Administer HCW9218 as monotherapy at assigned dose by SC injection once every 3 weeks. Dose Level

-1 - 0.1 mg/kg

1. - (start) 0.25 mg/kg
2. - 0.5 mg/kg
3. - 0.8 mg/kg
4. - 1.2 mg/kg

HCW9218 at the assigned dose level is administered as a subcutaneous injection once every 3 weeks for a minimum of 2 treatment cycles unless medically contraindicated.

HCW9218

Melissa Geller, MD

This is a single center, Phase I dose finding study of HCW9218 for the treatment of advanced/metastatic solid tumor cancer (except pancreatic and primary brain cancers). HCW9218 is a novel bi-functional fusion protein complex administered by subcutaneous (SC) injection. It is comprised of a soluble fusion of two human TGFβRII domains, human tissue factor, and human IL-15, and a second soluble fusion of two human TGFβRII domains and a sushi domain of human IL-15Rα. HCW9218 activates IL-15R signaling on effector immune cells and the dimeric TGFβRII functions as a "trap" for all three human TGF-β isoforms.

HCW9218 in Select Advanced Solid Tumors

A Phase I Study of HCW9218, a Bifunctional TGF-B; Antagonist/IL-15 Protein Complex, in Select Advanced Solid Tumors After Failing at Least Two Prior Therapies

Given that little to no toxicity is expected, the MTD will be determined using an adaptation of the continual reassessment method (CRM) (O'Quigley, 1996) starting with 1 patient cohorts.

Response rate will be estimated by a simple proportion with 95% confidence limits if sufficient numbers exist

Masonic Cancer Center, University of Minnesota

Neoplasms

All Conditions

Digestive System Diseases

Gland and Hormone Related Diseases

Rare Diseases

Carcinoma

Pancreatic Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Pancreatic Cancer

Camurati-Engelmann Disease

Bifunctional TGF-β antagonist/IL-15 protein complex

Pallavi Chaturvedi

This is a Phase 1b/2, open-label, multi-center, competitive enrollment and dose-escalation study of HCW9218 in patients with advanced/metastatic pancreatic cancer.

The study involves a Phase 1b dose escalation portion with up to 30 patients to determine the MTD using a 3+3 dose escalation design and to designate a dose level for the Phase 2 expansion phase (RP2D).

The Phase 2 portion of the study will consist of an expansion cohort of up to 39 patients receiving HCW9218 monotherapy at the RP2D level. An additional independent Phase 2 cohort of patients receiving HCW9218 at the RP2D level in sequence with gemcitabine and nab-paclitaxel will also be considered.

HCW9218 for Advanced Pancreatic Cancer

A Phase 1b/2 Study of HCW9218, a Bifunctional TGF-β Antagonist/IL-15 Protein Complex, for Advanced Pancreatic Cancer

Evaluate the safety profile (as outlined by incidence of adverse events (AEs) based on CTCAE v5) of HCW9218 monotherapy in subjects with advanced/metastatic pancreatic cancer who have progressed on or are intolerant of standard first-line therapy

Determine the maximum tolerated dose (MTD) and designate the recommended Phase 2 dose level (RP2D) for Phase 2 study of HCW9218 in HCW9218-treated subjects

To evaluate objective response rate (ORR) per RECIST version 1.1

To assess the progression-free survival (PFS) per RECIST version 1.1

OS is defined as the time from first administration of study intervention to the date of death due to any cause.

Duration of response is the time from response to progression or death.

HCW Biologics

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Gonadal Disorders

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Ovarian Cancer

Ovarian Epithelial Cancer

Antineoplastic Agents

All Drugs and Chemicals

Paclitaxel

Carboplatin

Albumin-Bound Paclitaxel

Mitogens

Tubulin Modulators

Antimitotic Agents

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

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

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.

Carboplatin AUC 5 and paclitaxel

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

Kelsey Mitch, RN

Lucia Borasso, RN

Haider S Mahdi, MD

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.

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.

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

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).

