A Study of BH009 in Head and Neck Squamous Cell Carcinoma and Ovarian Cancer

A Phase I Study To Evaluate The Safety, Tolerability and Pharmacokinetics Of BH009 In Patients With Advanced Head And Neck Squamous (Non-nasopharyngeal) And Ovarian Cancer

This study will assess the safety and tolerability and pharmacokinetics of BH009 in patients with advanced head and neck squamous (non-nasopharyngeal) and ovarian cancer.

Study Overview

• Status: Recruiting
• Conditions: Solid Tumor, Adult
• Intervention / Treatment: Drug: BH009

Detailed Description

This is a multicenter, open label phase I clinical study to evaluate the safety, tolerability, and pharmacokinetic profile of BH009 in patients with advanced squamous head and neck cancer (non-nasopharyngeal) and ovarian cancer, and to initially explore its clinical effectiveness. This study will use a "3+3" dose escalation design to determine the maximum tolerated dose (MTD) and the recommended phase 2 dose (RP2D) of BH009.

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Xiaohua Wei, PM; Phone Number: 13500248359; Email: xhwei@bayhibiotech.com
• Study Contact Backup: Name: Mingyue Zeng, APM; Phone Number: 15113340590; Email: myzeng@bayhibiotech.com

Study Locations

• China
  • Anhui
    • Bengbu, Anhui, China
      • Recruiting
      • The First Affiliated Hospital of Bengbu Medical University
      • Contact: YuZhi Li, PI; Phone Number: 13955256571; Email: liyuzhi0518@sina.com
      • Contact: Huan Zhou, PI; Phone Number: 13665527160; Email: zhouhuanbest@vip.163.com
  • Guangdong
    • Guangzhou, Guangdong, China
      • Recruiting
      • The First Affiliated Hospital, Sun Yat-sen University
      • Contact: Shuzhong Yao, PI; Phone Number: 13602834127; Email: zsyyyb@mail.sysu.edu.cn
  • Hunan
    • Changsha, Hunan, China
      • Recruiting
      • Hunan Cancer Hospital
      • Contact: Jing Wang, PI; Phone Number: 13875902083; Email: wangjing189@163.com
      • Contact: Ya Han, PI; Phone Number: 18673176667; Email: hanyaqiancs@163.com
  • Liaoning
    • Dalian, Liaoning, China
      • Recruiting
      • Affiliated Zhongshan Hospital of Dalian University
      • Contact: Xiang Li, PI; Phone Number: 18018931093; Email: 94207842@qq.com
  • Shanghai
    • Shanghai, Shanghai, China
      • Recruiting
      • Obstetrics & Gynecology Hospital of Fudan University
      • Contact: Yu Kang; Phone Number: 13636328211; Email: kangyu1489@fckyy.org.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or female subjects aged between 18-70 years old at the time of informed consent.
2. Histologically or cytologically proven squamous cell carcinoma of the head and neck(including oropharynx, oral cavity, hypopharynx and larynx, excluding nasopharyngeal carcinoma) and ovarian carcinoma (including epithelial ovarian carcinoma, fallopian tube carcinoma and primary peritoneal carcinoma).
3. Subjects who failed by standard treatments, or refused standard treatments, or the investigator considered the subject unsuitable for standard treatments.
4. At least one measurable lesion according to RECIST 1.1 at baseline.
5. Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
6. Subjects must have an expected survival of at least 3 months.

