CLN-619 / Cullinan Therap - LARVOL DELTA

A Study of CLN-619 Alone and in Combination With Pembrolizumab in Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=410 | Recruiting | Sponsor: Cullinan Oncology Inc. | Trial completion date: Mar 2026 ➔ Jun 2026 | Trial primary completion date: Sep 2025 ➔ Mar 2026

Combination therapy • Metastases • Trial completion date • Trial primary completion date • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • ALK • EGFR

A Study of CLN-619 Alone and in Combination With Pembrolizumab in Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=410 | Recruiting | Sponsor: Cullinan Oncology, LLC | N=148 ➔ 410

Combination therapy • Enrollment change • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • ALK • EGFR

CLN-619, a clinical stage MICA/B-specific hIgG1 monoclonal antibody, engages multiple immune effector cells to promote anti-tumor activity (AACR 2024) - P1 | "In the context of macrophages, we measured the ability of CLN-619 to mediate ADCP against MICA/B-expressing target cells. These data highlight the potential of CLN-619 to engage multiple immune cell types within the TME, which may lead to greater and broader efficacy compared to IO therapies targeting a single immune cell type."

Clinical • Hematological Malignancies • Oncology • CD8 • MICA • MICB • NKG2D

CLN-619-001: A Study of CLN-619 Alone and in Combination With Pembrolizumab in Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=440 | Active, not recruiting | Sponsor: Cullinan Therapeutics Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Cervical Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • ALK • EGFR

A Study of CLN-619 (Anti-MICA/MICB Antibody) in Patients With Relapsed and Refractory Multiple Myeloma (clinicaltrials.gov) - P1 | N=30 | Active, not recruiting | Sponsor: Cullinan Therapeutics Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Hematological Malignancies • Multiple Myeloma • Oncology

CLN-619 (Anti-MICA/MICB monoclonal antibody) (GlobeNewswire) - "Cullinan will continue enrolling to go/no-go decisions the ongoing expansion cohorts in patients with NSCLC and the ongoing Phase 1 study in patients with relapsed/refractory multiple myeloma."

Trial status • Multiple Myeloma • Non Small Cell Lung Cancer

CLN-619, a MICA/B monoclonal antibody that promotes innate immune cell-mediated antitumor activity. (PubMed, J Immunother Cancer) - "CLN-619 inhibited the shedding of MICA/B to effectively restore cytotoxic signaling pathways in immune cells. Potent antitumor activity of CLN-619 as a monotherapy was observed in several preclinical models. Activity of CLN-619 required a functional Fcγ1 domain, suggesting the requirement of simultaneous engagement of NKG2D and cluster of differentiation 16A (CD16A) on immune cells for optimal cytotoxicity. The preclinical data reported here support the assessment of CLN-619 in patients with cancer."

Journal • Oncology • CD1a • FCGR3A • MICA • MICB • NKG2D

Cullinan Therapeutics Provides Corporate Update and Reports Fourth Quarter and Full Year 2024 Financial Results (GlobeNewswire) - "CLN-619 (Anti-MICA/MICB monoclonal antibody): The Company continues enrollment of disease-specific expansion cohorts of its Phase 1 study. Cullinan remains on track to report initial data for endometrial and cervical cancers in the second quarter of 2025; Enrollment continues in the ongoing Phase 1 study of CLN-619 in patients with relapsed/refractory multiple myeloma."

P1 data • Trial status • Cervical Cancer • Endometrial Cancer • Multiple Myeloma

Pharmacodynamic activities of the anti-MICA/B monoclonal antibody CLN-619, evaluated as a monotherapy, support the proposed mechanisms of action and correlate with response (SITC 2024) - P1 | "CLN-619 as a monotherapy and in combination with pembrolizumab demonstrated a favorable safety profile and objective RECIST responses in patients with multiple solid tumor types in a Phase I clinical trial (NCT05117476).1 Here we report pharmacodynamic activities associated with CLN-619 monotherapy. Furthermore, these changes appear associated with response. The results emphasize the potential of CLN-619 as a novel immunotherapy for the treatment of a range of solid tumors."

