Pre-Transplant INCBB099280 for Hepatocellular Carcinoma (HCC)

NCT06337162 | Withdrawn Phase 1 FDA Drug

• 2 other identifiers: UPCC 20223IRB#855195
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This is a pilot safety study of the oral PD-L1 inhibitor INCB099280 in patients with HCC awaiting liver transplant.

Conditions

Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (1)

• Acute Cellular Rejection of Liver Transplant Attributed to Study Therapy

  Proportion of patients who undergo liver transplant who experience biopsy-proven acute cellular rejection of liver transplant using Banff Criteria within 1 month of liver transplantation that is at least possibly related to study therapy

  From liver transplant until 1 month after liver transplant

Secondary Outcomes (7)

• Acute Cellular Rejection of Liver Transplant Within 3 Months

  From liver transplant until 3 months after liver transplant

• Acute Cellular Rejection of Liver Transplant Within 1 Year

  From liver transplant until 1 year after liver transplant

• Toxicity Rates by Category and Grade

  From start of study therapy to 1 month after liver transplant

• Proportion of Patients Downstaged

  From start of study therapy to liver transplant, an average of 6 months

• Pathologic Complete Response Rate

  At time of liver transplant, an average of 6 months

Study Arms (1)

INCB099280

EXPERIMENTAL

Study participants will receive the recommended phase II dose (400mg/kg) of INCB099280 orally on days 1 through 28 of each 28-day cycle until liver transplant.

Drug: INCB099280

Interventions

INCB099280 DRUG

400 mg Tablet

INCB099280

Eligibility Criteria

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

You may qualify if:

• Must have hepatocellular carcinoma (HCC) that is within criteria for liver transplantation per review at multidisciplinary tumor board. This includes HCC tumors meeting downstaging criteria, per United Network for Organ Sharing (UNOS) guidelines.
• Age \> 18 years and ability to understand and the willingness to sign a written informed consent document.
• No prior systemic therapies for HCC
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Child-Pugh cirrhosis score of A5, A6, or B7
• Must be willing to comply with protocol procedures.
• Patients who are undergoing locoregional therapies must have resolution of clinical (i.e. not laboratory) adverse effects associated with the locoregional therapy to grade ≤1 or baseline (whichever is higher).
• Women of childbearing potential must have a negative serum pregnancy test performed within 7 days of the first dose of INCB099280.
• Must have adequate organ and hematopoietic function within 7 days of initiation of study therapy (including Cycle 1 Day 1 labs if needed).

You may not qualify if:

• Any history of a serious medical or psychiatric condition that would prevent the subject from signing the informed consent form.
• Intercurrent illness that might interfere with compliance or study completion.
• Pregnant, expecting to conceive, or breastfeeding starting with the screening visit through 190 days after the last dose of study treatment or expecting to father children starting with the screening visit through 100 days after the last dose of study treatment.
• Subjects may not receive concomitant anticancer agents (except protocol specified INCB099280). Long-term hormonal agents used in the adjuvant setting for other cancers (e.g. tamoxifen for breast cancer, leuprolide for prostate cancer) are permitted.
• Uncontrolled ascites (i.e. requiring paracentesis).
• Hepatic encephalopathy symptoms within 6 months prior to starting study therapy.
• Portal vein invasion or extrahepatic metastatic disease.
• Treatment with non-steroidal systemic immunosuppressive medication within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during study treatment. Systemic agents for skin-only conditions such as atopic dermatitis or psoriasis may be permissible at the discretion of the Principal Investigator.
• Any concurrent condition requiring the continued or anticipated use of systemic steroids beyond physiologic replacement dosing (excluding non-systemic inhaled, topical skin, nasal, and/or ophthalmic corticosteroids). All other systemic corticosteroids above physiologic replacement dosing must be discontinued at least 2 weeks prior to first study treatment. Patients who receive a corticosteroid pulse for IV contrast allergies are eligible.
• Active drug or alcohol use or dependence as documented in the chart that, in the opinion of the investigator, would interfere with adherence to study requirements or interfere with eligibility for liver transplantation.
• Serious active bacterial or fungal infection requiring oral or intravenous antibiotics or antifungals at the start of protocol treatment. Participants may enroll after a 28-day washout period. Prophylactic or suppressive antibiotics (e.g. for spontaneous bacterial peritonitis prophylaxis, dental procedures, or surgical prophylaxis) are allowed.
• A second primary malignancy that, in the judgment of the investigator, may affect the interpretation of results and/or eligibility for liver transplantation. Exceptions may be made if the participant has undergone potentially curative therapy with no evidence of disease recurrence for 3 years since initiation of that therapy and the participant is otherwise a candidate for Liver Transplant (Note: The time requirement for no evidence of disease for 3 years does not apply to participants who underwent successful definitive resection of basal cell carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma of the skin, in situ cervical cancer, other noninvasive or indolent malignancies, or other in situ cancers if the presence or history of these cancers would not otherwise affect candidacy for liver transplant (LT)).
• Prior organ allograft or allogeneic bone marrow transplantation.
• Active autoimmune disease, except for vitiligo, type 1 diabetes mellitus, asthma, atopic dermatitis, psoriasis, or endocrinopathies manageable by hormone replacement; other autoimmune conditions with low risk of complications due to Immune Checkpoint Inhibitors (ICI) use may be allowable at the discretion of the Principal Investigator.
• Any other conditions judged by the investigator that would limit the evaluation of the subject.

Sponsors & Collaborators

• Abramson Cancer Center at Penn Medicine: lead
• Incyte Corporation: collaborator

Study Sites (1)

Abramson Cancer Center at University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Study Officials

• Thomas Karasic, MD

  Abramson Cancer Center at the University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 18, 2024
• First Posted: March 29, 2024
• Study Start: May 1, 2024
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): September 1, 2028
• Last Updated: August 9, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)