A Study of SI-B003, a PD-1/CTLA-4 Bispecific Antibody, in Patients With Advanced Solid Tumors

NCT04606472 | Active Not Recruiting Phase 1 DMC

• 1 other identifier: SI-B003-101
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 8

Brief Summary

In phase Ia study, the safety and tolerability of SI-B003 in patients with recurrent or metastatic solid tumors will be investigated to determine the dose-limiting toxicity (DLT), maximum tolerated dose (MTD) or maximum administered dose (MAD) for MTD is not reached of SI-B003. In the phase Ib study, the safety and tolerability of SI-B003 in specific tumors will be further investigated by selecting multiple doses based on the results of phase Ia study or/and the fixed-dose administration method with the closest exposure level, and recommended phase II dose (RP2D) for phase II clinical studies will be determined.

Conditions

Solid Tumor

Keywords

Non-small cell lung cancer (NSCLC); Renal cell carcinoma (RCC); Urothelial Cancer (UC); Metastatic colorectal cancer (mCRC); Triple negative breast cancer (TNBC); Melanoma

Outcome Measures

Primary Outcomes (5)

• Phase Ia: Dose limiting toxicity (DLT)

  DLTs is assessed according to NCI-CTCAE v5.0 during the first cycle (28 days) and were defined as occurrence of any of the following toxicities if judged by the investigator to be possibly, probably or definitely related to study drug administration.

  Up to 28 days after the first dose of SI-B003

• Phase Ia: Maximum tolerated dose (MTD)

  MTD is defined as the dose with the estimated DLT rate closest to the target DLT rate (33%) is selected as the MTD. If there are two or more estimated values close to the target DLT rate and the same, when the estimated value is lower than the target DLT rate, choose the higher dose, and when the estimated value is greater than or equal to the target toxicity rate, choose a lower dose.

  Up to 28 days after the first dose of SI-B003

• Phase Ia: Maximum administered dose (MAD)

  MAD is defined as the maximum administered dose, when MTD is not reached.

  Up to 28 days after the first dose of SI-B003

• Phase Ia: 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 SI-B003. The type, frequency and severity of TEAE will be evaluated during the treatment of SI-B003.

  Up to approximately 24 months

• 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 the dose expansion arms, based on safety, tolerability, efficacy, PK, and PD data collected during the dose escalation study of SI-B003.

  Up to 28 days after the first dose of SI-B003

Secondary Outcomes (18)

• Cmax

  Up to 28 days after the first dose of SI-B003

• Tmax

  Up to 28 days after the first dose of SI-B003

• T1/2

  Up to 28 days after the first dose of SI-B003

• AUC0-t

  Up to 28 days after the first dose of SI-B003

• CL

  Up to 28 days after the first dose of SI-B003

Study Arms (1)

Study treatment

EXPERIMENTAL

Participants receive SI-B003 as intravenous infusion for the first cycle (4 weeks). Participants with clinical benefit could receive additional treatment for more cycles. The administration will be terminated because of disease progression or intolerable toxicity occurring or other reasons.

Drug: SI-B003

Interventions

SI-B003 DRUG

Administration by intravenous infusion.

Study treatment

Eligibility Criteria

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

You may qualify if:

• The participants could understand and sign the informed consent form, and must participate voluntarily.
• No gender limit.
• Age: ≥18 years old and ≤75 years old (phase Ia); ≥18 years old (phase Ib).
• Expected survival time ≥ 3 months.
• Histologically or cytologically confirmed recurrent or metastatic solid tumor, clinical stage IIIB/IV, with radiographic or other objective evidence of disease progression after standard therapy; Or subjects were patients with solid tumors that were refractory to treatment, patients with solid tumors that did not have standard treatment, or patients who could not tolerate or had contraindications to standard treatment.
• For the phase Ib study:
• Cohort\_A: Histologically or cytologically confirmed advanced gastric adenocarcinoma (GC) or gastroesophageal junction (GEJ) adenocarcinoma after exposure to platinum-based chemotherapy after receiving only first-line anti-PD-1 (L1) monoclonal antibody during systemic therapy; Cohort\_B: Histologically or cytologically confirmed patients with malignant mesothelioma not suitable for surgery;
• Consent to provide archival tumor tissue or fresh tissue samples of the primary or metastatic tumor, if not available, at the discretion of the investigator (only for stage Ib );
• At least one measurable lesion that meets the definition of RECIST v1.1 at baseline (only for stage Ib).
• Patients treated with anti-PD-1 (L1) -containing monoclonal antibody must have progression of resistance after benefit from anti-PD-1 (L1) -containing monoclonal antibody (phase Ib only);
• Physical fitness score ECOG 0 or 1 point.
• The adverse reactions of previous antineoplastic therapy returned to CTCAE 5.0 grade ≤1 (except for toxicities without safety risks judged by investigators, such as alopecia, grade 2 peripheral neurotoxicity, and hypothyroidism stable with hormone replacement therapy);
• No severe cardiac dysfunction, left ventricular ejection fraction ≥50%;
• The organ function within 7 days prior to the first administration meets the following requirements:
• Bone marrow: absolute neutrophil count (ANC) ≥1.5×109/L, hemoglobin ≥90 g/L, platelet count ≥100×109/L (participants with liver cancer ANC ≥75×109/L);

