A Study of BL-B16D1 in Patients With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma and Other Solid Tumors

Solid Tumor Clinical Trial

Official title:

A Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of BL-B16D1 in Patients With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma and Other Solid Tumors

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06469008
• Other study ID #: BL-B16D1-102
• Status: Not yet recruiting
• Phase: Phase 1
• Start date: July 2024
• Est. completion date: July 2026

Study information

• Verified date: June 2024
• Source: Sichuan Baili Pharmaceutical Co., Ltd.
• Contact: Sa Xiao, PHD
• Phone: 15013238943
• Email: xiaosa[@]baili-pharm.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is an open, multicenter, increasing dose and dose extension nonrandomized phase I clinical study to evaluate the safety, tolerance, pharmacokinetic characteristics and preliminary effectiveness of BL-B16D1 in recurrent or metastatic head and neck squamous cell carcinomas and other solid tumors.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 21
• Est. completion date: July 2026
• Est. primary completion date: July 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Sign the informed consent form voluntarily and follow the protocol requirements;

2. Gender is not limited;

3. Age: =18 years old and =75 years old (phase Ia); =18 years old (phase Ib);

4. Expected survival time =3 months;

5. Patients with pathologically and/or cytologically confirmed recurrent or metastatic head and neck squamous cell carcinoma and other solid tumors who failed or could not receive standard treatment;

6. Agreed to provide primary tumors or metastases 3 years archive of tumor tissue samples or fresh tissue samples;

7. Must have at least one accord with RECIST v1.1 define measurable lesions;

8. ECOG physical status 0 or 1;

9. The toxicity of previous antineoplastic therapy has returned to = grade 1 as defined by NCI-CTCAE v5.0;

10. No severe cardiac dysfunction, left ventricular ejection fraction =50%;

11. The organ function level must meet the requirements if the patient has not received blood transfusion or hematopoietic stimulating factor therapy within 14 days before screening;

12. Blood coagulation function: international standardization ratio (INR) 1.5 or less, and the part activated clotting time (APTT) live enzymes ULN 1.5 or less;

13. Urinary protein =2+ or =1000mg/24h;

14. For premenopausal women with childbearing potential, a pregnancy test must be performed within 7 days before starting treatment, serum pregnancy must be negative, and the patient must not be lactating; All the patients (no matter male or female) shall be 6 months after the end of the treatment period and adequate precautions.

Exclusion Criteria:

1. Antineoplastic therapy within 4 weeks or 5 half-lives before the first dose; Mitomycin and nitrosoureas were administered within 6 weeks before the first dose; Oral drugs such as fluorouracil;

2. Had received previous ADC drug therapy with MMAE/MMAF as toxin;

3. History of severe heart disease;

4. QT prolongation, complete left bundle branch block, III degree atrioventricular block;

5. Active autoimmune and inflammatory diseases;

6. Before the first delivery within 5 years diagnosed as other malignant tumor;

7. Hypertension poorly controlled by two antihypertensive drugs (systolic blood pressure > 150 mmHg or diastolic blood pressure > 100 mmHg);

8. Patients with poor glycemic control;

9. Present with grade =1 radiation pneumonitis according to the RTOG/EORTC definition; Previous history of ILD or current ILD, or suspicion of such disease during screening;

10. Complicated with pulmonary diseases leading to clinically severe respiratory function impairment;

11. There is activity of the central nervous system symptoms;

12. Patients with a history of allergy to recombinant humanized or human-mouse chimeric antibodies or to any of the excipients of BL-B16D1;

13. Before transplant or allogeneic hematopoietic stem cell transplantation (Allo - HSCT);

14. Previous anthracycline-based adjuvant therapy (new), the cumulative dose anthracycline-based drugs > 360 mg/m2;

15. Human immunodeficiency virus antibody positive, active tuberculosis, active hepatitis B virus infection or active hepatitis C virus infection;

16. Severe infection occurred within 4 weeks before the first dose; Signs of pulmonary infection or active pulmonary inflammation within 2 weeks before the first dose;

17. Patients with massive or symptomatic effusions or poorly controlled effusions;

18. Had participated in another clinical trial within 4 weeks before the first dose (calculated from the time of the last dose);

19. Had the following ocular diseases: a. active infection or corneal ulcer; b. monocular vision; c. a history of corneal transplantation; d. Contact lens dependence; e. Uncontrolled glaucoma; f. Uncontrolled or progressive retinopathy, wet macular degeneration, etc.;

20. Other circumstances that the investigator deemed inappropriate for participation in the trial.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Solid Tumor
• Squamous Cell Carcinoma of Head and Neck

Intervention

Drug:
• BL-B16D1
Administration by intravenous infusion for a cycle of 3 weeks.

Locations

Country	Name	City	State
China	Shanghai East Hospital	Shanghai	Shanghai

Sponsors (2)

Lead Sponsor	Collaborator
Sichuan Baili Pharmaceutical Co., Ltd.	Baili-Bio (Chengdu) Pharmaceutical Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase Ia: Dose limiting toxicity (DLT)	DLTs are assessed according to NCI-CTCAE v5.0 during the first cycle and defined as occurrence of any of the toxicities in DLT definition if judged by the investigator to be possibly, probably or definitely related to study drug administration.	Up to 21 days after the first dose
Primary	Phase Ia: Maximum tolerated dose (MTD)	MTD is defined as the highest dose level at which no more than 1 in 6 participants experienced a DLT during the first cycle .	Up to 21 days after the first dose
Primary	Phase Ib: Recommended Phase II Dose (RP2D)	The RP2D is defined as the dose level chosen by the sponsor (in consultation with the investigators) for phase II study, based on safety, tolerability, efficacy, PK, and PD data collected during the dose escalation study of BL-B16D1.	Up to approximately 24 months
Secondary	Treatment-Emergent Adverse Event (TEAE)	TEAE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally emerging, or any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition during the treatment of BL-B16D1 . The type, frequency and severity of TEAE will be evaluated during the treatment of BL-B16D1.	Up to approximately 24 months
Secondary	Cmax	Maximum serum concentration (Cmax) of BL-B16D1 will be investigated.	Up to approximately 24 months
Secondary	Tmax	Time to maximum serum concentration (Tmax) of BL-B16D1 will be investigated.	Up to approximately 24 months
Secondary	T1/2	Half-life (T1/2) of BL-B16D1 will be investigated.	Up to approximately 24 months
Secondary	AUC0-t	AUC0-t is defined as area under the serum concentration-time curve from time 0 to the time of the last measurable concentration.	Up to approximately 24 months
Secondary	CL (Clearance)	CL in the serum of BL-B16D1 per unit of time will be investigated.	Up to approximately 24 months
Secondary	Ctrough	Ctrough is defined as the lowest serum concentration of BL-B16D1 prior to the next dose will be administered.	Up to approximately 24 months
Secondary	ADA (anti-drug antibody)	Frequency of anti-BL-B16D1 antibody (ADA) will be investigated.	Up to approximately 24 months
Secondary	Phase Ib: Objective Response Rate (ORR)	ORR is defined as the percentage of participants, who has a CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions). The percentage of participants who experiences a confirmed CR or PR is according to RECIST 1.1.	Up to approximately 24 months
Secondary	Phase Ib: Disease Control Rate (DCR)	The DCR is defined as the percentage of participants who has a CR, PR, or Stable Disease (SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease [PD: at least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD]).	Up to approximately 24 months
Secondary	Phase Ib: Duration of Response (DOR)	The DOR for a responder is defined as the time from the participant's initial objective response to the first date of either disease progression or death, whichever occurs first.	Up to approximately 24 months