IO biomarker • Monotherapy • PK/PD data • Oncology • Solid Tumor • CD4 • FOXP3 • MICA • MICB • NCAM1 • NKG2D

Dr Moreno on the Pharmacodynamics of CLN-619 in Advanced Solid Tumors (OncLive) - P1 | N=410 | NCT05117476 | Sponsor: Cullinan Therapeutics Inc. | "Peripheral blood analyses showed an increase in CD56-positive and natural killer G2D (NKG2D)–positive cells, Moreno says, adding that T-cell counts were also elevated. He notes that these findings help support the proposed mechanism of action for CLN-619....In tumor biopsies, post-treatment samples revealed a greater infiltration of NK cells in patients who responded to therapy compared with non-responders...Notably, these responders demonstrated higher levels of CD56-positive and NKG2D-positive cells within the tumor after treatment vs baseline. Additionally, investigators observed a decrease in regulatory T cells in the tumor microenvironment following CLN-619 treatment."

P1 data • Oncology • Solid Tumor

Cullinan Therapeutics Provides Corporate Update and Reports Third Quarter 2024 Financial Results (GlobeNewswire) - "CLN-619 on-track for initial expansion cohort data in endometrial and cervical cancers in Q2 2025; Zipalertinib pivotal Phase 2b study enrollment completed ahead of schedule; results expected mid-year 2025."

P1 data • P2b data • Cervical Cancer • Endometrial Cancer • Non Small Cell Lung Cancer

Cullinan Therapeutics Provides Corporate Update and Reports Second Quarter 2024 Financial Results (GlobeNewswire) - "Oncology: (i) CLN-619 (Anti-MICA/MICB monoclonal antibody):...Cullinan remains on track to report initial data from disease-specific dose expansion cohorts in endometrial and cervical cancers in the first half of 2025....(ii) Zipalertinib (EGFR ex20ins inhibitor):...An update to these initial REZILIENT1 results in patients with EGFR ex20ins NSCLC who have progressed after both prior chemotherapy and amivantamab will be presented in a mini oral presentation at the European Society for Medical Oncology (ESMO) meeting in September. Cullinan expects to complete enrollment in the pivotal Phase 2b portion of REZILIENT1 by year-end 2024."

Enrollment status • P1 data • P1/2 data • Cervical Cancer • Endometrial Cancer • Non Small Cell Lung Cancer

A Study of CLN-619 (Anti-MICA/MICB Antibody) in Patients With Relapsed and Refractory Multiple Myeloma (clinicaltrials.gov) - P1 | N=30 | Recruiting | Sponsor: Cullinan Therapeutics Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Hematological Malignancies • Multiple Myeloma • Oncology

Cln-619 (anti-MICA/B antibody) alone and in combination with pembrolizumab (P) for advanced solid tumors: Updated results of a Ph1 study. (ASCO 2024) - P1 | "CLN-619 + P was well tolerated at doses ranging from 1 to 10 mg/kg. Objective responses were observed, including in tumor types typically unresponsive to P. Longer term follow-up for CLN-619 monotherapy confirms favorable safety and durable clinical benefit with extended treatment, including objective responses in multiple tumor types and pts progressing after CPI. Based on these findings, expansion cohorts will be opened in endometrial cancer and NSCLC."

Combination therapy • Metastases • Adenoid Cystic Carcinoma • Cervical Cancer • Constipation • Endometrial Cancer • Fatigue • Gastric Cancer • Gastroenterology • Gastrointestinal Cancer • Gastrointestinal Disorder • Hormone Receptor Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pain • Sarcoma • Solid Tumor • Uterine Cancer • NKG2D • STK11

Cullinan Therapeutics to Present First Data for CLN-619, a Novel Anti-MICA/B Antibody, in Combination with a Checkpoint Inhibitor and Updated Monotherapy Data at ASCO 2024 (Morningstar.com) - "'There remains significant unmet need for patients with NSCLC with oncogenic mutations relapsing after TKIs, so we see a potential benefit in novel therapies that can be easily combined with established CPIs,' said Alexander Spira, MD, PhD...'Combining CLN-619 with pembrolizumab engages multiple immune effector cells, including innate cells by CLN-619 and T cells by pembrolizumab. The safety profile of CLN-619 along with the biologic rationale for combination with CPI make this a potentially synergistic approach.'"

