JSKN033 treatment for advanced solid tumors

Phase I/II Study to Assess the Safety, Tolerability, Pharmacokinetics and Efficacy of JSKN033 in Patients With Advanced or Metastatic Solid Malignant Tumors

This study is testing a new treatment called JSKN033 to see if it can help people with advanced solid tumors that have a certain protein called HER2.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Jiangsu Alphamab Biopharmaceuticals Co., Ltd (Industry-sponsored)
• Drugs / interventions: prednisone, envafolimab
• Locations: 1 site (Randwick, New South Wales)
• Trial ID: NCT06226766 on ClinicalTrials.gov

What this trial studies

This is an open-label, multicenter, first-in-human Phase I/II study evaluating the safety, tolerability, pharmacokinetics, immunogenicity, and efficacy of JSKN033 in patients with advanced unresectable or metastatic solid malignant tumors expressing HER2. The study consists of a dose escalation phase where participants receive varying doses of JSKN033, followed by a dose expansion phase focusing on gastrointestinal tumors with HER2 expression. Participants will be monitored for adverse events and treatment efficacy throughout the study.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with advanced unresectable or metastatic solid tumors expressing HER2 that have not responded to standard treatments.

Not a fit: Patients with solid tumors that do not express HER2 or those who have not exhausted standard treatment options may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with advanced solid tumors that are difficult to treat.

How similar studies have performed: Other studies targeting HER2 expression in solid tumors have shown promising results, indicating potential for success with this approach.

Eligibility criteria

Inclusion Criteria:

1. Be willing and able to provide written informed consent form (ICF) for the trial.
2. Male or female, 18 years of age or older; willing and able to complete all required procedures of study.
3. Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1, and life expectancy ≥ 12 weeks.
4. Must have a pathologically documented advanced unresectable or metastatic solid malignant tumor (gastrointestinal tumor for dose expansion phase) with HER2 expression (IHC ≥1+) that is refractory to or intolerable with standard treatment, or for which no effective standard treatment is available. HER2 mutation in patients with NSCLC is also regarded as HER2 expression.
5. Baseline measurable disease according to RECIST 1.1. Target lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
6. Adequate organ function assessed within 7 days prior to first trial treatment \[had not received blood transfusion, erythropoietin (EPO), granulocyte colony stimulating factor (G-CSF) or other relevant medical support within 14 days before the administration of the investigational product\].
7. Have adequate treatment washout period before first dose.
8. Have LVEF ≥50% by either echo cardiography (ECHO) or multiple-gated acquisition (MUGA) within 28 days prior to first dose.
9. Female or male patients of childbearing potential should be willing to use a highly effective method of contraception (with a failure rate of less than 1.0% per year) from first study treatment to 180 days after completion of study treatment. Female of childbearing potential should have a negative pregnancy test within 7 days prior to first trial treatment (childbearing potential is defined as premenopausal females without documented tubal ligation or hysterectomy, or postmenopausal females within 1 year).

Exclusion Criteria:

1. Patients with untreated active brain metastases or meningeal or spinal cord metastases are excluded. If the subject has received treatment for brain metastases and the metastases are stable (as evidenced by brain imaging within 28 days prior to study treatment showing stable disease, no new lesions, and no new neurological symptoms, and no requirement for steroids for at least 14 days prior to study treatment), they may be eligible for enrollment.
2. Concurrent malignancy within 5 years prior to first dose other than adequately treated cervical carcinoma-in-situ, localized squamous cell cancer of the skin, basal cell carcinoma, prostate cancer, thyroid cancer not requiring treatment, ductal carcinoma in situ of the breast, or \< T1 urothelial carcinoma.
3. Prior treatment with an antibody-drug conjugate (ADC) which consists of a topoisomerase I inhibitor derivative.
4. History of uncontrolled concurrent illness.
5. Has a history of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required steroids or current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by image at screening.
6. Previous severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infection either suspected or confirmed within 4 weeks prior to screening. Acute symptoms will be excluded, or must have resolved and based on investigator assessment, there are no sequela that would place participant at a higher risk of receiving investigational treatment.
7. Patients with ascites, pleural effusion, pericardial effusion which cannot be controlled by appropriate interventions.
8. Have unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia, grade 2 hypoparathyroidism) related to prior anticancer therapy and stable anemia not yet resolved to grade ≤ 1 (NCI-CTCAEV5.0).
9. Patients with a condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids, and adrenal replacement doses ≤ 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. A brief course of corticosteroids for the prophylaxis (e.g., contrast dye allergy) or treatment of non-autoimmune conditions (e.g., delayed-type hypersensitivity reaction caused by contact allergen) is permitted.
10. History of life-threatening hypersensitivity or known to be allergic to protein drugs or recombinant proteins or excipients in JSKN033 drug formulation.
11. Prior history of anti-HER2 therapy induced angioedema, or severe hypotension and Severe allergic reactions to other antibody drugs or topoisomerase I inhibitors.
12. Other conditions that, in the investigators' opinion, would make patients inappropriate to participate in this study, such as a history of mental illness, alcoholism or drug abuse.

Where this trial is running

Randwick, New South Wales

• Scientia Clinical Research — Randwick, New South Wales, Australia (Recruiting)

Study contacts

• Principal investigator: Charlotte Lemech — Scientia Clinical Research
• Study coordinator: Grace Yueun Hwang

Conditions Advanced Solid Tumor