Abstract 1057P
Background
CS1003 is a novel humanized IgG4 anti-PD-1 monoclonal antibody. In phase 1a dose-escalation, CS1003 showed a well-tolerated safety profile with no dose-limiting toxicity, and a wide therapeutic window at doses up to 10 mg/kg Q3W (maximum administrated dose, MAD) in patients (pts) with solid tumors. Two fixed-dose regimens were explored in the phase Ib portion of this ongoing clinical trial in pts with selected solid tumors.
Methods
Pts were enrolled in cohort A (200 mg Q3W) or cohort B (400 mg Q6W) to receive CS1003 intravenously. Safety, preliminary tumor activity (overall response per RECIST v1.1 by investigators) and PK were assessed.
Results
As of 21 Mar 2020, 29 and 30 pts were enrolled in cohorts A and B, with a median treatment duration of 15.0 (range: 3.0-50.4) and 14.4 (range: 4.7-27.7) weeks, respectively. Following the first dose, the mean Cmax value of CS1003 in cohort B was around doubling of that in cohort A (112 vs 44 μg/ml) but lower than that (189 μg/ml) at the MAD, demonstrating sufficient safety margin. The mean Ctrough value of cohorts A and B were 9.2 and 18.8 μg/ml, respectively, expecting a complete PD-1 receptor occupancy throughout the dosing intervals with both regimens. The steady-state PK data of cohort B will be updated. In cohorts A and B, 97% (28/29) and 93% (28/30) pts had treatment-emergent adverse events; 41% (12/29) and 47% (14/30) pts had all-grade treatment-related adverse events (TRAEs), respectively. The TRAE profiles were comparable in both cohorts overall with two Grade (G) ≥ 3 events (G3 dermatitis and G4 Type 1 diabetes mellitus in cohort B), and the rest were G1/2. Among the 29 efficacy-evaluable pts in cohort A, there were 3 complete response (2 confirmed), 3 partial response (PR, 2 confirmed) and 5 stable disease (SD). Among the 27 efficacy-evaluable pts in cohort B, there were 4 PR (1 confirmed) and 13 SD.
Conclusions
The preliminary safety and efficacy profiles of CS1003 at 200 mg Q3W and 400 mg Q6W appear comparable. PK data are also supportive of selecting either regimen for future development while 400 mg Q6W offers greater dosing flexibility to pts and physicians.
Clinical trial identification
NCT03475251.
Editorial acknowledgement
Legal entity responsible for the study
CStone Pharmaceuticals (Su Zhou) Co., Ltd.
Funding
CStone Pharmaceuticals (Su Zhou) Co., Ltd.
Disclosure
B. Markman: Honoraria (self), Advisory/Consultancy: Amgen; Honoraria (self), Advisory/Consultancy: Novartis. J. Coward: Honoraria (institution), Advisory/Consultancy: Takeda; Honoraria (institution), Advisory/Consultancy: MSD; Shareholder/Stockholder/Stock options: Loon; Research grant/Funding (self): MedImmune. D. Kotasek: Honoraria (institution), Advisory/Consultancy: SunBio Pharmaceuticals. M.P. Brown: Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Novartis; Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: BMS; Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: MSD; Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Amgen; Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: GSK; Non-remunerated activity/ies, International steering committee for MO25515 Study: Roche; Non-remunerated activity/ies, Country Lead for CA033 Study: Celgene; Leadership role: Centre for Cancer Biology Faculty Member; Non-remunerated activity/ies: Member, Medical Oncology Group of Australia; Non-remunerated activity/ies: Member, American Society of Clinical Oncology; Non-remunerated activity/ies: Mebmber, AACR. J. Kuo: Travel/Accommodation/Expenses: Zucero Therapeutics; Travel/Accommodation/Expenses: Bristol-Myers Squibb; Travel/Accommodation/Expenses: MSD Oncology. A. Prawira: Leadership role, Research grant/Funding (institution), PI role: Arcusbio; Advisory/Consultancy, Leadership role, Research grant/Funding (institution), PI role: Akesobio; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Bayer; Leadership role, Research grant/Funding (institution), PI role: Beigene; Leadership role, Research grant/Funding (institution), PI role: Roche/Genentech; Leadership role, Research grant/Funding (institution), PI role: BMS; Research grant/Funding (institution): Apollomics; Leadership role, Research grant/Funding (institution), PI role: Corvus; Advisory/Consultancy, Leadership role, Research grant/Funding (institution), PI role: CStone; Advisory/Consultancy, Leadership role, Research grant/Funding (institution), PI role: Macrogenics; Advisory/Consultancy, Leadership role, Research grant/Funding (institution), PI role: Five Prime; Leadership role, Research grant/Funding (institution), PI role: Henlius; Leadership role, Research grant/Funding (institution), PI role: Eli Lilly; Leadership role, Research grant/Funding (institution), PI role: MSD; Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy, Leadership role, Research grant/Funding (institution), PI role: Virogin; Research grant/Funding (institution): Janssen; Leadership role, Research grant/Funding (institution), PI role: GSK; Advisory/Consultancy, Research grant/Funding (institution): QBiotics; Non-remunerated activity/ies: Member of EVIQ reference committee; Non-remunerated activity/ies: Member of NSW Virtual Care Community of Practice. R. Strother: Research grant/Funding (institution): Daiichi Sankyo; Research grant/Funding (institution): Imugene; Research grant/Funding (institution): Sillagen; Research grant/Funding (institution): Roche; Research grant/Funding (institution): Dynavax; Research grant/Funding (institution): MSD; Research grant/Funding (institution): BMS; Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): Kinex; Research grant/Funding (institution): CStone; Research grant/Funding (institution): Zhejiang Medicine Co Ltd; Research grant/Funding (institution): Regeneron; Research grant/Funding (institution): ImClone; Research grant/Funding (institution): Intellikine; Research grant/Funding (institution): Millenium; Research grant/Funding (institution): Tracon; Research grant/Funding (institution): Sanofi; Leadership role: Committee Member for Pharmac-the New Zealand Government Health Technology Assessment entity. Q. Zhang, A. Tse: Shareholder/Stockholder/Stock options, Full/Part-time employment: CStone Pharmaceuticals (Su Zhou) Co., Ltd. L. Wang, R. Chen, Y. Ma, Z. Qin: Full/Part-time employment: CStone Pharmaceuticals (Su Zhou) Co., Ltd. All other authors have declared no conflicts of interest.