7. Subjects must have adequate organ and marrow function. Laboratory results meet the following conditions within 7 days prior to the first dose [subjects must not have received recombinant granulocyte-colony stimulating factor (G-CSF) or blood transfusion within 14 days prior to the first dose]:

   • Hematological : Absolute neutrophil count(ANC)≥1.5×109/L, platelet count(PLT)≥100×109/L, hemoglobin(Hb)≥90 g/L;
   • Renal function :Serum creatinine(Cr)≤1.5×ULN and creatinine Clearance ≥50 mL/min(Cockcroft-Gault );
   • Liver function : Total bilirubin ≤1.5×ULN, alanine aminotransferase(ALT)and aspartate aminotransferase(AST) ≤ 1.5×ULN (if liver tumor/metastases are present, then ≤2.5×ULN is allowed).
8. Subjects with a left ventricular ejection fraction of ≥50% measured by echocardiography at baseline, a normal 12-lead electrocardiogram or no clinically significant abnormalities, QTc intervals <450 ms (men) or <470 ms (women) (Fridericia's), and no signs or symptoms of heart failure.
9. Subjects with remission of toxicity due to prior therapy to ≤ grade 1 (except for toxicities such as alopecia that are not considered a safety risk by investigator).
10. Subjects have not received surgery, chemotherapy, radiotherapy, immunotherapy, biotherapy, targeted therapy, anti-tumour herbs, small molecule targeted drugs, within 4 weeks or 5 half-lives (whichever is shorter) prior to the first dose of the drug.
11. Subjects voluntarily signed the informed consent form, had good compliance, were available for follow-up, and voluntarily complied with study regulations.

Exclusion Criteria:

1. Subjects with a known hypersensitivity to the study drug and any excipient contained in the drug formulation,or intolerance to paclitaxel analogues.
2. Subjects are currently receiving other anti-tumor therapy.
3. Subjects requiring a potent inhibitor of CYP3A4 within 14 days prior to the first dose and during the study period.
4. Subjects have been treated with systemically administered glucocorticosteroid (prednisone > 10 mg/day or equivalent dose of other similar drug) or other immunosuppressive agents within 14 days prior to the first use of the investigational medicinal product; with the exception of the following: treatment with topical, ophthalmic, intra-articular, intranasal, and inhaled glucocorticosteroids; and short-term prophylactic glucocorticosteroids (e.g., prevention of allergy to contrast media).
5. Subjects with clinically significant psychiatric or central nervous system disorders.
6. Subjects with a primary malignant tumour of the brain; or those who with two or more malignant tumours (except cured non-melanoma skin cancer, cervical cancer, thyroid cancer and intramucosal cancer of the gastrointestinal tract).

7. Subjects who with serious medical conditions:

   • Subjects with clinically significant cardiovascular disease, including: severe or uncontrolled heart disease requiring treatment, congestive heart failure classified by the New York Heart Association (NYHA) as grade 3 or 4, unstable angina pectoris uncontrolled by medication, history of myocardial infarction within 6 months prior to enrolment, severe arrhythmia requiring medication (except atrial fibrillation or paroxysmal supraventricular tachycardia);
   • Subjects with indwelling cardiac stents within 6 months;
   • Subjects with uncontrolled hypertension (systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥100 mmHg after pharmacological intervention), diabetes mellitus (glycated haemoglobin HbA1c ≥8.0% or fasting blood glucose ≥10.0 mmol/L), pleural effusion, pericardial effusion, ascites;
   • Subjects have uncontrolled peptic ulcer, or other uncontrolled thromboembolic event;
   • Subjects with interstitial lung disease, pulmonary fibrosis, or a history of pneumonia requiring steroid therapy.
8. Subjects with known HIV, HBV, HCV, and syphilis spirochete infections (hepatitis B surface antigen (HBsAg)-positive with HBV-DNA greater than 1,000 IU/mL; HCV-Ab-positive with a copy number higher than the upper limit of normal on the HCV RNA assay); and uncontrolled active infections (in those requiring systemic anti-infective therapy, or subjects with a temperature of >38°C (axillary temperature) prior to dosing and unable to explain it).
9. Subjects have a history of drug abuse.
10. Pregnant or nursing women; positive pregnancy test within 7 days prior to the first dose in female subjects of childbearing potential; any female subjects of childbearing potential does not consent to use of a medically recognised effective method of contraception throughout the trial period and for 3 months after the the last dose.
11. Subjects who have been participated in other clinical trial within 28 days prior to the first dose (from the date of the last dose).
12. Subjects who have been vaccinated within 28 days prior to the first dose or who will be vaccinated throughout the study (except for inactivated vaccines).
13. Subjects who be unsuitable for inclusion by investigators judgement.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BH009; Every 28 days constitutes a treatment cycle, and administration on day 1, day 8, day 15 of each cycle	Drug: BH009; Every 28 days constitutes a treatment cycle, and administration on day 1, day 8, day 15 of each cycle

