Evaluation of HLX10 Combined with Chemotherapy and Radiotherapy in Limited-Stage Small Cell Lung Cancer: A Phase III Randomized, Double-Blind Study

Trial ID: 2024-515047-31-00
Protocol: HLX10-020-SCLC302
Sponsor: Shanghai Henlius Biotech Inc.

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Diseases & Conditions

Small cell lung cancer

Objectives

The primary objective of this study is to evaluate the **anti-tumor efficacy** of HLX10, a recombinant humanized anti-PD-1 monoclonal antibody, in combination with chemotherapy (Carboplatin/Cisplatin-Etoposide) and concurrent radiotherapy in patients with Limited-Stage Small Cell Lung Cancer (LS-SCLC). This objective is clinically relevant as it aims to determine the potential of HLX10 to enhance treatment outcomes in LS-SCLC, a condition characterized by aggressive tumor growth and limited treatment options.

Secondary objectives include:

Evaluating the **safety** of HLX10 when used in combination with chemotherapy and concurrent radiotherapy in subjects with LS-SCLC.
Assessing the **pharmacokinetics (PK)**, immunogenicity, and biomarkers associated with HLX10 treatment.

Participants

The clinical trial involves a total of **362 participants** diagnosed with **Limited-Stage Small Cell Lung Cancer (LS-SCLC)** at stages I-III according to the AJCC 8th edition of cancer staging. The study population includes both male and female subjects aged 18 years and older. Participants were selected based on their histological diagnosis of LS-SCLC, with the condition that it can be safely treated with curative radiation doses. The trial includes individuals with an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1, indicating they are fully active or restricted in physically strenuous activity but ambulatory. Participants are required to have at least one measurable lesion as per RECIST v1.1 criteria and must provide tumor tissues for PD-L1 expression assessment. The study population is characterized by sufficient organ and marrow function, without serious abnormalities in hematopoietic, cardiac, hepatic, or renal function, or immunodeficiency. Lifestyle considerations such as diet and physical activity are not specified, but participants must have completed any previous non-systematic anti-tumor treatment at least two weeks prior to the study and have an expected survival of at least six months. The trial includes a vulnerable population, and both male and female subjects are required to adhere to specific contraception guidelines to prevent drug exposure to embryos during and after the study treatment.

Plans and Procedures

The clinical trial is designed as a **randomized, double-blind, controlled** study to evaluate the anti-tumor efficacy and safety of a **recombinant humanized anti-PD-1 monoclonal antibody (HLX10)** in combination with chemotherapy and concurrent radiotherapy in patients with **limited-stage small cell lung cancer (LS-SCLC)**. The trial will involve participants diagnosed with LS-SCLC at stage I-III according to the AJCC 8th edition of cancer staging. The primary objective is to assess overall survival, while secondary endpoints include progression-free survival, objective response rate, duration of remission, adverse events, quality of life, serum HLX10 concentration, and the relationship between PD-L1 expression and efficacy.

The trial will span an estimated duration from July 31, 2023, to July 19, 2027. Participants will be involved in the study for a maximum treatment period of 65 weeks. The study will commence with a screening visit to confirm eligibility based on inclusion criteria such as age, histological diagnosis, and organ function. Following randomization, participants will receive either HLX10 or placebo via **intravenous infusion** in combination with chemotherapy and radiotherapy. Study visits will be scheduled regularly to monitor treatment response and safety, including assessments of tumor response, laboratory tests, and physical examinations.

Participants will be required to attend follow-up visits to evaluate long-term outcomes and any potential adverse effects. The end-of-study visit will conclude the participant's involvement, ensuring all necessary data is collected. Conditions that may lead to early termination from the study include withdrawal of consent, significant adverse events, or disease progression. The trial is structured to maintain rigorous scientific standards, ensuring the reliability and validity of the results obtained.

Treatment

The clinical trial involves the administration of **Recombinant humanized anti-PD-1 monoclonal antibody (HLX10)**, which is an investigational medication. HLX10 is provided in the form of an **infusion** and is administered via the **intravenous route**. The dosing regimen for HLX10 includes a maximum daily dose of 300 mg, with a total maximum dose of 6600 mg over the course of the treatment period, which spans up to 65 days. The active substance, HLX10, is a protein of other origin, developed by Shanghai Henlius Biotech, Inc. The primary objective of the trial is to evaluate the anti-tumor efficacy of HLX10 in combination with chemotherapy and concurrent radiotherapy in patients with limited-stage small cell lung cancer (LS-SCLC).