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

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

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

The proportion of patients who remain progression-free from the initial date of treatment until 6 months afterwards, with progression defined by RECIST v1.1.Progressive disease (PD) is defined as at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions; appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.

The proportion of patients who remain progression-free from the initial date of treatment until 12 months afterwards, with progression defined by RECIST v1.1.Progressive disease (PD) is defined as at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions; appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.

The proportion of patients who remain progression-free from the initial date of treatment until 18 months afterwards, with progression defined by RECIST v1.1.Progressive disease (PD) is defined as at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions; appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.

Progression-free survival is the median (estimated) time measured from the initial date of treatment to the date of documented progression, or the date of death (in the absence of progression),whichever occurs first, with progression defined by RECIST v 1.1.Progressive disease(PD) is defined as at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions; appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.

The proportion of patients that remain alive from the start of treatment until death from any cause at 6 months.

The proportion of patients that remain alive from the start of treatment until death from any cause at 12 months.

The proportion of patients that remain alive from the start of treatment until death from any cause at 18 months.

The median length of time (estimated) from the start of treatment that patients remain alive, until death from any cause.

Time from first confirmation of response to evidence of disease progression. Progression defined by RECIST v 1.1.Progressive disease(PD) is defined as at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions; appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.

Time from trial enrollment to first documentation of objective response per RECIST v1.1. Complete Response (CR) is defined as disappearance of all target lesions; disappearance of all non-target lesions and normalization of tumor marker level. Partial Response (PR) is defined as at least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD.

The proportion of treated with Complete Response (CR) + Partial Response (PR) + Stable Disease (SD), per RECIST v1.1. Complete Response (CR) is defined as disappearance of all target lesions; disappearance of all non-target lesions and normalization of tumor marker level. Partial Response (PR) is defined as at least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD. Stable Disease (SD) is defined as neither sufficient shrinkage (compared to baseline) to qualify for partial or complete response (CR or PR) nor sufficient increase (taking as reference the smallest sum of diameters at baseline or while on study, whichever is smallest) to qualify for progressive disease (PD).

The proportion of treated patients with Complete Response (CR) + Partial Response (PR), per RECIST v1.1. Complete Response (CR) is defined as disappearance of all target lesions; disappearance of all non-target lesions and normalization of tumor marker level. Partial Response (PR) is defined as at least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD.

Per RECIST v1.1, Stable Disease (SD) is defined as neither sufficient shrinkage (compared to baseline) to qualify for partial or complete response (CR or PR) nor sufficient increase (taking as reference the smallest sum of diameters at baseline or while on study, whichever is smallest) to qualify for progressive disease (PD).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
HCW9218 in Select Advanced Solid Tumors	NCT05322408	Solid Tumor	HCW9218	18 Years -	Masonic Cancer Center, University of Minnesota
HCW9218 for Advanced Pancreatic Cancer	NCT05304936	Advanced Pancre...	HCW9218	18 Years -	HCW Biologics
Antitumor Activity of Neoadjuvant Chemotherapy With or Without HCW9218 in Metastatic Advanced Stage Ovarian Cancer	NCT05145569	Ovarian Cancer	Carboplatin AUC... HCW9218	18 Years -	University of Pittsburgh
Antitumor Activity of Neoadjuvant Chemotherapy With or Without HCW9218 in Metastatic Advanced Stage Ovarian Cancer	NCT05145569	Ovarian Cancer	Carboplatin AUC... HCW9218	18 Years -	University of Pittsburgh
Antitumor Activity of Neoadjuvant Chemotherapy With or Without HCW9218 in Metastatic Advanced Stage Ovarian Cancer	NCT05145569	Ovarian Cancer	Carboplatin AUC... HCW9218	18 Years -	University of Pittsburgh
HCW9218 for Advanced Pancreatic Cancer	NCT05304936	Advanced Pancre...	HCW9218	18 Years -	HCW Biologics

Spots Global Cancer Trial Database for hcw9218

Every month we try and update this database with for hcw9218 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for hcw9218

Every month we try and update this database with for hcw9218 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for hcw9218 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.