Checkpoint inhibition • Media quote

Cullinan Therapeutics to Present First Data for CLN-619, a Novel Anti-MICA/B Antibody, in Combination with a Checkpoint Inhibitor and Updated Monotherapy Data at ASCO 2024 (GlobeNewswire) - P1 | N=410 | NCT05117476 | Sponsor: Cullinan Therapeutics Inc. | "Cullinan Therapeutics...announced first clinical data from its Phase 1 dose escalation cohort of CLN-619 in combination with checkpoint inhibitor (CPI) pembrolizumab and updated results from the monotherapy dose escalation cohort in patients with advanced solid tumors...Of 22 patients treated with CLN-619 in combination with pembrolizumab, 18 were RECIST-evaluable for response; Confirmed partial responses (PR) were observed in 3 patients treated with CLN-619 at doses ≥3mg/kg in combination with pembrolizumab; Responses were observed in patients with tumor types not typically responsive to CPI treatment...8 of the 11 patients with NSCLC were RECIST-evaluable; of these, 6 had oncogenic mutations....The clinical benefit rate (CBR) was 41.4% (1 complete response (CR), 2 PR, 9 SD ≥18 weeks)."

P1 data • Oncology • Solid Tumor

A Study of CLN-619 (Anti-MICA/MICB Antibody) in Patients With Relapsed and Refractory Multiple Myeloma (clinicaltrials.gov) - P1 | N=30 | Not yet recruiting | Sponsor: Cullinan Therapeutics Inc.

New P1 trial • Hematological Malignancies • Multiple Myeloma • Oncology

Cullinan Therapeutics to Present Clinical Data from Phase 1 Study Evaluating Novel Anti-MICA/B Antibody, CLN-619, as Monotherapy and in Combination with a Checkpoint Inhibitor in Patients with Advanced Solid Tumors at ASCO 2024 (GlobeNewswire) - "Cullinan Therapeutics, Inc...today announced that clinical data from its Phase 1 trial of CLN-619 in patients with advanced solid tumors will be presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting taking place in Chicago from May 31-June 4, 2024. The data will include first results from the dose escalation cohort of CLN-619 in combination with checkpoint inhibitor pembrolizumab and updated results from the monotherapy dose escalation cohort in patients with advanced solid tumors."

P1 data • Solid Tumor

Cullinan Oncology Provides Corporate Update and Reports Fourth Quarter and Full Year 2023 Financial Results (GlobeNewswire) - "CLN-619: Cullinan remains on track to report initial data from the combination dose escalation module as well as an update on the monotherapy dose escalation module at a medical conference in the second quarter of 2024; Cullinan also remains on track to report initial data from disease specific dose expansion cohorts in the first half of 2025."

P1 data • Cervical Cancer • Gynecologic Cancers • Hematological Malignancies • Oncology • Solid Tumor

Cullinan Oncology Announces U.S. FDA Clearance of Investigational New Drug Application for Novel MICA/B Antibody, CLN-619, for Relapsed/Refractory Multiple Myeloma (GlobeNewswire) - "Cullinan Oncology, Inc...announced the U.S. Food and Drug Administration (FDA) has cleared its Investigational New Drug (IND) application for CLN-619 in relapsed/refractory multiple myeloma....The company will commence a Phase 1 dose-escalation and dose-expansion trial of CLN-619.... This Phase 1 trial will assess CLN-619 in patients with multiple myeloma, and, given the safety profile shown to date for CLN-619, we believe there is an opportunity to combine the monoclonal antibody with multiple standard therapies."

