Abstract
CVM-1118: A potent oral anti-vasculogenic mimicry (VM) agent in combination with nivolumab in patients with unresectable advanced hepatocellular carcinoma (HCC)—A phase IIa study.
Author
person
Chia-Jui Yen
Department of Surgery, National Cheng Kung University Hospital, Tainan, Taiwan
info_outline
Chia-Jui Yen, Yi-Hsiang Huang, Kun-Yun Yeh, Pei-Jer Chen, Sheng-Nan Lu, John Gutheil, Teresa J. Melink, Yen-Ling Chen, Chun-Man Chen, Ting-Yu Chao, Yi-Wen Chu, Du-Shieng Chien
Full text
Authors
person
Chia-Jui Yen
Department of Surgery, National Cheng Kung University Hospital, Tainan, Taiwan
info_outline
Chia-Jui Yen, Yi-Hsiang Huang, Kun-Yun Yeh, Pei-Jer Chen, Sheng-Nan Lu, John Gutheil, Teresa J. Melink, Yen-Ling Chen, Chun-Man Chen, Ting-Yu Chao, Yi-Wen Chu, Du-Shieng Chien
Organizations
Department of Surgery, National Cheng Kung University Hospital, Tainan, Taiwan, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, Department of Internal Medicine, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan, Division of Hepato-Gastroenterology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan, SciQuus Oncology, Inc, La Jolla, CA, TaiRx, Inc., Taipei, Taiwan
Abstract Disclosures
Research Funding
TaiRx, Inc.
Background:
CVM-1118 is a potent anti-tumor new chemical entity with multiple mechanisms of action including induction of apoptosis, cell cycle arrest, and inhibition of VM network formation. This study evaluated the anti-tumor effect and safety profile of CVM-1118 plus nivolumab in patients with progressive unresectable advanced HCC following the first-line therapy with TKIs.
Methods:
Eligible pts had unresectable advanced HCC and were refractory to prior systemic therapy (e.g., sorafenib, lenvatinib, regorafenib, and/or ramucirumab), with the exception of prior immunotherapy. Patients received oral CVM-1118 at 200 mg BID (400 mg daily) in combination with intravenous nivolumab at 240 mg Q2W in 28-day cycles. The primary endpoint of objective response rate was evaluated using mRECIST. The secondary endpoints were overall response rate (ORR) (per RECIST 1.1), progression free survival (PFS), disease control rate (DCR), and duration of overall response (DoR).
Results:
A total of 31 evaluable pts were enrolled (25 M/6 F; median age 65 y, range 44–80 y). All patients were Child Pugh A, BCLC stage B (13%, n = 4) or C (87%, n = 27) at the start of treatment. The median number of prior lines of therapy was 1 (range 1–2). The duration of CVM-1118 and nivolumab treatment ranged from 1.5–15.0 mos (median 3.1 mos) with 5/31 (16%) pts remaining on treatment for ≥ 4.6 mos (range 4.67–15.0 mos). The best ORR was 19.4% (mRECIST) (2 CR (6%), 4 PR (13%)), with remaining responses including 11 SD (36%) and 14 PD (45%). The DCR was 54.8% (95% CI 37.3–72.3%), the median PFS was 3.53 mos (95% CI 1.9–5.4 mos) and the median DoR was 10.4 mos (95% CI 2.8–13.7 mos). The most common treatment-related AEs ³ grade 3 included AST increased (12.9%), neutrophil count decreased (9.7%), anemia (6.5%), and WBC decreased (6.5%). As opposed to therapy with atezolizumab plus bevacizumab, gastrointestinal hemorrhage and hypertension were not observed in this study. Pharmacokinetics data demonstrated that CVM-1118 was rapidly metabolized to CVM-1125 in all pts following administration. On Day 1, the mean drug exposure of CVM-1125 was C
max
564 ng/mL and the AUC
0-24
was 2154 ng·hr/mL. Intersubject variability of drug exposure appeared to be high; the T
1/2
of CVM-1125 was ~1.7 hr.
Conclusions:
CVM-1118 combined with nivolumab demonstrated clinical activity in advanced HCC pts with a safety profile that appears favorable compared to atezolizumab plus bevacizumab. These data support further development of the combination of CVM-1118 and nivolumab in pts with unresectable advanced HCC. Clinical trial information: NCT05257590.
7 organizations
8 drugs
28 targets
Drug
CVM-1118Drug
nivolumabDrug
sorafenibDrug
lenvatinibDrug
RegorafenibDrug
ramucirumabDrug
AtezolizumabDrug
bevacizumabTarget
FLT-3Target
FGFR3Target
c-KitTarget
induction of apoptosisTarget
FGFR4Target
VEGFR3Target
VEGFR1Target
RAF-1Target
B-RAFTarget
cell cycle arrestTarget
VEGF and c-MET pathwaysTarget
VEGFR-1Target
VEGFR2Target
KITTarget
PDGFR-αTarget
FGFR1Target
PDGFR-alphaTarget
PDGFR-βTarget
PD-1Target
VEGF receptor 2Target
TIE2Target
RETTarget
VEGFR-3Target
FGFR2Target
VEGFR-2Target
FGFRaTarget
PD-L1Organization
Division of Hepato-Gastroenterology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, TaiwanOrganization
SciQuus Oncology, Inc, La Jolla, CAOrganization
TaiRx, Inc., Taipei, Taiwan