A Study Evaluating the Safety and Efficacy of HB0036 in Subjects With Advanced Solid Tumors

NCT05417321 | Recruiting Phase 1 FDA Drug

• 1 other identifier: HB0036-01
• Study Type: interventional
• Target: 80
• Locations: 2 countries
• Sites: 4

Brief Summary

It is a Phase I/II, Open-label, Multicenter Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of HB0036 in Subjects with Advanced Solid Tumors

Conditions

Advanced Solid Tumor; NSCLC

Outcome Measures

Primary Outcomes (2)

• Safety and tolerability

  Number of participants with a Dose Limiting Toxicity (DLT) \[ Time Frame: During the first 21 days \]DLTs will be assessed during the first 21 days of treatment for dose-escalation phase and are defined as toxicities that meet pre-defined severity criteria, and assessed as having a suspected or definite relationship to study drug.

  Up to 12 Months

• MTD

  MTD or OBD and/or RP2D.

  Up to 24 Months

Secondary Outcomes (3)

• AUC

  Up to 24 Months

• Cmax

  Up to 24 Months

• Tmax

  Up to 24 Months

Other Outcomes (1)

• ORR assessment in dose-escalation phase

  Up to 24 Months

Study Arms (1)

HB0036

EXPERIMENTAL

HB0036 IV every 3 weeks (q3w)

Drug: HB0036

Interventions

HB0036 DRUG

Patients will be assigned to dose regimens in the order of enrollment, and they will receive their assigned fixed dose of HB0036 via intravenous infusion. HB0036 IV every 3 weeks (q3w).

Also known as: Anti-PD-L1 and anti-TIGIT bifunctional molecule

HB0036

Eligibility Criteria

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

You may qualify if:

• Patients must meet all the following criteria to be eligible for participation in this study:
• Male or female. Age ≥ 18 years;
• Phase I: Patients with histologically or cytologically confirmed locally advanced, recurrent, or metastatic solid tumors (or clinically diagnosed hepatocellular carcinoma) that failed all standard therapies known to provide clinical benefit; \[These solid tumors include but not limit to: non-small cell lung cancer, esophageal squamous cell carcinoma, melanoma, head and neck squamous cell carcinomas, hepatocellular carcinoma, gastric or gastroesophageal junction adenocarcinoma, renal cell carcinoma, etc.\];
• Phase II: Histologically or cytologically documented locally advanced, recurrent or metastatic cancer. There will be several tumor-specific cohorts Advanced non-small cell lung cancer cohort Histologically or cytologically documented locally advanced, recurrent or metastatic NSCLC; Confirmed availability of representative tumor specimens in formalin-fixed paraffin-embedded (FFPE）blocks or at least 5 stained serial slides or fresh biopsied specimens (preferred),samples obtained before adjuvant / neoadjuvant chemotherapy are allowed only if biopsy cannot be performed; Tumor PD-L1 expression with a TPS≥1 %; Negative for actionable molecular markers \[including but not limited to: epidermal growth factor receptor (EGFR) mutations, anaplastic lymphoma kinase (ALK) gene fusion mutation, etc.\]； Assessed by the investigator as likely to benefit from the study drug therapy; and should have progressed at least one prior systemic therapy regimen.
• Advanced other cancer cohort Histologically or cytologically documented locally advanced, recurrent or metastatic cancer (esophageal squamous cell carcinoma, melanoma) Other tumor histologies will be evaluated pending data from the dose escalation phase that may inform on possible efficacy in select tumors
• At least one measurable lesion( assessable lesion only accepted during accelerated titration stage) as per RECIST v. 1.1 defined as non-nodal lesions having at least one dimension with a minimum size of 10 mm in the longest diameter by CT or MRI scan or ≥15 mm in short axis for nodal lesions. Radiographic disease assessment at baseline can be performed up to 21 days prior to the first dose.
• Note: Tumour lesions situated in a previously irradiated area, or in an area subjected to other loco-regional therapy, are not considered measurable unless there has been demonstrated progression in the lesion.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-1
• Life expectancy ≥12 weeks
• Adequate organ function within 14 days of the first dose as defined by the following criteria:
• a) Hematology
• absolute neutrophil count (ANC) ≥ 1.5×109/L;
• ② platelets (PLT) ≥ 75×109/L;
• ③ hemoglobin (HGB) ≥ 90 g/L; Note: The above three items require that patients should not have received any blood component or cell growth factor supportive therapy within two weeks prior to blood sampling.
• b) Renal function: Calculated creatinine clearance (CrCL) \> 50 mL/min (Cockroft-Gault Equation); c) Liver function:

You may not qualify if:

