Trial Title:
BC3402 w/ Tremelimumab + Durvalumab (STRIDE) in Hepatocellular Carcinoma
NCT ID:
NCT06608940
Condition:
Hepato Cellular Carcinoma (HCC)
Conditions: Official terms:
Carcinoma
Carcinoma, Hepatocellular
Durvalumab
Tremelimumab
Conditions: Keywords:
liver cancer
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
BC3402
Description:
BC3402, intravenous, 20 mg/kg, D1 and D15 of every 28 day cycle, continuous. BC3402 to be
administered after completion of the infusion of durvalumab and/or tremelimumab on the
days when BC3402 is to be administered with durvalumab and/or tremelimumab
Arm group label:
BC3402 to tremelimumab plus durvalumab
Intervention type:
Drug
Intervention name:
Durvalumab
Description:
Durvalumab, intravenous, 1500 mg, every 4 weeks, continuous
Arm group label:
BC3402 to tremelimumab plus durvalumab
Intervention type:
Drug
Intervention name:
Tremelimumab
Description:
Tremelimumab, intravenous, 300 mg, 1 dose on Cycle 1 Day 1
Arm group label:
BC3402 to tremelimumab plus durvalumab
Summary:
The purpose of this study is to test the safety and efficacy of an investigational
(experimental) product called BC3402. This product is considered experimental because it
is not approved by the U.S. Food and Drug Administration (FDA).
Detailed description:
Brief Background/Rationale
Hepatocellular carcinoma (HCC) is the most common liver cancer and the fastest rising
cause of cancer-related deaths in the U.S. Immune checkpoint inhibitors (ICIs) proved to
be highly efficacious in HCC and the dual ICIs combination, tremelimumab plus durvalumab,
is a standard front-line treatment for advanced and metastatic HCC. However, the response
rate of the dual ICIs regimen is about 20% and participants invariably progress. There is
a need for more efficacious treatment.
T cell immunoglobulin mucin-3 (TIM3) is highly expressed on multiple immune cells and
plays a complex role in regulating immune responses and inducing immune tolerance. BC3402
is a TIM3 targeting inhibitory humanized IgG4 subtype monoclonal antibody which displays
synergistic anti-tumor effects when combined with agents targeting PD1 and CTLA4 in
preclinical tumor models as well as in the first in human (FIH) trial. Investigators
hypothesize that the co-targeting of TIM3 will significantly increase the anti-tumor
efficacy of dual targeting of PD1/PDL1 and CTLA4 axes in HCC and thus propose a clinical
trial to investigate the efficacy of a novel triplet ICI combination of BC3402 plus the
STRIDE regimen in participants with advanced, unresectable treatment-naïve HCC.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Written informed consent and any locally required authorization (eg, Health
Insurance Portability and Accountability Act in the US, European Union [EU] Data
Privacy Directive in the EU) obtained from the participant/legal representative
prior to performing any protocol-related procedures, including screening
evaluations.
- Confirmed HCC based on histopathological findings from tumor tissue.
- Must not have received prior systemic therapy for advanced, non-resectable HCC.
- Must not be eligible for locoregional therapy for unresectable HCC. For participants
who progressed after locoregional therapy for HCC, locoregional therapy(including
Transarterial chemoembolization (TACE) or Transarterial radioembolization (TARE))
must have been completed ≥28 days prior to the baseline scan for the current study.
- Barcelona Clinic Liver Cancer (BCLC) stage B (that is not eligible for locoregional
therapy) or stage C.
- Child-Pugh Score class A.
- The Eastern Cooperative Oncology Group(ECOG) performance status of 0 or 1 at
enrollment.
- Participants with Hepatitis B virus infection (as characterized by positive
hepatitis B surface antigen [HBsAg], detectable HBV DNA, or hepatitis B core
antibodies [anti-HBc Ab]) and are eligible for inclusion must be treated with
antiviral therapy, per institutional practice, to ensure adequate viral suppression
(HBV DNA ≤2000 IU/mL) prior to enrollment.
o Note: HBV-positive participants must remain on antiviral therapy for the study
duration and must continue therapy for 6 months after the last dose of study
medication.
- Participants with Hepatitis C virus infection that are otherwise eligible for
inclusion, must be confirmed by the presence of detectable HCV RNA or anti-HCV
antibody upon enrollment (management of this disease is per local institutional
practice).
- At least 1 measurable lesion, not previously irradiated and/or embolized, that can
be accurately measured at baseline as ≥10 mm in the longest diameter (except lymph
nodes, which must have a short axis ≥15 mm) with CT or MRI, and that is suitable for
accurate repeated measurements as per RECIST 1.1 guidelines.
- Adequate organ and marrow function, as defined below. Criteria "a," "b," "c," and
"f" cannot be met with transfusions, infusions, or growth factor support
administered within 14 days of starting the first dose.
1. Hemoglobin ≥9 g/dL
2. Absolute neutrophil count ≥1000/μL
3. Platelet count ≥75000/μL
4. Total bilirubin (TBL) ≤2.0×ULN
5. AST and ALT ≤5×ULN
6. Albumin ≥2.8 g/dL
7. International normalized ratio (INR) ≤1.6
8. Calculated creatinine clearance ≥45 mL/minute as determined by Cockcroft-Gault
(using actual body weight) or 24-hour urine creatinine clearance
- Evidence of post-menopausal status or negative urinary or serum pregnancy test for
female pre-menopausal participants.
- Must have body weight <100kg to be enrolled at the 20mg/kg dose level.
Exclusion Criteria:
- Any unresolved toxicity National Cancer Institute (NCI) Common Terminology Criteria
for Adverse Event (CTCAE) Grade ≥2 from previous anticancer therapy with the
exception of alopecia, vitiligo, and the laboratory values defined in the inclusion
criteria:
- Participants with Grade ≥2 neuropathy will be evaluated on a case-by-case basis
after consultation with the Study Physician.
- Participants with irreversible toxicity not reasonably expected to be exacerbated by
treatment with durvalumab or tremelimumab may be included only after consultation
with the Study Chair.
- Have received an investigational product or locoregional therapy within 28 days
prior to the first dose of study drug(s).
- Any concurrent chemotherapy, study drug, or biologic or hormonal therapy for cancer
treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (eg,
hormone replacement therapy) is acceptable.
- Known allergy or hypersensitivity to any of the study drugs or any of the study drug
excipients.
- Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of
radiation within 28 days of the first dose of study drug(s).
- Major surgical procedure (as defined by the Investigator) within 28 days prior to
the first dose of study drug(s). Note: Local surgery of isolated lesions for
palliative intent is acceptable.
- History of allogeneic organ transplantation (eg, liver transplant).
- History of hepatic encephalopathy within past 12 months or requirement for
medications to prevent or control encephalopathy (eg, no lactulose, rifaximin, etc
if used for purposes of hepatic encephalopathy).
- Ascites that require ongoing paracentesis, within 6 weeks prior to the first
scheduled dose of study drug(s), to control symptoms.
- Main portal vein thrombosis present on imaging.
- Active or prior documented GI variceal bleed or history of upper GI bleeding,
ulcers, or esophageal varices with bleeding within 12 months; adequate endoscopic
therapy according to institutional standards is required for participants with
history of esophageal variceal bleeding or assessed as high risk for esophageal
variceal by the treating investigator.
- Participant currently exhibits symptomatic or uncontrolled hypertension defined as
diastolic blood pressure >90 mmHg or systolic blood pressure >140 mmHg.
- Active or prior documented autoimmune or inflammatory disorders (including
inflammatory bowel disease [eg, colitis or Crohn's disease], diverticulitis
[with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis
syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves'
disease, rheumatoid arthritis, hypophysitis, uveitis, etc]). Participants without
active disease in the last 5 years are excluded unless discussed with the Study
Physician and considered appropriate for study participation. The following are
exceptions to this criterion:
- Participants with vitiligo or alopecia
- Participants with hypothyroidism (eg, following Hashimoto syndrome) stable on
hormone replacement
- Any chronic skin condition that does not require systemic therapy
- Participants with celiac disease controlled by diet alone
- Confirmed HBV infection must not be co-infected with HCV (as indicated by the
absence of anti-HCV antibodies).
- Confirmed HCV infection must not be co-infected with HBV as defined by negative
HBsAg. Participants with confirmed HCV infection who are negative for HBsAg, but
positive for anti-HBc with detectable HBV DNA, are eligible but must be started on
active antiviral therapy (for HBV) prior to enrollment to ensure adequate viral
suppression (HBV DNA ≤2000 IU/mL).
- Uncontrolled intercurrent illness, including but not limited to, ongoing or active
infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable
angina pectoris, cardiac arrhythmia, Interstitial lung disease (ILD), serious
chronic GI conditions associated with diarrhea, or psychiatric illness/social
situations that would limit compliance with study requirement, substantially
increase the risk of incurring AEs, or compromise the ability of the participant to
give written informed consent.
- History of another primary malignancy except for:
- Malignancy treated with curative intent and with no known active disease ≥5 years
before the first dose of study drug(s) and of low potential risk for recurrence
- Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of
disease
- Adequately treated carcinoma in situ without evidence of disease
- History of leptomeningeal carcinomatosis.
- Brain metastases or spinal cord compression. Participants with suspected brain
metastases at screening should have an MRI (preferred) or CT, each preferably with
IV contrast of the brain prior to study entry.
- Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC.
- History of active primary immunodeficiency.
- Active infection including tuberculosis (TB) (clinical evaluation that includes
clinical history, physical examination and radiographic findings, and TB testing in
line with local practice), or human immunodeficiency virus (positive human HIV 1/2
antibodies).
- Current or prior use of immunosuppressive medication within 14 days before the first
dose of study drug(s). The following are exceptions to this criterion:
- Intranasal, inhaled, topical steroids, or local steroid injections (eg,
intra-articular injection)
- Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone
or its equivalent
- Steroids as premedication for hypersensitivity reactions (eg, CT scan premedication)
- Receipt of live attenuated vaccine within 30 days prior to the first dose of study
drug(s). Note: Participants, if enrolled, should not receive live vaccine while
receiving study drug(s) and up to 30 days after the last dose of study drug(s).
- Female participants who are pregnant or breastfeeding or male or female participants
of reproductive potential who are not willing to employ effective birth control from
screening to 90 days after the last dose of durvalumab monotherapy or 180 days after
the last dose of durvalumab plus tremelimumab combination therapy. Not engaging in
sexual activity, as per the participant's preferred and usual lifestyle, for the
total duration of the treatment and washout periods is an acceptable practice.
- Prior randomization or treatment in a previous durvalumab and/or tremelimumab
clinical study regardless of treatment arm assignment.
- Participants who have received anti-PD-1, anti PD-L1, or anti CTLA-4 prior to the
first dose of study drug(s)
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Case Comprehensive Cancer Center Cleveland Clinic Taussig Cancer Center
Address:
City:
Cleveland
Zip:
44195
Country:
United States
Contact:
Last name:
Wen Wee Ma, MBBS
Start date:
December 1, 2024
Completion date:
January 1, 2028
Lead sponsor:
Agency:
Case Comprehensive Cancer Center
Agency class:
Other
Source:
Case Comprehensive Cancer Center
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06608940