In addition to the experimental treatment, the study also includes the use of **HLX10 placebo**. The placebo is utilized to maintain the double-blind nature of the trial, ensuring that neither the participants nor the investigators are aware of the treatment assignments. The placebo is administered in a manner consistent with the active treatment to ensure comparability. The placebo does not contain the active substance and serves as a control to assess the efficacy and safety of the HLX10 treatment.

Participants in the trial will also receive standard-of-care chemotherapy, which includes a regimen of carboplatin or cisplatin combined with etoposide, alongside concurrent radiotherapy. The chemotherapy and radiotherapy are administered according to established medical guidelines for the treatment of LS-SCLC. Compliance with the dosing schedule and administration of both the investigational and non-experimental treatments will be closely monitored throughout the study to ensure adherence to the protocol and to accurately assess the outcomes of the trial.

Efficacy

The efficacy of the investigational product, **HLX10** (Recombinant humanized anti-PD-1 monoclonal antibody), will be assessed in a randomized, double-blind, international multicenter, Phase III clinical trial. The primary endpoint for evaluating efficacy is overall survival (OS) in patients with limited-stage small cell lung cancer (LS-SCLC). Secondary endpoints include progression-free survival (PFS), objective response rate (ORR), duration of remission (DOR), and adverse events (AE), including serious adverse events (SAE). These will be assessed by the investigator according to RECIST v1.1 criteria.

Additional secondary endpoints involve laboratory tests (hematology, blood chemistry, coagulation function, urinalysis, thyroid function, and cardiac function), 12-lead electrocardiogram (12-lead ECG), vital signs, physical examination, quality of life assessment, serum HLX10 concentration, and HLX10 anti-drug antibody/neutralizing antibody (ADA/NAb) levels. The relationship between PD-L1 expression in tumor tissues and efficacy will also be evaluated. The schedule for measuring and collecting these parameters will be aligned with the trial protocol, ensuring systematic data collection and analysis throughout the study duration.

Inclusion and Exclusion Criteria

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Inclusion Criteria

Patients who voluntarily participate in this clinical study; fully understand and have been informed about the study and have signed the ICF; are willing to follow and able to complete all trial procedures.
Male or female, aged ≥18 years when signing the ICF.
Histologically diagnosed with SCLC.
Diagnosed with LS-SCLC (stage 1-3 of the AJCC 8th edition of the cancer staging), which can be safely treated with curative radiation doses.
With at least one measurable lesion as assessed by investigator as per RECIST v1.1 within 4 weeks prior to randomization.
Patients must provide tumor tissues that meet the requirements for assay of PDL1 expression level. Patients are assessed for an evaluable PD-L1 expression category (negative: TPS < 1%, positive: TPS ≥ 1%, or not evaluable/not available) by the central laboratory.
ECOG PS of 0 or 1.
Expected survival of at least 6 months.
Laboratory tests verified sufficient organ and marrow function,without serious abnormalities in haematopoietic function or cardiac, hepatic, or renal function, or immunodeficiency within 7 days prior to randomization.
Female patients must meet one of the following conditions: a. Menopause (defined as no menstruation for at least 1 year with no confirmed cause other than menopause), or b. Surgically sterilized (removal of the ovaries and/or uterus), or c. Fertile, but must: o be tested negative for serum/urine pregnancy test within 7 days prior to the randomization, and o agree to use contraception methods with an annual failure rate of < 1% or to remain abstinent (avoid heterosexual intercourse from signing the ICF to at least 6 months after the last dose of the study drug) (a contraceptive method with an annual failure rate of <1% includes bilateral tubal ligation, male sterilization, correct use of hormonal contraceptives that can inhibit ovulation, hormone-releasing intrauterine devices and copper-containing intrauterine devices or condoms), and o not breastfeed
Male patients must: agree to remain abstinent (avoid heterosexual intercourse) or take contraception measures as follows: male patients with a pregnant partner or a partner of childbearing potential must remain abstinent or use condoms to prevent drug exposure to the embryo during study treatment and for at least 6 months after the last dose of study drug. Periodic abstinence (e.g., contraception based on calendar day, ovulatory phase, basal body temperature, or postovulatory phase) and external ejaculation are ineligible methods of contraception.
Previous non-systematic anti-tumor treatment should be completed ≥2 weeks prior to the initiation of study medication, and treatment related AEs have returned to ≤grade 1 based on Common Terminology Criteria for Adverse Events (CTCAE) 5.0 (except grade 2 hair loss).