You may not qualify if:

• Parenchymal or leptomeningeal metastases with clinical symptoms who were judged by the investigator to be ineligible for enrollment;
• Participants who participated in any other clinical trial within 28 days before the administration of this trial, except for clinical trials of marketed drugs;
• Chemotherapy, biological therapy, immunotherapy, radical radiotherapy, major surgery, targeted therapy (including small molecule inhibitor of tyrosine kinase), and other anti-tumor therapy within 4 weeks or 5 half-lives (whichever is shorter) prior to the first administration; mitomycin and nitrosoureas treatment within 6 weeks prior to the first administration; oral fluorouracil-like drugs such as S-1, capecitabine, or palliative radiotherapy within 2weeks prior to the first administration.
• Major surgery (investigator-defined) within 4 weeks before the first dose.
• In 14 days prior to administration of this study, those who have received systemic corticosteroids (\>10mg/day prednisone, or equivalent other corticosteroids) or immunosuppressive therapy should be excluded except for those who have received inhaled or topical corticosteroids, or hormone therapy of physiological replacement dose due to adrenal insufficiency.
• Pulmonary disease grade ≥3 according to NCI-CTCAE v5.0; Patients with existing interstitial lung disease (ILD).
• Severe systemic infection occurred within 4 weeks before screening, including but not limited to severe pneumonia caused by fungi, bacteria, viruses, bacteremia, or serious infectious complications.
• Participants at risk of active autoimmune diseases, or with a history of autoimmune diseases, including but not limited to Crohn's disease, ulcerative colitis, systemic lupus erythematosus, sarcoidosis, Wegener syndrome (polyangiitis granuloma Disease, Graves' disease, rheumatoid arthritis, pituitary inflammation, uveitis), autoimmune hepatitis, systemic sclerosis, Hashimoto's thyroiditis, autoimmune vasculitis, autoimmune neuropathy (Guillain-Barré syndrome), etc. Except for the following conditions: Type I diabetes, hormone replacement therapy for stable hypothyroidism (including hypothyroidism caused by autoimmune thyroid disease), psoriasis or vitiligo that does not require systemic treatment.
• Complicated with other malignant tumors within 2 years prior to the first administration, except for cured skin squamous cell carcinoma, basal cell carcinoma, superficial bladder cancer, prostate/cervix/breast carcinoma in situ (only phase Ib).
• Participants with human immunodeficiency virus antibody (HIVAb) positive, active tuberculosis, active hepatitis B virus infection (HBV-DNA copy number\> 104) or hepatitis C virus (HCV) infection.
• Participants with poorly controlled hypertension by two kinds of antihypertensive drugs (systolic blood pressure\>150 mmHg or diastolic blood pressure\>100 mmHg).
• A history of severe cardiovascular and cerebrovascular diseases, including but not limited to:
• Severe cardiac rhythm or conduction abnormalities, such as ventricular arrhythmia requiring clinical intervention, Ⅲ degree atrioventricular block, etc.
• At rest, the QT interval was prolonged (QTc \> 450 msec in men or QTc \> 470 msec in women); Acute coronary syndrome, congestive heart failure, aortic dissection, stroke, or other grade 3 or higher cardiovascular and cerebrovascular events occurred within 6 months before the first dose; Patients with New York Heart Association (NYHA) functional class ≥II heart failure.
• Previous history of allogeneic bone marrow or organ transplantation.

Sponsors & Collaborators

• Sichuan Baili Pharmaceutical Co., Ltd.: lead
• SystImmune Inc.: collaborator

Study Sites (8)

Beijing Cancer Hospital

Beijing, Beijing Municipality, 100142, China

Location

Chongqing University Cancer Hospital

Chongqing, Chongqing Municipality, China

Location

The First Affiliated Hospital of Xiamen University

Xiamen, Fujian, China

Location

Henan Cancer Hospital

Zhengzhou, Henan, 450008, China

Location

Hubei Cancer Hospital

Wuhan, Hubei, China

Location

Union Hospital Tongji Medical College, Huazhong University of Science and Technology

Wuhan, Hubei, China

Location

Shanghai Central Hospital

Shanghai, Shanghai Municipality, China

Location

West China Hospital, Sichuan University

Chengdu, Sichuan, China

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Carcinoma, Renal Cell; Colorectal Neoplasms; Triple Negative Breast Neoplasms; Melanoma

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Breast Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms

Study Officials

• Lin Shen

  Peking University Cancer Hospital & Institute

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: October 8, 2020
• First Posted: October 28, 2020
• Study Start: November 10, 2020
• Primary Completion: December 1, 2025
• Study Completion: December 1, 2025
• Last Updated: September 26, 2025

Record last verified: 2025-09

Locations

CN (8)