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Clinical Trial
. 2024 Nov;29(11):1684-1695.
doi: 10.1007/s10147-024-02589-x. Epub 2024 Sep 20.

Preliminary results from ASCENT-J02: a phase 1/2 study of sacituzumab govitecan in Japanese patients with advanced solid tumors

Yoichi Naito  1 , Seigo Nakamura  2 , Nobuko Kawaguchi-Sakita  3 , Takanori Ishida  4 , Takahiro Nakayama  5 , Yutaka Yamamoto  6 , Norikazu Masuda  7 , Koji Matsumoto  8 , Takahiro Kogawa  9 , Kazuki Sudo  10 , Akihiko Shimomura  11 , Catherine Lai  12 , Danjie Zhang  12 , Yuki Iwahori  13 , Dianna Gary  12 , Danh Huynh  12 , Hiroji Iwata  14
Affiliations
Clinical Trial

Preliminary results from ASCENT-J02: a phase 1/2 study of sacituzumab govitecan in Japanese patients with advanced solid tumors

Yoichi Naito et al. Int J Clin Oncol. 2024 Nov.

Abstract

Background: Sacituzumab govitecan (SG) is a Trop-2-directed antibody-drug conjugate approved outside Japan for second-line and later metastatic triple-negative breast cancer (mTNBC), based on the ASCENT study (NCT02574455). We report SG safety and efficacy in an open-label, phase 1/2 bridging study in Japanese patients with advanced solid tumors (ASCENT-J02; NCT05101096; jRCT2031210346).

Methods: Phase 1 was a standard 3 + 3 design. Patients received intravenous SG 6 mg/kg, escalating to 10 mg/kg, on Days 1 and 8 per 21-day cycle; primary endpoints were safety, incidence of dose-limiting toxicity/toxicities (DLTs), and determination of the recommended phase 2 dose (RP2D). In the multicohort phase 2 study, patients in the mTNBC cohort with previously treated disease received SG at the RP2D; primary endpoint was independent review committee (IRC)-assessed objective response rate (ORR; RECIST v1.1). Safety was a secondary endpoint.

Results: In phase 1 (N = 15), one DLT (grade 3 elevated transaminases) occurred with SG 10 mg/kg; RP2D was SG 10 mg/kg regardless of UGT1A1 status. In phase 2, 36 patients with mTNBC received SG 10 mg/kg. At median follow-up of 6.1 months, IRC-assessed ORR was 25.0% (95% CI 12.1-42.2; P = 0.0077). Median progression-free survival was 5.6 months (95% CI 3.9-not reached [NR]); median overall survival was NR. No treatment-emergent adverse events led to discontinuation or death.

Conclusions: SG RP2D was established as 10 mg/kg in Japanese patients. SG showed efficacy in Japanese patients with previously treated mTNBC, a manageable safety profile, and no new safety signals, consistent with the previous ASCENT study.

Keywords: Antibody–drug conjugate; Japanese patients; Metastatic triple-negative breast cancer; Phase 2; Sacituzumab govitecan.

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Conflict of interest statement