IND • New P1 trial • Hematological Malignancies • Multiple Myeloma • Oncology

Cullinan Oncology Provides Corporate Update and Reports Third Quarter 2023 Financial Results (GlobeNewswire) - "Upcoming Milestones - CLN-619: Cullinan expects to report initial data from the combination dose escalation module as well as an update on the monotherapy dose escalation module at a medical conference in the second quarter of 2024. Cullinan expects to report initial data from disease specific dose expansion cohorts in the first half of 2025. Zipalertinib: Cullinan expects completion of enrollment in the pivotal Phase 2b portion of the REZILIENT1 study by year-end 2024. CLN-049: Cullinan expects to provide a clinical data update in the second half of 2024. CLN-418: Cullinan expects to provide a clinical data update in the second half of 2024."

Clinical data • P1 data • Trial status • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Characterization of the pharmacodynamic activity of CLN-619, an anti-MICA/B monoclonal antibody, in patients from an ongoing Phase 1 trial (SITC 2023) - P1 | "CLN-619 is currently being investigated in a Phase I clinical trial in patients with advanced solid tumors as a monotherapy and in combination with pembrolizumab (NCT05117476). Characterization of gene expression profiles and mutational analysis of tumor biopsies is ongoing. Conclusions Pharmacodynamic data presented here are consistent with the proposed mechanisms of action of CLN-619, demonstrate stabilization of MICA/B expression in tumors, and support the potential of CLN-619 as a novel immunotherapy for the treatment of a range of solid tumors."

Clinical • IO biomarker • P1 data • PK/PD data • Tumor mutational burden • Oncology • Solid Tumor • CD8 • MICA • MICB • NKG2D • TMB

Cullinan Oncology to Present Data Demonstrating Progress Across Its Broad Immunotherapy-Pipeline at SITC 2023 (GlobeNewswire) - P1 | N=410 | NCT05117476 | Sponsor: Cullinan Oncology, LLC | "Initial clinical biomarker data demonstrates that CLN-619 increases MICA expression on the tumor cell surface, consistent with previously reported preclinical data and supporting the proposed mechanism of action. Data from patients with available biopsy data demonstrate clinical benefit, including objective response, in patients with tumors with characteristics not typically responsive to checkpoint inhibitor therapy. Specifically, tumors from two patients with endometrial cancer and previously reported confirmed partial responses were microsatellite stable (MSS), had low tumor mutational burden, and low neoantigen presentation index."

P1 data • Endometrial Cancer • Gynecologic Cancers • Microsatellite Instability • Oncology • Solid Tumor

Cullinan Oncology Provides Corporate Update and Reports Second Quarter 2023 Financial Results (GlobeNewswire) - "CLN-619: Cullinan intends to present initial data from the combination dose escalation arm of the study at a medical meeting in the future; CLN-418: Enrollment continued in the ongoing Phase 1 dose escalation study in patients with advanced solid tumors. Initial clinical data are expected in 2024; CLN-617: Cullinan received FDA clearance of its IND application for CLN-617 in March and anticipates initiating a Phase 1 clinical study in the second half of 2023."

P1 data • Trial initiation date • Oncology • Solid Tumor

A phase 1 dose-escalation study to investigate the safety, efficacy, pharmacokinetics, and pharmacodynamic activity of cln-619 (Anti-MICA/B antibody) alone and in combination with pembrolizumab in patients with advanced solid tumors. (ASCO 2023) - P1 | "CLN-619 therapy was well tolerated at doses ranging from 0.1 to 10 mg/kg and demonstrated monotherapy clinical activity, including objective response in a patient progressing after PD-1. Updated data from the dose-escalation portion of the trial will be presented. Clinical trial information: NCT05117476."

Clinical • Combination therapy • Metastases • P1 data • PK/PD data • Cervical Cancer • Oncology • Pain • Salivary Gland Cancer • Solid Tumor • NKG2D