Study of SKB264 in patients with advanced and hard-to-treat cancers who have not responded well to standard treatments.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Sichuan Kelun-Biotech Biopharmaceutical Co. Ltd.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

completed 10 Dec 2024

Decision date (initial)

2024-06-20

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd

External identifiers

EU CT number

2023-508700-38-00

ClinicalTrials.gov

NCT04152499

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Dose response, Others, Safety, Therapy, Efficacy, Pharmacokinetic

To evaluate the objective response rate (ORR) [Complete Response (CR) + Partial Response (PR)] of SKB264 when administered intravenously (IV) as monotherapy at the RDEs to patients with metastatic or locally advanced unresectable tumors.

Secondary objectives 5

1. To obtain additional characterization of the safety of SKB264 at the RDEs.
2. To evaluate efficacy in patients treated with SKB264 as monotherapy based on: - DOR - PFS - OS
3. To assess the immunogenicity of SKB264.
4. To characterize the PK of SKB264- ADC, SKB264-TAB, and free KL610023 payload.
5. To assess levels of TROP2 expression in tumor tissue and correlation of those levels with responses

Conditions and MedDRA coding

Metastatic or locally advanced unresectable solid tumors progressing after available standard therapies

Study design 3 periods

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

1. Patients must be able to provide documented voluntary informed consent.
2. ECOG Performance Status 0 or 1.
3. Male or female patient aged ≥ 18 years.
4. Histologically or cytologically documented, incurable, locally advanced, recurrent or metastatic cancer.
5. Measurable disease by CT/MRI.
6. Patients should have an unresectable locally advanced or metastatic solid tumor that is refractory to standard therapies.
7. Neutrophil count ≥ 1.5×109/L, platelet count ≥ 100×109/L, and hemoglobin ≥ 9 g/dL (without receiving blood transfusion, erythropoietin, recombinant human thrombopoietin or colony stimulating factor treatment within 2 weeks before screening).
8. International normalized ratio (INR) and activated partial thromboplastin time (aPTT) ≤ 1.5×ULN.
9. Serum total bilirubin ≤ 1.5 ×ULN (Patients with known Gilbert disease who have serum total bilirubin level ≤ 3 ×ULN may be enrolled), aspartate aminotransferase (AST), alanine aminotransferase (ALT)≤ 2.5 × upper limit of normal (ULN), with the exception of patients with hepatic metastases (ALT and AST ≤ 5 × ULN).
10. Creatinine clearance ≥ 30 mL/min calculated by Cockcroft-Gault, Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), or Modification of Diet in Renal Disease (MDRD) formulas. Note that 4-hour urine collection is not required but is allowed.
11. For female patients of childbearing potential and male patients with partners of childbearing potential, agreement (by patient and/or partner) to use a highly effective form(s) of contraception during study treatment.
12. Patients must have recovered (i.e., improvement to Grade 1 or better) from all acute toxicities from previous therapy, excluding alopecia and vitiligo. Note: Subjects with endocrine AE of any grade are permitted to enroll if they are stably maintained on appropriate replacement therapy and are asymptomatic.
13. Expected survival ≥ 3 months.

