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Protocol Details

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

This study is currently recruiting participants.

Summary | Eligibility | Citations | Contacts




Sponsoring Institute

National Cancer Institute (NCI)

Recruitment Detail

Type: Participants currently recruited/enrolled
Gender: Male & Female
Min Age: 18 Years
Max Age: N/A

Referral Letter Required


Population Exclusion(s)

Pregnant Women


Tumor Microenvironment;
Epithelial mesenchymal Transition;

Recruitment Keyword(s)



Advanced Pancreatic Carcinoma

Investigational Drug(s)


Investigational Device(s)



Drug: HCW9218

Supporting Site

National Cancer Institute


Pancreatic cancer has the highest death rate of any solid tumor. It is the fourth most common cause of cancer death in the United States. The 5-year survival rate for people with all stages of pancreatic cancer is less than 10%. Around 80% of pancreatic cancers are not diagnosed until after they have become advanced. These cancers are not curable with chemotherapies. A new approach, called immunotherapy, may show more promise.


To test a study drug (HCW9218) in people with advanced pancreatic cancer.


People aged 18 years and older with advanced pancreatic cancer. The cancer must have progressed despite treatment with chemotherapy; it also must not be eligible for surgery.


Participants will be screened. They will have a physical exam. They will have blood and urine tests and tests of their heart function. They will have imaging scans to measure their tumors.

Participants will receive the study drug (HCW9218) every 28 days as an injection under the skin. They will remain in the treatment center to be monitored for up to 6 hours after the first dose, 3 hours after the second dose, and 30 minutes after subsequent doses.

Participants may also return to the treatment center for additional blood draws throughout the study.

Participants will have their tumors evaluated every 8 weeks to see if the drug is helping them. If it is, they will continue with treatment.

Participants will be followed for up to 3 years. They will have follow-up clinic visits or phone calls every 3 months for the first year and then every 6 months.

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Subjects must meet ALL of the following criteria for inclusion in the study (to be verified by Sponsor prior to subject enrollment):

1. Histologically or cytologically confirmed unresectable, advanced/metastatic disease pancreatic cancer that has progressed on standard first-line (or second- or later line) systemic therapy (excepting progression within 6 months of end of adjuvant systemic chemotherapy); or that can no longer be treated with first-line systemic therapy due to subject s intolerance

2. For dose escalation phase (Phase 1b), distant metastatic disease or advanced disease and not a candidate for down staging to resection

For expansion phase (Phase 2), distant metastatic disease only

3. Measurable disease by CT, MRI, PET-CT or other methods as assessed by RECIST v1.1

4. Prior radiation is allowed if the index lesion(s) remains outside of the treatment field or has progressed since prior treatment. Radiation therapy must have been completed at least 4 weeks prior to the baseline scan.

5. Resolved acute effects of any prior therapy to baseline or Grade <= 1 NCI CTCAE v5.0 except for AEs not constituting a safety risk by Investigator judgment

6. Age >= 18 years

7. Performance status: ECOG performance status of 0, 1 or 2

8. A life expectancy of at least 12 weeks

9. Laboratory tests performed within 14 days of treatment start:

a. Absolute neutrophil count (AGC/ANC) >= 1,500/microliter (>=1.5 X 10^9/L)

b. Platelets >= 100,000/microliter (>= 100 X 10^9/L)

[Subjects may be transfused not more than 1 unit of platelets within 2 weeks to meet this requirement]

c. Hemoglobin >= 9 g/dL (>90g/L)

[Subjects may be transfused not more than 2 units of pRBCs within 2 weeks to meet this requirement]

d. Calculated glomerular filtration rate (GFR)* >40 mL/min OR

serum creatinine <= 1.5 X ULN

e. Total bilirubin <= 2.0 X ULN or <= 3.0 X ULN for subjects with Gilbert's syndrome

f. AST, ALT, ALP <= 2.5 X ULN or <= 5.0 X ULN if liver metastasis present

*using the following Cockcroft & Gault equation to calculate the eGFR for this study. eGFR in mL/min = [(140-age in years) X (weight in kg) X F]/(serum creatinine in mg/dL X72), where F =1 if male; and 0.85 for female.

10. Adequate pulmonary function with PFTs > 50% FEV1 if symptomatic or prior known impairment

11. Negative serum pregnancy test within 14 days of treatment start if female and of childbearing potential (non-childbearing is defined as greater than one year postmenopausal or surgically sterilized)

12. Female subjects of childbearing potential must adhere to using a medically accepted method of birth control prior to screening and agree to continue its use for at least 28 days after the last dose of HCW9218 or be surgically sterilized (e.g., hysterectomy or tubal ligation) and males must agree to use a barrier method of birth control and agree to continue its use for at least 28 days after the last dose of HCW9218

13. Provide signed informed consent and HIPAA authorization and agree to comply with all protocol-specified procedures and follow-up evaluations


Subjects with ANY of the following criteria are excluded from participation in the study (to be verified by Sponsor prior to subject enrollment):

1. History of clinically significant vascular disease, including any of the following within 6 months prior to start of study treatment: MI or unstable angina, percutaneous coronary intervention, bypass grafting, ventricular arrhythmia requiring medication, stroke or transient ischemic attack, symptomatic peripheral arterial disease

2. Marked baseline prolongation of QT/QTc interval (e.g., demonstration of a QTc interval greater than or equal to 470 milliseconds by Fridericia s correction)

3. Subjects with untreated CNS metastases are excluded. Subjects are eligible if CNS metastases are treated and subjects are neurologically stable for at least 2 weeks prior to enrollment. In addition, subjects must be either off corticosteroids, or on a stable or decreasing dose of <= 10 mg daily prednisone (or equivalent)

4. Anti-cancer treatment including surgery, radiotherapy, chemotherapy, other immunotherapy, or investigational therapy within 14 days before treatment start

5. Other prior malignancy except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated Stage I or II cancer from which the subject is currently in complete remission, or any other cancer from which the subject has been disease-free for 3 years after surgical treatment

6. Known hypersensitivity or history of allergic reactions attributed to compounds of similar chemical or biologic composition to the agents used in the study

7. Prior therapy with TGF-Beta antagonist, IL-15 or analogs

8. Concurrent herbal or unconventional therapy (e.g., St. John's Wort)

9. Known autoimmune disease requiring active treatment. Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of enrollment. Inhaled or topical steroids, and adrenal replacement steroid doses <= 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease

10. Active systemic infection requiring parenteral antibiotic therapy. All prior infections must have resolved following optimal therapy.

11. Prior organ allograft or allogeneic transplantation

12. Known HIV-positive or AIDS

13. Women who are pregnant or nursing

14. Any ongoing toxicity from prior anti-cancer treatment that, in the judgment of the Investigator, may interfere with study treatment. All toxicities attributed to prior anti-cancer therapy other than peripheral neuropathy, alopecia, and fatigue must resolve to grade 1 (NCI CTCAE v5.0) or baseline before administration of the study treatment

15. Psychiatric illness/social situations that would limit compliance with study requirements

16. Other illness or a medical issue that in the opinion of the Investigator would exclude the subject from participating in this study

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Not Provided

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Principal Investigator

Referral Contact

For more information:

Christine C. Alewine, M.D.
National Cancer Institute (NCI)
NIHBC 37 BG RM 5116B
(240) 760-6146

NCI Medical Oncology Referral Office
National Cancer Institute (NCI)

(888) 624-1937

NCI Referral Office
National Institute of Health Clinical Center (CC), 9000 Rockville Pike, Bethesda, Maryland 20892, United States: NCI Clinical Trials Referral Office

Clinical Trials Number:


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