To Evaluate the Phase I Clinical Study of JSKN016 in Chinese Patients With Advanced Malignant Solid Tumors

NCT06592417 | Recruiting Phase 1

• 1 other identifier: JSKN016-101
• Study Type: interventional
• Target: 140
• Locations: 1 country
• Sites: 2

Brief Summary

This is a Phase I open, multi-center, first-in-human study evaluating JSKN016 in subjects with advanced metastatic solid tumors, divided into dose escalation and dose extension.

Conditions

Advanced Malignant Solid Tumor

Outcome Measures

Primary Outcomes (4)

• Incidence of DLTs

  DLTs are defined as one or more serious toxic reactions that occur within 21 days (Q3W) after the start of dosing and are determined to be reasonably associated with the study drug

  21 days after the first dose for subjects at dose escalation stage

• The frequency and severity of treatment-related adverse events (TEAE), treatment-related adverse events (TRAE), and serious adverse events (SAE).

  Clinically significant changes in lab test findings

  From first dose to 30 days after last dose

• MTD or RP2D of JSKN 016

  To determinate MTD and/ or RP2D of JSKN016

  Postdose of last participant up to 1 year

• Objective Response Rate (ORR) in Extended queue

  Objective response rate (ORR) was defined as the proportion of participants who achieve either complete response \[CR\] or partial response \[PR\] per Response Evaluation Criteria in Solid Tumors (RECIST v1.1）

  Postdose of last participant up to 1 year

Secondary Outcomes (6)

• Clinical benefit rates (CBR)

  Postdose of last participant up to 1 year

• Cmax of JSKN016

  Predose to 90 days after last dose

• Tmax of JSKN016

  Predose to 90 days after last dose

• AUC of JSKN016

  Postdose of last participant up to 1 year

• Terminal Elimination Half-life (t1/2)

  Postdose of last participant up to 1 year

Study Arms (1)

Dose escalation/expansion

EXPERIMENTAL

The subjects at dose escalation stage will be administered with investigational product (JSKN016) starting at 0.5 mg/kg, followed by1 mg/kg，2 mg/kg，4 mg/kg，6 mg/kg，7 mg/kg，8 mg/kgmg/kg, IV ,Q3W The subjects at dose expansion stage will be adiministered with JSKN016 at 6mg/kg or more(anticipated response dose)

Drug: JSKN016 injection

Interventions

JSKN016 injection DRUG

JSKN016 is a bispecific antibody drug conjugate targeting HER3 and TROP2.

Dose escalation/expansion

Eligibility Criteria

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

You may qualify if:

• \. Subjects can understand the informed consent form, voluntarily participate in and sign the informed consent form; 2. The subjects were ≥18 years old on the day of signing the informed consent, male or female; 3. Subjects with histologically and/or cytologically confirmed advanced unresectable or metastatic epithelial malignancies that have failed or are intolerable to previous standard therapies, preferentially but not limited to the following types: AGA-positive non-small cell lung cancer, HER2 IHC 0 breast cancer, etc.
• \. For AGA-positive NSCLC, the presence of at least one of the following mutations is required; EGFR, ALK, ROS1, NTRK, BRAF V600, MET exon 14, RET, KRAS G12C, or HER2;
• For the enrolled subjects, the above driver gene mutations were not tested, but the previous test results confirmed by the investigators were accepted;
• If only EGFR overexpression without driver gene mutation can not be included;
• Prior osimertinib therapy is required if EGFR T790M mutation is present;
• Participants had to have failed at least one prior targeted therapy and at least platinum-based chemotherapy with or without an immune checkpoint inhibitor or antiangiogenic agent; 5. Breast cancer patients with HER2 IHC 0 expression, regardless of hormone receptor (HR) expression, could be enrolled according to the results of IHC examination in our center.
• \. At least one measurable lesion at baseline according to RECIST 1.1 criteria. Measurable disease required either no previous local treatment (e.g., radiotherapy) or evidence of disease progression after local treatment.
• \. Expected survival time ≥3 months; 8. ECOG score 0 or 1; 9. Female subjects of childbearing potential or male subjects with a fertile partner agreed to use highly effective contraception from the time they provided written informed consent until 24 weeks after the last dose. Female subjects of childbearing potential had to have a negative serum/urine pregnancy test within 7 days before randomization (for women of childbearing age, see Appendix 2).
• \. Adequate organ function within 7 days before randomization:
• Bone marrow function: absolute neutrophil count ≥1.5×109/L; Hemoglobin ≥90 g/L; Platelet count ≥100×109/L (no whole blood or blood component transfusion within 14 days before randomization; No administration of hematopoietic cytokines within 7 days before randomization).
• Liver function (based on the normal value of each clinical research center) : total bilirubin \< 1.5 times the upper limit of normal value (ULN, total bilirubin in subjects with liver metastasis ≤3 x ULN); ALT/AST≤3×ULN (≤5×ULN in patients with liver metastasis); Albumin ≥28g/L; Renal function: serum creatinine ≤1.5 times the upper limit of normal, or creatinine clearance (Ccr) calculated according to Cockcroft-Gault formula (see Appendix 4) ≥ 60 mL/min; Coagulation function: INR or PT≤ 1.5x ULN, and aPTT≤ 1.5x ULN (low stable dose of anticoagulant, such as aspirin 100 mg/ day is allowed); 11. Left ventricular ejection fraction (LVEF) ≥50% (by echocardiography \[ECHO\]); 12. Participants were able and willing to comply with protocol-specified visits, treatment plans, laboratory tests, and other study-related procedures.

