeutics has revealed promising preliminary data from its Phase 1 clinical trial of CLN-619 in combination with the checkpoint inhibitor pembrolizumab. The findings show that CLN-619, an innovative antibody targeting MICA/B, can elicit objective responses in patients with tumors that typically do not respond to pembrolizumab, such as non-small cell lung cancer (NSCLC) with oncogenic mutations.

The study results will be presented at the 2024 ASCO Annual Meeting in the "Developmental Therapeutics—Immunotherapy" session. The data highlight the potential of CLN-619 to provide clinical benefits across multiple tumor types. Among the 22 patients treated with the combination of CLN-619 and pembrolizumab, 18 were assessable for response under RECIST criteria. Three patients showed confirmed partial responses at doses of 3 mg/kg or higher.

Specifically, responses were observed in patients with NSCLC who had mutations in EGFR and ALK, as well as those with gastric cancer overexpressing HER2. These patients typically do not benefit from checkpoint inhibitor treatment. In the NSCLC group, eight of eleven patients were RECIST-evaluable, with six having oncogenic mutations. Three of these six patients experienced significant clinical benefits, including two partial responses and one instance of stable disease lasting over 18 weeks.

The monotherapy cohort also showed promising results. Among the 42 patients treated with CLN-619 alone, 29 received doses of 1 mg/kg or higher, and the clinical benefit rate was 41.4%. The monotherapy group included diverse tumor types, with one patient achieving a complete response and two achieving partial responses. Stable disease for 18 weeks or longer was observed in nine patients, spanning various cancers, suggesting wide-ranging efficacy.

In terms of safety, CLN-619 was well tolerated both as a monotherapy and in combination with pembrolizumab. Most treatment-related adverse events (TRAEs) were mild (grade 1 or 2), with the most common being infusion-related reactions and fatigue. Only one patient in each cohort discontinued treatment due to TRAEs, and there were no treatment-related deaths. The only grade 3 or higher TRAE occurring in more than 5% of patients was an increase in AST in the monotherapy group.

These results have prompted Cullinan to expand the trial to include additional monotherapy and combination cohorts, particularly focusing on NSCLC. The company aims to explore the potential of CLN-619 further in cervical and endometrial cancers and plans to study it in Phase 1 trials for relapsed/refractory multiple myeloma.

CLN-619 works by restoring the expression of MICA/B on tumor cells, which helps reinvigorate the immune system's NKG2D-mediated response. This mechanism, combined with inducing antibody-dependent cellular toxicity (ADCC) and phagocytosis (ADCP), contributes to its anti-tumor activity.

Dr. Jeffrey Jones, Chief Medical Officer of Cullinan Therapeutics, highlighted the significance of these findings, particularly for patients with NSCLC who have relapsed after tyrosine kinase inhibitors and typically do not respond to checkpoint inhibitors. Dr. Alexander Spira emphasized the unmet need for innovative therapies that can be combined with established checkpoint inhibitors, noting the potential benefits of CLN-619 in this context.

Cullinan Therapeutics plans to continue its research to confirm these findings and potentially bring CLN-619 to market, aiming to address significant gaps in cancer treatment. The company remains focused on developing therapies that can harness the immune system to combat various malignancies, offering new hope to patients with challenging cancer types.