• Patients are excluded from the study if any of the following criteria apply:
• Concurrent malignancy \< 5 years prior to entry other than adequately treated cervical carcinoma-in-situ, localized squamous cell cancer of the skin, basal cell carcinoma, localized prostate cancer, ductal carcinoma in situ of the breast, or \< T1 urothelial carcinoma. Patients with prostate cancer that is under active surveillance are eligible.
• Phase I: Patients may have received single agent treatments targeting the TIGIT pathway.
• Phase II: Have received previous simultaneous therapy with a PD-1 pathway inhibitor and a TIGIT inhibitor; previous monotherapy with TIGIT/PD-1/PD-L1 inhibitor is allowed.
• Have received antibiotics lasting over 1 week within 28 days prior to first dose;
• Have clinically active central nervous system (CNS) metastases and/or carcinomatous meningitis. Patients with previously-treated brain or meningeal metastases may participate and be eligible for treatment provided they are stable and asymptomatic. Patients with asymptomatic brain metastasis or subjects who are symptomatically stable after treatment and are on \< 10 mg/d prednisone or equivalent are eligible.
• Have history of interstitial lung disease or non-infectious pneumonitis (except from radiotherapy);
• Active autoimmune disease or history of autoimmune disease requiring systemic therapy \< 2 years prior to screening except hypothyroidism, vitiligo, Grave's disease, Hashimoto's disease, or Type I diabetes. Patients with childhood asthma or atopy that has not been active in the 2 years prior to study screening are eligible.
• History of Grade 3-4 immune-related adverse events (irAEs) or irAEs requiring discontinuation of prior therapies, (except for grade 3 endocrinopathy that is managed with hormone replacement therapy).
• Use of systemic corticosteroids in a dose equivalent to \>10 mg/day of prednisone or other immunosuppressive agent \< 2 weeks prior to screening; the use of topical, intraocular, intraarticular, intranasal, or inhaled corticosteroids and systemic steroids to prevent (e.g., allergy to contrast agents) or treat non-autoimmune condition (e.g., delayed hypersensitivity caused by exposure to allergens) or short course (\< 5 days) will be allowed
• Anticancer therapy or radiation \< 5 half-lives or 4 weeks (whichever is shorter) prior to study entry; palliative radiotherapy to a single area \< 2 weeks prior to study screening is permitted. Measurable lesions cannot be previously irradiated unless they have demonstrated growth after radiation therapy (RT).
• Major surgery (except for diagnostic needle biopsy or intravenous catheterization) or chemotherapy/ interventional therapy/radiation therapy/ablation therapy \< 4 weeks prior to the first dose;
• Cerebrovascular accident (CVA), transient ischemic attack (TIA), myocardial infarction (MI), unstable angina, or New York Heart Association (NYHA) class III or IV heart failure \< 6 months of study entry; mean ECG QT-interval corrected according to Fridericia's formula (QTcF) \> 470 milliseconds (ms) obtained from three ECGs; uncontrolled arrhythmia \< 3 months of study entry. Patients with rate-controlled arrhythmias may be eligible for study entry at discretion of the Investigator.
• Patients who have previously received allogeneic stem cell or solid organ transplantation.
• Have received or will receive a live vaccine within 4 weeks prior to the first dose, except COVID-19 vaccine.

Sponsors & Collaborators

• Shanghai Huaota Biopharmaceutical Co., Ltd.: lead

Study Sites (4)

Horizon Oncology

Lafayette, Indiana, 47905, United States

RECRUITING

Next Oncology

San Antonio, Texas, 78229, United States

RECRUITING

Summit Cancer Centers

Spokane, Washington, 99216, United States

RECRUITING

Shandong Hospital

Jinan, Shandong, 250117, China

RECRUITING

Study Officials

• Yang Yang, MD/PHD

  Shanghai Huaota Biopharmaceutical Co., Ltd.

  STUDY DIRECTOR

Central Study Contacts

Jingjing Wang, Master

CONTACT

021-51320053; jingjing.wang@huaota.com

Yang Zheng, MD

CONTACT

021-51320053; yang.zheng@huaota.com

Study Design

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

Model Details: A single-subject cohort will be enrolled at the protocol starting dose of HB0036 every 3 weeks (Q3W). Dose escalation will proceed to the next main dose level according to the 3+3 dose-escalation procedure until the MTD/OBD is reached. Phase II of the study will be initiated at the Sponsor's discretion at the dose level and treatment schedule which was established as the recommended Phase 2 dose (RP2D) in the dose-escalation phase.

Study Record Dates

• First Submitted: May 30, 2022
• First Posted: June 14, 2022
• Study Start: August 25, 2022
• Primary Completion: August 1, 2025
• Study Completion: August 1, 2025
• Last Updated: January 3, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1); US (3)