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Exclusion Criteria

Histologically or cytologically confirmed mixed SCLC.
Subjects suitable for surgery. Subjects who are suitable for surgery but refuse surgical treatment can be included.
Patients who have previously received systematic anti-tumor treatments for small cell lung cancer, including but not limited to radiotherapy, chemotherapy, and immunotherapy.
Patients with other active malignancies within 5 years or at the same time. Localized tumors that have been cured such as basal cell carcinoma, squamouscell skin cancer, superficial bladder carcinoma, prostate carcinoma in situ, cervical carcinoma in situ, and breast cancer in situ are acceptable.
Patients who are preparing for or have received an organ or bone marrow transplant.
Patients with pleural, pericardial effusions, or ascites requiring clinical intervention.
Patients with myocardial infarction and poorly controlled arrhythmia (including QTc intervals ≥ 470 ms) (QTc intervals are calculated by Fridericia's formula) within 6 months prior to the first dose of the investigational products.
Class III to IV cardiac insufficiency according to NYHA classification or an left ventricular ejection fraction < 50% by cardiac color Doppler.
Subject has uncontrolled or symptomatic hypercalcemia (> 1.5 mmol/L ionized calcium or calcium > 12 mg/dL or corrected serum calcium > ULN).
Patients with peripheral neuropathy ≥ grade 2 by CTCAE.
Patients with human immunodeficiency virus (HIV) infection, and HIV antibody test results are positive.12. Patients with active pulmonary tuberculosis.
Patients with active pulmonary tuberculosis.
Subjects with previous and current 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.
With Hepatitis B (positive test for HBsAg or HBcAb and positive test for HBVDNA) or Hepatitis C (positive tests for HCV antibody and HCVRNA). Subjects with a co-infection of hepatitis B and hepatitis C (tested positive for HBsAg or HBcAb, and positive for anti-HCV antibody). Note: Subjects with hepatitis B who are stable on antiviral therapy (HBVDNA≤ 2500 copies/mL or 500IU/mL) can be enrolled.
Subjects with known active or suspected autoimmune diseases. Subjects in a stable state with no need for systemic immunosuppressant therapy are allowed to be enrolled.
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.
Subjects requiring treatment with systemic corticosteroids (> 10 mg/day therapeutic dose of prednisone) or other immunosuppressive drugs within 14 days prior to the first dose or during the study. However, subjects are allowed to be enrolled under the following conditions: in the absence of active autoimmune disease, subjects are allowed to use topical or inhaled glucocorticoids and ≤ 10 mg/day therapeutic dose of prednisone for adrenal glucocorticoid replacement therapy.
With any active infection requiring systemic anti-infective treatment within 14 days prior to the administration of the investigational product.
Have received any major surgery (defined as surgeries requiring at least 3 weeks of recovery to be able to receive treatment in this study) within 28 days prior to the first dose of the investigational products.
The subject has previously received other antibodies/drugs against immune checkpoints, such as PD-1, PD-L1, CTLA4, etc.
Participation in any other ongoing interventional clinical studies, or less than 28 days from the end of the previous interventional clinical study treatment to the start of this trial.
Subjects with known history of severe allergy to any monoclonal antibody.
Subjects with known anaphylaxis to carboplatin/cisplatin or etoposide.
Pregnant or lactating women.
Subjects with a known history of psychotropics substance abuse or drug abuse.
In the judgment of the investigator, subjects who have any other factors that may lead to a premature discontinuation.
Subjects expected to require surgical resection during the study.
Primary tumor/lymph node too large for planned radiotherapy.

Trial Status by Country

Country	Status	Start of Recruitment	Planned Patients
Austria	Not Recruiting	31 Jul 2023	2
Czechia	Not Recruiting	31 Jul 2023	6
Germany	Not Recruiting	31 Jul 2023	7
Greece	Not Recruiting	31 Jul 2023	27
Hungary	Not Recruiting	31 Jul 2023	4
Latvia	Not Recruiting	31 Jul 2023	8
The Netherlands	Not Recruiting	31 Jul 2023	—
Poland	Not Recruiting	31 Jul 2023	6
Spain	Not Recruiting	31 Jul 2023	46
Netherlands	—	—	5