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

NCT05145569 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: HCC 21-162
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Ovarian Cancer

Keywords

TGFβ receptor II (TGFβRII or TGFβ Trap); PD-L1

Outcome Measures

Primary Outcomes (4)

• Safety - Dose Limiting Toxicities (DLT)

  A Dose Limiting Toxicity (DLT) is defined hematologic or non-hematologic toxicity (assessed in accordance with NCI CTCAE v 5.0), clearly attributable to HCW9218 (experimental agent) which cause any immune-related grade 3 or grade 4, or recurrent grade 2 toxicities, requiring discontinuation of HCW9218 or treatment delay for more than 4 weeks. The criteria for stopping will be P(P(DLT)\>0.2)\>0.66, which will be evaluated after every 5 patients on the chemotherapy plus HCW9218 arm have completed their safety observation period (four cycles). The probability statement will be assessed using a beta-binomial rule with a prior that assumes unacceptable toxicity will occur in 10% of patients (α=1 and β=9).

  Up to 8 weeks

• Adverse Events Related to Treatment

  Incidence, nature and severity of adverse events (AEs) graded according to NCI CTCAE v5.0.

  Up to 12 months

• Complete Pathologic Response

  Proportion of patients that experience a complete absence of cancer after study treatment as determined by pathological/histological assessment of tissue samples.

  Up to 36 months

• CD8+ T-cell characterization

  CD8+ T-cell infiltration and other alterations in tumor immune microenvironment.

  Up to 12 months

Secondary Outcomes (13)

• Progression-free Survival (PFS) at 6 months

  Up to 6 months

• Progression-free Survival (PFS) at 12 months

  Up to 12 months

• Progression-free Survival (PFS) at 18 months

  Up to 18 months

• Progression-free Survival (PFS)

  Up to 5 years

• Overall Survival (OS) at 6 months

  Up to 6 months

Study Arms (2)

Carboplatin/paclitaxel + HCW9218

EXPERIMENTAL

HCW9218 in combination with chemotherapy including carboplatin AUC 5 and paclitaxel 175 mg/m2 on Day 1 of the 21-day cycle

Drug: Carboplatin AUC 5 and paclitaxel; Drug: HCW9218

Carboplatin/paclitaxel

ACTIVE COMPARATOR

Carboplatin AUC 5 and paclitaxel 175 mg/m2 on Day 1 of the 21-day cycle

Drug: Carboplatin AUC 5 and paclitaxel

Interventions

Carboplatin AUC 5 and paclitaxel DRUG

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.

Also known as: Carbo/Taxol

Carboplatin/paclitaxel; Carboplatin/paclitaxel + HCW9218

HCW9218 DRUG

HCW9218 is an immunotherapeutic comprising transforming growth factor-b (TGF-b) receptor II and interleukin (IL)-15/IL-15 receptor a domains.

Carboplatin/paclitaxel + HCW9218

Eligibility Criteria

• Age: 18 Years+
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
• Provision of signed and dated, written informed consent form prior to any mandatory study specific procedures, sampling, and analyses.
• A female participant is eligible to participate if she is not pregnant (see Appendix E), not breastfeeding, and at least one of the following conditions applies:
• d1. Not a woman of childbearing potential (WOCBP) as defined in Appendix E
• d2. A WOCBP who agrees to follow the contraceptive guidance in Appendix E during the treatment period and for at least 120 days after the last dose of study treatment.
• Diagnosis/Condition for Entry into the Trial:
• World Health Organization (WHO)/Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 1 or 2 at enrollment.
• Must have a life expectancy of at least 12 weeks
• Patients with histologically or cytologically confirmed epithelial ovarian, fallopian or primary peritoneal cancer. patients should have diagnosis of advanced stage (III-IV) ovarian cancer who are planned to have neoadjuvant chemotherapy with carboplatin and paclitaxel.
• High grade serous histology
• Patients have to be chemo-naïve with no prior chemotherapy or any therapy for ovarian cancer.
• Confirmation of measurable disease based on RECIST 1.1 by investigators at Screening will be used to determine patient eligibility and imaging shows at least 1 lesion that is appropriate for selection as a target lesion per RECIST 1.1 is required prior to patient treatment. Tumor assessment by computed tomography (CT) scan or magnetic resonance imaging (MRI) must be performed within 28 days prior to C1D1.
• All patients enrolled must be ICI-naïve patients defined as no prior exposure to immune-mediated therapy including, but not limited to, other anti CTLA-4, anti-PD-1, anti-PD-L1, and anti-programmed cell death ligand 2 (anti-PD-L2) antibodies, excluding therapeutic anticancer vaccines.
• All patients must be able to provide a tumor tissue either archival tissue or newly acquired tumor biopsy. The tumor specimen should be of sufficient quantity to allow for exploratory biomarker analyses.
• Have adequate organ function as defined in Table 1. Specimens must be collected within 7 days prior to the start of study treatment.

You may not qualify if:

• A WOCBP who has a positive urine pregnancy test within 72 hours prior to allocation (see section 6.4 Pregnancy Testing). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Note: in the event that 72 hours have elapsed between the screening pregnancy test and the first dose of study treatment, another pregnancy test (urine or serum) must be performed and must be negative in order for subject to start receiving study medication.
• Is pregnant or breastfeeding or expecting to conceive within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study treatment.
• Prior/Concurrent Clinical Study Experience:
• \. Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment.
• Note: Patients who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
• Prior/Concomitant Therapy:
• Has received prior therapy with a TGF-β antagonist, IL-15 or analogs.
• Has received prior systemic anti-cancer therapy including investigational agents prior to treatment. Note: Patients must have recovered from all AEs due to previous therapies to ≤Grade 1 or baseline. Patients with ≤Grade 2 neuropathy may be eligible. Note: If patient received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment.
• Has received prior radiotherapy within 2 weeks of start of study treatment. Patients must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-central nervous system (CNS) disease.
• Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed.
• Known severe hypersensitivity (Grade ≥ 3 NCI CTCAE 5.0) to compounds of similar chemical or biologic composition to the investigational product used in the study or any component in its formulations, any history of anaphylaxis, or recent, within 5 months, history of uncontrollable asthma.
• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention.
• Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
• Medical conditions:

Sponsors & Collaborators

• Haider Mahdi: lead
• HCW Biologics: collaborator

MeSH Terms

Conditions

Ovarian Neoplasms

Interventions

Paclitaxel

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Haider S Mahdi, MD

  UPMC Hillman Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: November 22, 2021
• First Posted: December 6, 2021
• Study Start: May 10, 2024
• Primary Completion (Estimated): May 31, 2026
• Study Completion (Estimated): January 31, 2028
• Last Updated: January 1, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share