Phase I study of Minnelide and paclitaxel combination chemotherapy in refractory gastric cancer (GC).

Authors

null

Jeeyun Lee

Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea;

Jeeyun Lee , Seung Tae Kim , Won Ki Kang , Ashok Saluja

Organizations

Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea; , Sylvester Comprehensive Cancer Center, Department of Surgery, University of Miami, Miami, FL;

Research Funding

No funding received
None.

Background: Minnelide is a prodrug that rapidly releases the active compound triptolide when exposed to phosphatases in the bloodstream. Triptolide is a diterpene that has been shown to inhibit tumor cell proliferation and induce apoptosis in various cancer types. The anti-tumor effect of triptolide is the result of inhibition of heat shock protein (HSP) 70 expression. In GC Minnelide inhibits Sp1 to decrease HSP70 and induce cell death in preclinical data. Methods: This phase 1 trial was designed to determine the maximum tolerated dose (MTD) of Minnelide monotherapy and the MTD of Minnelide in combination with paclitaxel in refractory GC patients. There were 6 cohorts tested in this trial: cohort A: Minnelide 1 mg qd D1-21, q 28 days; cohort B: Minnelide 1.25 mg qd D1-21, q 28 days; cohort C: 1.5 mg qd D1-21, q 28 days; cohort D: Minnelide 0.25 mg D1-21 + weekly paclitaxel 60 mg/m2 on D1, D8, D15; cohort E: Minnelide 0.5 mg qd D1-21+ weekly paclitaxel 80 mg/m2 on D1, D8, D15; cohort F: Minnelide 0.75 mg qd D1-21+ weekly paclitaxel 80 mg/m2 D1, D8, D15. Results: From Feb 2021 to Sep 2022, 23 GC patients were enrolled (cohort A – C, N=10; cohort D-F, N=12). All patients had metastatic disease at the time of study enrollment. 20 of 23 patients received the study treatment as >= 3rd-line (range, 2 – 6th line). In all, 3 patients had HER2 positive GC and 10 patients had PDL1 + tumor. In the monotherapy cohorts, there were no DLTs observed, and the regimen was tolerated well. One patient achieved confirmed PR which lasted for 6 months. For the combination arm (cohort D-F), there were no DLTs observed. Of the 11 patients who were evaluable for treatment response, there were 1 PR, 5 SDs and 5 PDs. Two of five patients who achieved stable disease had durable stable disease for > 6 months on study treatment. In the combination cohorts, the most common adverse events of any grade were neutropenia; however, there was no neutropenic fever or treatment related mortality. Conclusions: Minnelide in combination with weekly paclitaxel demonstrated promising anti-tumor activity with durable responses in refractory AGC. Clinical trial information: Underreview.

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Abstract Details

Meeting

2023 ASCO Gastrointestinal Cancers Symposium

Session Type

Poster Session

Session Title

Poster Session A: Cancers of the Esophagus and Stomach and Other GI Cancers

Track

Esophageal and Gastric Cancer,Other GI Cancer

Sub Track

Therapeutics

Clinical Trial Registration Number

Underreview

Citation

J Clin Oncol 41, 2023 (suppl 4; abstr 414)

DOI

10.1200/JCO.2023.41.4_suppl.414

Abstract #

414

Poster Bd #

H17

Abstract Disclosures