1145MO - CVM-005: Phase IIa study of CVM-1118, a novel oral anti-vasculogenic mimicry (VM) agent, in advanced neuroendocrine tumors (NET) after progression on prior therapy

Background

NETs are characterized by high vascularity, a viable target for anti-VM activity. CVM-1118 is a potent anti-tumor new chemical entity with multiple mechanisms of action, including disruption of VM networks, induction of apoptosis and cell cycle arrest. Earlier studies showed moderate efficacy and favorable safety profile at 200 to 300 mg BID of oral CVM-1118. We hereby present the results for the Phase IIa study in NET.

Methods

CVM-005 was a prospective, single-arm, phase IIa study enrolling patients (pts) with advanced NETs of low to intermediate grade (G1–G2) lung, gastrointestinal or pancreatic origin that were refractory to standard of care therapy and progressed within 6 months prior to screening. Pts received oral CVM-1118 at 200 to 300 mg BID in 28-day cycles. Concurrent somatostatin analog (SSA) use was allowed if there was disease progression after ≥ 3 mos on a stable dose. The primary endpoint was progression-free survival (PFS); secondary endpoints were safety and other efficacy measures.

Results

Of the 43 pts enrolled, 34 evaluable pts (20 M/14 F; median age 59 y) were mostly grade 2 pNET (21/34, 62%) or GI NET (12/34, 35%). At data cut-off date on March 6, 2024, treatment is still ongoing in 8 pts. With a median follow up of 12.8 mos (95% CI 8.2–20.1 mos) and 3 prior therapies, the mPFS has reached 10.3 mos (95% CI 5.9–23.8 mos), exceeding the historical 4–6 mos of placebo groups reported in sunitinib and everolimus Phase 3 trials. Subgroup analysis of CVM-1118 with concurrent SSA showed an mPFS of 25.4 mos. Best overall response was 2.9% partial response (tumor reduction ≥ 77%). Treatment-related adverse events (TRAEs) occurred in 19 of 43 (44%) pts; 80% of events were grade 1/2. Most common ≥ grade 3 TRAEs were anemia and neutropenia (5%); 3 (7%) pts discontinued due to TRAEs, but no serious TRAE was reported. On Day 1 of dosing, the mean drug exposure was C_max 385 ng/mL and AUC_0-24 1941 ng·hr/mL, with high intersubject variability.

Conclusions

CVM-1118 presents a promising therapy for advanced NETs with superior tolerability and safety profile to the current targeted therapies and warrants further development.

Clinical trial identification

NCT03600233, first posted 2018.07.26.

Editorial acknowledgement

Legal entity responsible for the study

TaiRx, Inc.

Funding

TaiRx, Inc.

Disclosure

M. Chen: Financial Interests, Personal, Invited Speaker: MSD, AstraZeneca; Financial Interests, Personal, Advisory Board: Ono, Astellas, Eli Lilly, TTY; Financial Interests, Personal, Steering Committee Member: Roche; Financial Interests, Personal and Institutional, Local PI: Roche, MSD, Amgen, AstraZeneca, Ono; Financial Interests, Personal and Institutional, Research Grant: Boehringer Ingelheim; Non-Financial Interests, Personal, Product Samples: Eli Lilly. L. Bai: Financial Interests, Personal, Advisory Board: Amgen, Astellas; Financial Interests, Personal, Invited Speaker: Ono; Non-Financial Interests, Personal, Product Samples, Support of a investigator-initiated clinical trial: Eisai. J. Chen: Financial Interests, Personal, Other, Clinical trial Principle investiagator: BMS/Ono, MSD, Taiho, Merck, Janssen, Amgen, Roche; Financial Interests, Personal, Advisory Board, expert advise meeting: Astellas, Zai LAB, CStoone; Financial Interests, Personal, Invited Speaker: TTY; Financial Interests, Personal, Other, Clinical trial Principle investiagatorspeaker: AstraZeneca; Non-Financial Interests, Leadership Role, Presisdent: Taiwan Oncology Society. Y. Chen, C. Chen: Financial Interests, Personal, Full or part-time Employment: TaiRx, Inc.; Financial Interests, Personal, Stocks/Shares: TaiRx, Inc. T. Chao: Financial Interests, Personal, Full or part-time Employment: TaiRx, Inc. Y. Chu: Financial Interests, Personal, Full or part-time Employment, I am the Senior VP and Board member of TaiRx, Inc.: TaiRx, Inc.; Financial Interests, Personal, Stocks/Shares: TaiRx, Inc. D. Chien: Financial Interests, Personal, Member of Board of Directors, Currently serve as CEO and board member: TaiRx, Inc; Financial Interests, Personal, Stocks/Shares, Own shares of TaiRx stock: TaiRx, Inc. All other authors have declared no conflicts of interest.