Clinical trial NCT06771622: Safety and Efficacy of HCB101 in Combination With Multiple Agents in Patients With Advanced Solid Tumors
Official title: Phase Ib/IIa, Open-label, Multicenter, Dose Escalation, and Dose Expansion Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Antitumor Activity of HCB101 in Combination With Multiple Agents in Subjects With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Solid Cancer
Lead sponsor: FBD Biologics Limited
Sponsor class: INDUSTRY
First posted: 2025-01-13
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a non-randomized, open-label, dose-escalation, and dose-expansion Phase Ib/IIa study to evaluate the safety, tolerability, PK profile, and preliminary efficacy of HCB101 in combination therapies in subjects with advanced solid tumors. The trial consists of four cohorts, each including a part I of the dose-escalation phase (Phase Ib) and a part II of the dose-expansion phase (Phase IIa).


Eligibility criteria: Inclusion Criteria:

1. Subjects are able to understand and willing to provide signed informed consent.
2. Male and female subjects of ≥18 years of age, inclusive, at the time of signing the informed consent.
3. With histologically/cytologically confirmed diagnosis of advanced solid tumors as described below:

   1. Cohort 1: HER2 overexpression positive (IHC 3+ or IHC 2+ and evidence of HER2 amplification by FISH), unresectable locally advanced, recurrent, or metastatic gastric cancer, patients must be previously untreated with systemic treatment; Subject that received neoadjuvant chemotherapy with recurrence \>6 months from completion of therapy are permitted.
   2. Cohort 2: Unresectable locally advanced, recurrent, or metastatic gastric cancer, progression on or after first-line standard treatment; Prior neoadjuvant or adjuvant therapy can be counted as a line of therapy if the subject progressed on or within 6 months of completing neoadjuvant or adjuvant therapy.
   3. Cohort 3: Advanced or metastatic colorectal cancer, RAS (KRAS, NRAS) gene is wild-type, and no BRAF V600E mutation has been identified, progression on or after first-line standard treatment; Prior neoadjuvant or adjuvant therapy can be counted as a line of therapy if the subject progressed on or within 6 months of completing neoadjuvant or adjuvant therapy.
   4. Cohort 4: Recurrent unresectable (local or regional) or stage IV (M1) triple-negative breast cancer TNBC, whose tumors express PD-L1 with a CPS ≥ 10, patients must be previously untreated with systemic treatment; Subject that received neoadjuvant chemotherapy with recurrence \>6 months from completion of therapy are permitted.
4. Have adequate organ function, as indicated by the following laboratory parameters below (had not received a blood transfusion, apheresis infusion, erythropoietin, granulocyte colony-stimulating factor, and other relevant medical support within 14 days before the administration of the first dose of study intervention).

Exclusion Criteria:

1. With a known history of hypersensitivity to any components of the study intervention.
2. Subjects who have other malignancies requiring treatment within 2 years before the first dose of study intervention will be excluded, except for radically treated locally curable basal or squamous cell skin cancer and other malignancies that have been treated with no relapse within 2 years.
3. Subjects who have undergone any investigational or approved systemic cancer therapy (including chemotherapy, immunotherapy, hormonal therapy, and herbal/alternative therapies with anti-cancer indications or targeted therapy) within 14 days or 5 half-lives, whichever is longer, before the first dose of the study intervention.
4. Subjects who have received any treatment targeting the CD47 or SIRPα pathway.
5. An uncontrolled acute infection.
6. Known to have a history of alcoholism or drug abuse.
7. Any other medical (e.g., Child-Pugh class B or C, pulmonary, metabolic, congenital, endocrinal or CNS disease, etc.), psychiatric, or social condition deemed by the Investigator to be likely to interfere with a subject's rights, safety, welfare or ability to sign informed consent, cooperate and participate in the study, or interfere with the interpretation of the results.

Primary outcomes:
measure: Number/incidence and percentage of subjects with adverse events.
timeFrame: 12 months
measure: Number of subjects with Maximal tolerance dose (MTD) of HCB101
timeFrame: 12 months
Secondary outcomes:
measure: Overall Rate Response (ORR)
timeFrame: 12 months
measure: Duration of Response (DoR)
timeFrame: 12 months
measure: Disease Control Rate (DCR)
timeFrame: 12 months
measure: Progression-Free Survival (PFS)
timeFrame: 12 months
measure: Peak Plasma Concentration (Cmax) of HCB101
timeFrame: 12 months
measure: Area under the plasma concentration versus time curve (AUC) of HCB101
timeFrame: 12 months
measure: Time to maximum drug concentration in plasma (Tmax) of HCB101
timeFrame: 12 months
measure: Terminal elimination half-life (t1/2) of HCB101
timeFrame: 12 months
Other outcomes:
Locations:
city: Jinan
country: China
facility: Cancer Hospital of Shandong First Medical University
state: Shandong
Study officials:
References: