NCT05145569

Antitumor Activity of Neoadjuvant Chemotherapy with or Without HCW9218 in Metastatic Advanced Stage Ovarian Cancer

A Phase 2 Open-label Study to Assess the Antitumor Activity of Neoadjuvant Chemotherapy with or Without HCW9218 in Patients with Metastatic Advanced Stage Ovarian Cancer

• Status: Withdrawn
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: Haider Mahdi · Academic / Other
• Sex: Female
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

In this study, the safety, tolerability, and anti-tumor activity of HCW9218 in combination with chemotherapy will be assessed in patients with advanced stage ovarian cancer undergoing neoadjuvant chemotherapy.

Detailed description

Existing data supports a potential role and synergistic activity between TGF-β inhibitors and PD1 TGF-β has been investigated in ovarian cancer and it is suggested to play a dominant role as a potent inducer of ovarian cancer invasiveness and metastasis in additional studies \[36\]. In fact, TGF-β ligand and TGF-β receptor I and II are strongly expressed in ovarian tumors especially high-grade ovarian cancers. Further, TGF-β is abundantly secreted into the tumor microenvironment by cancer and stromal cells in this cancer. TGF-β expression has been shown to significantly higher in ovarian cancer tissue especially advanced stage disease compared to healthy tissue or borderline tumors. Inhibiting senescence in the immune compartment may have a profound effect on the cytotoxic functions of both innate and adaptive immune cells. This study aims to examine markers of senescence on immune cells obtained from blood throughout the proposed trial. We hypothesize that HCW9218 will act as a senolytic by "trapping" excess TGF-β, therefore inhibiting its ability to promote senescence. We believe that this combined with the immune activating effect of IL-15 will be a biologically relevant therapeutic with potential to at least partially reverse therapy induced senescence (TIS) or in the future, perhaps have an effect even on physiologic aging.

Conditions

• Ovarian Cancer

Interventions

Type	Name	Description
DRUG	Carboplatin AUC 5 and paclitaxel	Carboplatin AUC 5 and paclitaxel combination chemotherapy is very well tolerated and highly effective for the treatment of ovarian cancer and thus is standard of care therapy. Both carboplatin and paclitaxel are chemotherapy agents that are designed to kill and slow the growth of cancer cells.
DRUG	HCW9218	HCW9218 is an immunotherapeutic comprising transforming growth factor-b (TGF-b) receptor II and interleukin (IL)-15/IL-15 receptor a domains.

Timeline

• Start date: 2024-05-10
• Primary completion: 2026-05-31
• Completion: 2028-01-31
• First posted: 2021-12-06
• Last updated: 2025-01-01

Regulatory

• FDA-regulated drug study