Exclusion criteria 24

1. Any patient who was treated in the Phase I part of this study.
2. Any standard cancer therapy (e.g. chemotherapy, hormonal therapy, immunotherapy, biologic therapy treatment, etc.) within 4 weeks, or any small molecular tyrosine kinase inhibitor (TKI), radiotherapy or therapy with traditional Chinese medicines approved for anti-tumor treatment within 2 weeks before first infusion of study drug.
3. Any major surgical procedure within 4 weeks of first infusion of study drug.
4. Diagnosed disease as below or active infection including: Hepatitis B/C or cirrhosis. With serious infections within 4 weeks prior to the first dose of study intervention (including but not limited to comorbidity, sepsis or severe pneumonia that require hospitalization) or concomitant infections requiring systemic antibiotic treatment within 2 weeks prior to the first dose of study intervention.
5. Have known prior positive test results or medical history for human immunodeficiency virus.
6. Uncontrolled hypertension (systolic blood pressure ≥ 160 mmHg and/or diastolic blood pressure ≥100 mmHg) or diabetes.
7. Subjects who require use of strong inhibitors or inducers of CYP3A4 at least 14 days prior to and throughout Study. Use of strong inhibitors or inducers of CYP3A4 is not allowed in this Study.
8. Pregnancy or lactation.
9. Any experimental therapy within 4 weeks or 5 half-lives, whichever is shorter, of first infusion of study drug.
10. Severe or uncontrolled cardiac disease requiring treatment, congestive heart failure (New York Heart Association) III or IV, unstable angina pectoris that couldn’t be controlled by medication, history of myocardial infarction during the last 6 months, serious arrhythmias requiring medication (with exception of atrial fibrillation or paroxysmal supraventricular tachycardia).
11. Subjects with known meningeal metastases, brainstem metastases, spinal cord metastases and/or compression, or other active CNS metastases. For further details refer to protocol.
12. Patients with active second primary cancers (except for cured in situ nonmelanoma skin cancer and in situ cervical cancer with no relapse in the last 3 years, or other malignant cancers that have been cured and no evidence of recurrence).
13. Require supplemental oxygen for daily activities.
14. Documented Grade ≥ 2 peripheral neuropathy.
15. History of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, corneal disease that prevents/delays corneal healing, macular degeneration.
16. Patients previously treated with TROP2 targeted therapies at any time for early stage or metastatic disease.
17. Left ventricular ejection fraction < 45% determined by echocardiogram or multiple-gated acquisition scan.
18. Resting QTcF > 480 msec at baseline.
19. Ascites requiring paracentesis >1 per week.
20. Symptomatic pleural effusion (< 90% oxygen saturation).
21. History of interstitial lung diseases (ILD) or non-infectious pneumonitis requiring steroid treatments, or current ILD/pneumonitis, or where ILD/pneumonitis cannot be ruled out by imaging at screening; severe pulmonary dysfunction caused by lung diseases.
22. New diagnosed thromboembolic events that requires therapeutic intervention over the last 6 months (patients with stable control of lower limb deep venous thrombosis are allowed).
23. Known allergic to any components of SKB264, including excipients (including polysorbate-20); or history of severe hypersensitivity to another biologic therapy.
24. The investigator considers other situations that patients are not appropriate to participate in this trial.For participants in the EU, this includes those who, in the opinion of the investigator, could benefit from existing alternative treatment options within the current ESMO ( European Society For Medical Oncology) guidelines for each indication and setting. For further details please refer to protocol.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. ORR (the percentage of patients who achieve CR/PR) per RECIST 1.1

Secondary endpoints 1

1. Percentage of patients with adverse events, serious adverse events DOR.PFS (time frame: baseline to the end of the study).OS (time frame: baseline to the end of the study).Immunogenicity of SKB264.PK parameters for SKB264-ADC, SKB264-TAB, and free KL610023 payload.Levels of TROP2 expression in tumor tissue and correlation of those levels with responses.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Auxiliary 10

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Sichuan Kelun-Biotech Biopharmaceutical Co. Ltd.

Sponsor organisation

Sichuan Kelun-Biotech Biopharmaceutical Co. Ltd.

Address

No 666 Xinhua Avenue, Chengdu Cross-strait Science And Technology Industry Development Park, Wenjiang District Chengdu Cross-strait Science And Technology Industry Development Park Wenjiang District

City

Chengdu

Postcode

611138

Country

China

Scientific contact point

Organisation

Sichuan Kelun-Biotech Biopharmaceutical Co. Ltd.

Contact name

Xiaoping Jin (PhD, Chief Medical Officer)

Public contact point

Organisation

Sichuan Kelun-Biotech Biopharmaceutical Co. Ltd.

Contact name

Yaling Li

Third parties 10

Locations

2 EU/EEA countries · 9 investigational sites

By country

Investigational sites

Application history

1 submissions — initial application plus substantial / non-substantial modifications