An Open-label Phase 1 Trial of the Safety and Efficacy of Daily Subcutaneous SPL-108 Injections When Used In Combination With Paclitaxel In Patients With Platinum-resistant, CD44+, Advanced Ovarian Epithelial Cancer

Up to 18 women with ovarian cancer will administer up to two injections of SPL-108 daily in combination with weekly doses of Paclitaxel. They will be monitored for safety and efficacy for up to 6 months, until disease progression or unacceptable toxicity.

Start Date10 Mar 2017

Sponsor / Collaborator

Splash Pharmaceuticals, Inc.

100 Clinical Results associated with SPL-108

100 Translational Medicine associated with SPL-108

100 Patents (Medical) associated with SPL-108

Literatures (Medical) associated with SPL-108

01 Jan 2025·Translational Oncology

SPL-108 mitigates metastasis and chemoresistance in tubo-ovarian carcinoma

Article

Author: Levine, Douglas A ; Van Oudenhove, Elke ; Pereira, Luiza ; Lara, Olivia D ; Hacker, Kari E ; Misirlioglu, Selim

BACKGROUNDOvercoming the heterogeneous mechanisms of metastasis and chemoresistance will improve outcomes for women with tubo-ovarian carcinomas (TOCs). CD44 expression has been shown to be associated with poor prognosis and advanced disease in TOCs. In addition, studies have shown a link between chemoresistance and CD44 pathways. Given the therapeutic implications of targeting CD44, this manuscript examines the biologic effects of a novel CD44 modulator, SPL-108, in TOCs.MATERIALS AND METHODSWe assessed the effects of SPL-108 on chemosensitivity and migration in a panel of ovarian cancer cell lines with varied CD44 and MDR1 expression. In vitro experiments (cell viability assay, Western blot analysis, Calcein AM fluorescence assay, and migration assay) were carried out to determine the functional effects of SPL-108 in TOCs.FINDINGSOvarian cancer cell lines OVCAR5 and OVCAR8 expressed higher protein levels of CD44 as demonstrated through Western Blot analysis. SPL-108 treatment significantly decreased the number of migrating cells in OVCAR8, OVCAR5 and OVCAR3 cell lines and migratory response was independent of CD44 expression. Treatment with SPL-108 led to significant accumulation of the MDR1 substrate Calcein in OVCAR5, OVCAR8 and OVCAR3 cells lines compared to verapamil treated positive control cells. Retention of Calcein after SPL-108 treatment was seen in cell lines with high MDR1 protein expression and no Calcein retention was seen in cells lacking MDR1 expression, suggesting SPL-108 inhibits MDR1.CONCLUSIONSSPL-108 treatment has anti-metastatic properties and may play a role in chemoresistance in preclinical models of TOCs independent of CD44 expression. Ongoing in vitro and in vivo studies will help guide further clinical development of SPL-108.

01 Aug 2022·International Journal of Gynecologic Cancer

Phase I trial of daily subcutaneous SPL-108 injections in combination with paclitaxel in patients with platinum resistant CD44+ advanced ovarian epithelial cancer

Article

Author: de Meritens, Alexandre Buckley ; Wright, Jason D ; Hou, June ; Palmer, Joycelynne ; Rodriguez-Rodriguez, Lorna ; Girda, Eugenia ; Song, Mihae ; Yu, Hua ; Chan, Nancy ; Kohut, Adrian ; Martincuks, Antons ; Finlayson, Malcolm ; Stephenson, Ruth ; Tergas, Ana I ; Chekmareiva, Marina ; Vattakalam, Reena ; Leiser, Aliza ; Nelson, David

ObjectivePreclinical evidence and early clinical trials have demonstrated the activity of SPL-108, a targeted agent that inhibits CD44 mediated induction of multidrug resistance specifically to paclitaxel and platinum agents. We conducted a phase I, open label, dose escalation study of the safety and tolerability of the combination of SPL-108 with weekly paclitaxel in patients with platinum resistant CD44+ ovarian, primary peritoneal, or fallopian tube cancer.MethodsPatients with platinum resistant histologically proven epithelial ovarian, primary peritoneal, or fallopian tube cancers and measurable disease according to RECIST (Response Evaluation Criteria in Solid Tumours) version 1.1 were selected. Tumors were tested for CD44 expression for eligibility, defined as strong (+++) or moderate (++) staining in ≥20% of the tumor tissue or diffuse + staining. Patients were treated with daily and then twice daily SPL-108 subcutaneous injections and weekly intravenous paclitaxel on days 1, 8, and 15 of a 28 day cycle. Endpoints included safety, determination of maximum tolerated dose, and efficacy. Tumors underwent comprehensive genomic profiling, and cell lines and western blotting were used to study markers of response.ResultsWe screened 16 patients, and 14 were enrolled based on CD44+ expression. A total of 86% of patients had high grade serous tumors and all had received multiple prior therapies. There were no grade 4–5 toxicities. One patient had grade 3 peripheral sensory neuropathy attributed to paclitaxel and one patient developed presumed colonic perforation attributed to the study drug. No dose reductions or treatment discontinuations were required. All patients tolerated the maximum planned dose; no maximum tolerated dose was reached. Overall response rate was 36%; 5 (36%) patients had partial response and 5 (36%) patients had stable disease.ConclusionsThe combination of SPL-108 with weekly paclitaxel was safe and well tolerated. Encouraging antitumor activity was observed, with 72% of patients deriving a clinical benefit.Trial registrationNCT03078400.

100 Deals associated with SPL-108

R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
Endometrial Carcinoma	Phase 3	US	Splash Pharmaceuticals, Inc.	29 Jul 2018
Prostatic Cancer	Phase 3	US	Splash Pharmaceuticals, Inc.	16 Jul 2018
Liver Cancer	Phase 3	US	Splash Pharmaceuticals, Inc.	13 Jul 2018
Ovarian Cancer	Phase 2	-	Splash Pharmaceuticals, Inc.	-
Brain Cancer	Phase 1	US	Splash Pharmaceuticals, Inc.	09 Jul 2018
Breast Cancer	Phase 1	US	Splash Pharmaceuticals, Inc.	09 Jul 2018
Dystrophy, Macular	Phase 1	US	Splash Pharmaceuticals, Inc.	08 Apr 2018
Rheumatoid Arthritis	Phase 1	US	Splash Pharmaceuticals, Inc.	07 Apr 2018
Platinum-Resistant Epithelial Ovarian Carcinoma	Preclinical	US	Splash Pharmaceuticals, Inc.	10 Mar 2017

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03078400 (Pubmed)	Phase 1	Platinum-Resistant Epithelial Ovarian Carcinoma	14	SPL-108 + Paclitaxel	(hnwofqbjcr) = One patient had grade 3 peripheral sensory neuropathy attributed to paclitaxel cezvkrqimo (mgoeqnwjnq ) View more	Positive	24 Jun 2022
SGO	Not Applicable	Fallopian Tube High Grade Serous Adenocarcinoma	-	SPL-108	fswtibmthi(yvhvxqbwjt) = No toxicity was observed with SPL-108 monotherapy xvfjyabpfa (wojliuhfpd )	-	01 Aug 2021
SGO	Not Applicable	Fallopian Tube High Grade Serous Adenocarcinoma	-	SPL-108 (Control)		-	01 Aug 2021
NCT03078400 (ASCO2020) Manual	Phase 1	Ovarian Cancer CD44 Positive	14	paclitaxel+SPL-108	(zaqdcfwssg) = htzwimgswd qjnczznwct (hxqsjpkvwt ) View more	Positive	29 May 2020

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