YN reports research funding from Gilead Sciences, Inc; and honoraria from AstraZeneca, Eisai, Ono, Guardant, Takeda, Eli Lilly, Novartis, Pfizer, Chugai, PDR Pharma, Nihon Kayaku, Taiho, Bristol, Bayer, and Daiichi Sankyo. SN, TI, TN, and TK report nothing to disclose. NKS reports research funding from Gilead Sciences, Inc; and honoraria from Chugai, Daiichi Sankyo, Kyowa Kirin, Nippon Kayaku, Pfizer, Taiho, Eisai, AstraZeneca, and Zena. YY reports honoraria from AstraZeneca, Chugai, Kyowa-Kirin, Novartis, Lilly, Pfizer, Daiichi Sankyo, Nippon-Kayaku, Taiho, Eisai, Takeda, MSD, Sysmex and Exact Science; and other financial or non-financial interests with the Japanese Breast Cancer Society and the Japan Breast Cancer Research Group. NM reports honoraria from AstraZeneca, Chugai, Daiichi Sankyo, Eli Lilly, and Pfizer; and uncompensated leadership roles for JBCRG, Japanese Breast Cancer Society (JBCS), and Japan Society of Clinical Oncology (JSCO). KM reports research funding from Gilead Sciences, Inc; and honoraria from MSD, Kyowa-Kirin, Eli Lilly, Daiichi-Sankyo, Eisai, and Chugai. KS reports research funding from Amgen, AstraZeneca, Daiichi Sankyo, PRA Health Sciences, NanoCarrier, Takeda, Gilead Sciences, Inc, and Merck; and honoraria from Astra Zeneca, Eisai, Bayer Yakuhin, Pfizer, Nihon Medi-Physics, and MSD. AS reports research funding from Gilead Sciences, Inc; and honoraria from Chugai, Eli Lilly, AstraZeneca, Gilead Sciences, Inc, Exact Science, Daiichi Sankyo, Kyowa-Kirin, MSD, Pfizer, and Nihon Medi-Physics. CL, DZ, YI, DG, and DH report employment and stock or other ownership interests in Gilead Sciences, Inc. HI reports research funding from Chugai, Daiichi Sankyo, and AstraZeneca; consulting fees from Gilead Sciences, Inc; and honoraria from Chugai, Daiichi Sankyo, and AstraZeneca.

Figures

Fig. 1
Fig. 1
ASCENT-J02 study design. aIn the event that a DLT is observed in two out of six patients, enrollment of Cohort A3 at 8 mg/kg will begin; de-escalation to Cohort A3 was not needed.bEarlier adjuvant or neoadjuvant therapy for more limited disease will qualify as one of the required prior regimens if the development of unresectable, locally advanced, or metastatic disease occurred within 12 months after completion of chemotherapy. 2L second-line, 3L third-line, 4L fourth-line, DLT dose-limiting toxicity, DMC data monitoring committee, DOR duration of response, HR + /HER2 − hormone receptor-positive/human epidermal growth factor receptor 2-negative, IRC independent review committee, IV intravenous, mBC metastatic breast cancer, mTNBC metastatic triple-negative breast cancer, mUC metastatic urothelial cancer, ORR objective response rate, OS overall survival, PFS progression free survival, RECIST v1.1 Response Evaluation Criteria in Solid Tumors v1.1, RP2D recommended phase 2 dose, SG sacituzumab govitecan, SOC standard of care, TEAE treatment-emergent adverse event, TTR time to response, UGT1A1 UDP glucuronosyltransferase family 1 member A1
Fig. 2
Fig. 2
Patient disposition in A phase 1 and B phase 2 mTNBC of the ASCENT-J02 study. aAll deaths were due to disease progression and occurred more than 30 days after the last dose. bAll four deaths were due to disease progression; three deaths occurred more than 30 days after the last dose and one death occurred within 30 days of the last dose. mTNBC metastatic triple-negative breast cancer
Fig. 3
Fig. 3
Kaplan–Meier estimate of PFS by A independent review committee and B by investigator assessment in the phase 2 dose-expansion mTNBC cohort of ASCENT-J02. Median follow-up for OS was 6.1 months, the primary analysis for efficacy was performed ~ 18 weeks after the last patient enrolled. CI confidence interval; IRC independent review committee; mTNBC metastatic triple-negative breast cancer; NR not reached; PFS progression-free survival
Fig. 4
Fig. 4
Any-grade TEAEs (≥ 25%) in the phase 2 dose-expansion mTNBC cohort (N = 36). aNeutropenia includes neutrophil count decreased. bLeukopenia includes white blood cell count decreased. cAnemia includes hemoglobin decreased and red blood cell count decreased. mTNBC metastatic triple-negative breast cancer; TEAE treatment-emergent adverse event
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