You may not qualify if:

• \. Patients with symptoms of active central nervous system metastases, except those with stable parenchymal brain metastases as assessed by investigators, were defined as seizure-free for more than 12 weeks with or without the use of antiepileptic drugs; No need for glucocorticoids; At least one MRI showed that the patient was stable on imaging. Or stable after treatment for more than 1 month without symptoms; 2. Received any investigational drug within 28 days before dosing; 3. Receipt of other antineoplastic therapy within 28 days before dose or within 5 half-lives of previous antineoplastic drugs, whichever is shorter but requires a minimum of 14 days; Received Chinese herbal medicine with clear anti-tumor indications within 14 days before drug administration; 4. Local palliative treatment within 14 days before administration; 5. Major surgical treatment (such as transabdominal or transthoracic surgery) within 28 days before drug administration; Excluding minor procedures such as diagnostic punctures or infusion device implantation or biliary stenting) or anticipated need for major surgical treatment during the study period; 6. Gastrointestinal abnormalities with obvious clinical manifestations, including but not limited to: intestinal obstruction or the presence of symptoms and signs of intestinal obstruction within 6 months before drug administration, but if the obstruction was completely removed after surgical treatment, screening could be performed (patients with previous intestinal stent implantation and the intestinal stent was not removed during the screening period were not allowed); Patients with gastrointestinal perforation, gastrointestinal fistula, intra-abdominal abscess and non-gastrointestinal fistula (such as tracheoesophageal fistula) within 6 months before administration; Patients with gastrointestinal bleeding (CTCAE≥ grade 3) within 6 months before treatment, or gastrointestinal bleeding (melena, bloody stool, etc.) within 1 month before randomization were eligible if hemorrhoid bleeding was confirmed or only showed positive fecal occult blood.
• \. Subjects with uncontrolled massive serous effusion or moderate to massive serous effusion requiring repeated drainage (recurrence within 2 weeks after intervention) such as pleural effusion, pericardial effusion, ascites, cachexia, etc.
• \. Always received including the antibody coupling of topoisomerase inhibitors class I drug therapy, such as DS-8201, HER3-DXd, DS-1062, etc; 9. A history of (noninfectious) interstitial lung disease (ILD) or noninfectious pneumonia requiring steroid therapy, current ILD or noninfectious pneumonia, or ILD or noninfectious pneumonia that could not be ruled out by imaging at screening; 10. Other malignant tumors within 5 years before drug administration, Cured cutaneous squamous cell carcinoma, basal cell carcinoma, non-primary invasive bladder cancer (defined as stage ≤T2a, Gleason score ≤6, and at the time of prostate cancer diagnosis) were excluded Patients with PSA≤10ng/mL (if measured) who had received radical treatment and had no PSA biochemical recurrence could participate in the study), in situ prostate/cervix/breast cancer; 11. Have uncontrolled comorbidities, including but not limited to the following:
• Active HBV or HCV infection Patients with HBsAg (+) and HBV-DNA\< 2500 copies /mL or 500 IU/mL were allowed to be enrolled. HCV-Ab (+) and HCV-RNA negative were allowed to enroll.
• HIV infection;
• Known active tuberculosis; Active syphilis;
• Active or uncontrolled infection requiring systemic anti-infective treatment; Uncontrolled hypertension (systolic blood pressure ≥160mmHg, Diastolic blood pressure \> 100 mmHg), symptomatic heart failure (NYHA II-IV), unstable angina or myocardial infarction within 6 months, history of heart failure or systolic dysfunction (LVEF\<50%), or risk of QTc prolongation or arrhythmia (baseline QTc\>470 msec) ), intractable hypokalemia, long QT syndrome, tachycardia at rest with a heart rate \>100 bpm, atrial fibrillation or clinically symptomatic valvular heart disease (if well controlled by treatment), moderate-severe pulmonary hypertension, or a history of other arrhythmias of medical importance).
• Newly diagnosed thromboembolic events requiring treatment within 6 months (patients with well-controlled deep-vein thrombosis of the lower extremities or venous access ports were allowed).
• \. The toxicity of previous antineoplastic therapy did not recover to CTCAE grade ≤1 (NCI-CTCAE v5.0); Note: Subjects with stable CTCAE grade 2 toxicity related to previous antineoplastic therapy (defined as stable toxicity severity and no CTCAE grade greater than 2 within 3 months before dose administration) could be enrolled, such as: Chemotherapy-induced neurotoxicity, alopecia, skin pigmentation, fatigue, endocrine toxicity caused by previous immunotherapy (such as thyroid dysfunction, diabetes, hyperglycemia, adrenal insufficiency); 13. Previous history of allogeneic bone marrow or organ transplantation; 14. Previous history of allergic reaction or anaphylaxis to antibody drugs; 15. Previous history of severe dry eye, severe meibomian gland disease and/or blepharitis, keratopathy and maculopathy resulting in untreatable or delayed corneal healing of the subject; 16. Pregnant and/or lactating women; 17. Other conditions considered by the investigators to affect the safety or compliance of the study drug treatment, including but not limited to mental disorders, alcohol or drug abuse, etc.

Sponsors & Collaborators

• Jiangsu Alphamab Biopharmaceuticals Co., Ltd: lead

Study Sites (2)

Fujian Cancer Hospital

Fuzhou, Fujian, 350014, China

RECRUITING

Sun Yat-sen Hospital, Sun Yat-sen University

Guangzhou, Guangdong, 510080, China

RECRUITING

Study Officials

• Jieqiong Liu

  Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

herui yao yaoherui, D.PH

CONTACT

13500018020; yaoherui@163.com

Study Design

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

Model Details: Sequential Assignment

Study Record Dates

• First Submitted: April 28, 2024
• First Posted: September 19, 2024
• Study Start: April 30, 2024
• Primary Completion (Estimated): May 17, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: September 19, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)