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]	All adverse events (AE) defined by CTCAE version 5.0	first dose to 30 days after last dose
Recommended phase 2 dose of BH009	defined by CTCAE version 5.0	first dose to 30 days after last dose
MTD of BH009	When the dose is incremented beyond the MTD, the previous lower dose group will be identified as the MTD.	first dose to 30 days after last dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate	Objective response rate by RECIST version 1.1	After first dose until 30 days after last dose
Duration of relief	Duration of relief by RECIST version 1.1	After first dose until 30 days after last dose
Disease control rate	Disease control rate by RECIST version 1.1	After first dose until 30 days after last dose
Progression-free survival	Disease control rate by RECIST version 1.1	After first dose until 30 days after last dose
PK Analysis of BH009	Maximum Concentration (Cmax)	predose, 30 minutes, 45 minutes, 1 hour after the start of infusion (immediately after the end of infusion), 5 minutes, 15 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 24 hours, and 48 hours after the end of infusion
PK Analysis of BH009	Time to Cmax (Tmax)	predose, 30 minutes, 45 minutes, 1 hour after the start of infusion (immediately after the end of infusion), 5 minutes, 15 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 24 hours, and 48 hours after the end of infusion
PK Analysis of BH009	Area Under the Curve From Time 0 Hours to Last Quantifiable Concentration (AUC0-last)	predose, 30 minutes, 45 minutes, 1 hour after the start of infusion (immediately after the end of infusion), 5 minutes, 15 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 24 hours, and 48 hours after the end of infusion
PK Analysis of BH009	Area Under the Curve From Time 0 Hours to Infinity (AUC0-inf)	predose, 30 minutes, 45 minutes, 1 hour after the start of infusion (immediately after the end of infusion), 5 minutes, 15 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 24 hours, and 48 hours after the end of infusion
PK Analysis of BH009	Apparent Terminal Elimination Half-Life (t1/2)	predose, 30 minutes, 45 minutes, 1 hour after the start of infusion (immediately after the end of infusion), 5 minutes, 15 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 24 hours, and 48 hours after the end of infusion
PK Analysis of BH009	Apparent Total Clearance (CL)	predose, 30 minutes, 45 minutes, 1 hour after the start of infusion (immediately after the end of infusion), 5 minutes, 15 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 24 hours, and 48 hours after the end of infusion
PK Analysis of BH009	Apparent Volume of Distribution (Vz/F)	predose, 30 minutes, 45 minutes, 1 hour after the start of infusion (immediately after the end of infusion), 5 minutes, 15 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 24 hours, and 48 hours after the end of infusion

Collaborators and Investigators

• Sponsor: Zhuhai Beihai Biotech Co., Ltd
• Investigators: Principal Investigator: Jing Wang, PI, Hunan Cancer Hospital; Principal Investigator: Yaqian Han, PI, Hunan Cancer Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 18, 2023
• Primary Completion (Estimated): March 30, 2024
• Study Completion (Estimated): April 30, 2024

Study Registration Dates

• First Submitted: January 19, 2024
• First Submitted That Met QC Criteria: January 29, 2024
• First Posted (Actual): January 31, 2024

Study Record Updates

• Last Update Posted (Estimated): February 2, 2024
• Last Update Submitted That Met QC Criteria: January 31, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Phase I
• Other Study ID Numbers: BH009-I-101; CTR20230004 (Other Identifier: NMPA)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No