臨床研究等提出・公開システム

A Single-arm, Open-label, Phase II Study to Evaluate Clinical Efficacy, Safety and Pharmacokinetics of HLX10 (Recombinant Humanized Anti-PD-1 Monoclonal Antibody Injection) in Combination with Chemotherapy (Carboplatin-Etoposide) in Previously Untreated Japanese Patients with Extensive Stage Small Cell Lung Cancer (ES-SCLC)

A Single-arm, Open-label, Phase II Study to Evaluate Efficacy,, Safety and Pharmacokinetics of HLX10 + Chemotherapy (Carboplatin- Etoposide) in Patients with Extensive Stage Small Cell Lung Cancer (ES-SCLC)

Hatakeyama Yu

CMIC Co., Ltd.

1-1-1, Shibaura, Minato-ku, Tokyo

ClinicalTrialInformation@cmic.co.jp

Hatakeyama Yu

CMIC Co., Ltd.

1-1-1, Shibaura, Minato-ku, Tokyo

+81-3-6779-8000

ClinicalTrialInformation@cmic.co.jp

Not Recruiting

April. 04, 2025

Interventional

single arm study

open(masking not used)

uncontrolled control

single assignment

treatment purpose

1. Voluntary participation in clinical studies; fully understand, be informed about the study and have signed the informed consent form (ICF) ; willingness to follow and ability to complete all trial procedures.
2. Male or female aged >= 18 years at the time of signing the ICF.
3. Histologically or cytologically diagnosed with ES-SCLC (according to the Veterans Administration Lung Study Group staging system).
4. No prior systemic therapy for ES-SCLC (including systemic chemotherapy, molecular targeted therapy, biological therapy, and other investigational therapies, etc.).
5. Patients who have received chemoradiotherapy for previous limited stage SCLC must be treated with curative intent and have a treatment-free interval of at least 6 months from the last course of chemotherapy, radiotherapy, or chemoradiotherapy to the diagnosis of extensive stage SCLC.
6. At least one measurable lesion as assessed by the IRRC according to RECIST 1.1 within 4 weeks prior to first dose.
.
7. Prior antineoplastic therapy must have been >= 2 weeks from the first dose in this study with treatment-related AEs resolved to NCI-CTCAE Grade =< 1 (except for Grade 2 alopecia).
8. An ECOG PS score of 0 or 1.
9. An expected survival >= 12 weeks.
10. Subjects with prior denosumab use that can and agree to switch to bisphosphonate therapy for bone metastases starting prior to first dose and throughout treatment.

1. Histologically or cytologically confirmed mixed SCLC.
2. Other active malignancies within 5 years or at the same time. Localized tumors that have been cured, such as basal cell carcinoma, squamous-cell skin cancer, superficial bladder cancer, prostate carcinoma in situ, cervical cancer in situ and breast cancer in situ are acceptable.
3. Patients who are preparing for or have received an organ or bone marrow transplant.
4. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently). Patients with indwelling catheters are allowed regardless of drainage frequency.
5. Patients with known or documented active CNS metastases and/or carcinomatous meningitis at screening. However, the following subjects are allowed to be enrolled: 1) Subjects with asymptomatic brain metastases (i.e., no progressive central nervous system symptoms caused by brain metastases, no requirement for corticosteroids, and lesion size =< 1.5 cm) may be included, but are required to receive regular brain imaging as a site of lesion. 2) Subjects with treated brain metastases which have been stable for at least 2 months (as confirmed by 2 radiological examinations at least 4 weeks apart after treatment of brain metastases), with no evidence of new or enlarging brain metastases, and with discontinued steroids 3 days prior to study drug administration. (Stable brain metastases here should be confirmed before the first dose of the study drug.).
6. Subjects with spinal cord compression that has not been radically treated with surgery and/or radiotherapy.
7. Patients with myocardial infarction within half a year before the first dose of the study drug, poorly controlled arrhythmia (including QTc intervals >= 450 ms for males and >= 470 ms for females) (QTc intervals are calculated by Fridericia's formula).
8. Class III to IV cardiac insufficiency according to NYHA classification or a left ventricular ejection fraction < 50% by cardiac color Doppler.
9. Subject has uncontrolled or symptomatic hypercalcemia (> 1.5 mmol/L ionized calcium or calcium > 12 mg/dL or corrected serum calcium > ULN).
10. Subject with peripheral neuropathy >=Grade 2 by CTCAE.
11. Human immunodeficiency virus (HIV) infection, positive test for HIV antibody.
12. Active or latent pulmonary tuberculosis.
13. Subjects with previous and concurrent interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-related pneumonitis and severe impaired pulmonary function that may interfere with the detection and management of suspected drug-related pulmonary toxicity, as judged by the investigator.
14. Hepatitis B (positive test for HBsAg or HBcAb and positive test for HBV-DNA) or Hepatitis C (positive tests for HCV antibody and HCV-RNA). Hepatitis B and C coinfection (positive test for HBsAg or HBcAb and positive test for HCV antibody).
15. Known active or suspected autoimmune diseases. Subjects in a stable state with no need for systemic immunosuppressant therapy are allowed to enroll.
16. Have received treatment with live vaccines within 28 days prior to the first administration. Subjects may receive inactivated viral vaccines for seasonal influenza but may not receive live attenuated influenza vaccines via intranasal route.
17. Subjects requiring treatment with systemic corticosteroids (> 10 mg/day prednisone efficacy dose) or other immunosuppressive drugs within 14 days prior to the first dose or during the study. However, in the absence of active autoimmune disease, subjects are allowed to use topical or inhaled steroids and adrenal hormone replacement therapy at doses equivalent to =< 10 mg/day of prednisone efficacy.
18. With any active infection requiring systemic anti-infective treatment within 14 days prior to the administration of the investigational product.
19. Major surgery within 28 days prior to the first dose of the study drug, defined as:
surgeries requiring at least 3 weeks of recovery to be able to receive treatment in this study.
20. Radical radiation therapy within 3 months prior to study medications.
21. The subject has previously received other antibodies/drugs against immune checkpoints, such as PD-1, PD-L1, CTLA4, etc.
22. Participation in any other ongoing clinical studies, or less than 14 days from the end of the previous clinical study treatment to the start of this trial.
23. Known history of severe allergy to any monoclonal antibody.
24. Known hypersensitivity to carboplatin or etoposide.

Both

Extensive Stage Small Cell Lung Cancer

A combination of HLX10 + carboplatin + etoposide shall be administered in a 3-week treatment cycle; carboplatin and etoposide are administered for a maximum of 4 cycles. HLX10 is 4.5 mg/kg, administered on Day 1 of each cycle, once every 3 weeks .Etoposide is 100 mg/m2, IV infusion, on Days 1, 2, and 3 of each cycle. Carboplatin is AUC = 5, dose of carboplatin (mg) = target AUC X ((CrCl (mL/min) + 25)), up to a dose of 750 mg, IV infusion, on Day 1 of each cycle.

Response (CR or PR) rate at week 24

- Overall survival (OS)
- 12 - month OS rate
- PFS
- 6 -month PFS rate
- 12 - month PFS rate
- Objective response rate (ORR)
- Response (CR or PR) rate at week 24
- Response (CR or PR) rate at week 48
- Duration of response (DOR)
- The proportion of patients with a response lasting at least 24 weeks, and 48 weeks
- Adverse events (AEs) (including serious adverse events (SAEs)), laboratory tests (routine blood test, blood chemistry, coagulation function, urinalysis, myocardial function and thyroid function), 12-lead electrocardiogram (12-lead ECG), vital signs, and physical examination, etc.
- Observed PK concentrations and PK parameters of HLX10 in serum
- HLX10 anti-drug antibody (ADA) positive rate
- Quality of life assessment

Mar. 17, 2025

No

none