A phase 3 study to Evaluate the Efficacy and Safety of HLX10 or placebo in Combination With Chemotherapy and Radiotherapy in Patients With Limited-Stage Small Cell Lung Cancer (LS-SCLC)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Shanghai Henlius Biotech Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

28 Aug 2023 → ongoing

Decision date (initial)

2024-09-02

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Shanghai Henlius Biotech, Inc.

External identifiers

EU CT number

2024-515047-31-00

EudraCT number

2022-002226-27

ClinicalTrials.gov

NCT05353257

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacokinetic, Safety

To evaluate the anti-tumor efficacy of HLX10 in combination with chemotherapy and concurrent radiotherapy in subjects with LS-SCLC.

Secondary objectives 2

1. To evaluate the safety of HLX10 in combination with chemotherapy and concurrent radiotherapy in subjects with LS-SCLC.
2. To evaluate the pharmacokinetics (PK), immunogenicity, and biomarkers.

Conditions and MedDRA coding

Patients with Limited-Stage Small Cell Lung Cancer (LS-SCLC) at stage I-III of the AJCC 8th edition of the cancer staging

Study design 1 period

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-002859-PIP01-20

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. 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.
2. Male or female, aged ≥18 years when signing the ICF.
3. Histologically diagnosed with SCLC.
4. 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.
5. With at least one measurable lesion as assessed by investigator as per RECIST v1.1 within 4 weeks prior to randomization.
6. 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.
7. ECOG PS of 0 or 1.
8. Expected survival of at least 6 months.
9. 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.
10. 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
11. 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.
12. 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).

Exclusion criteria 28

1. Histologically or cytologically confirmed mixed SCLC.
2. Subjects suitable for surgery. Subjects who are suitable for surgery but refuse surgical treatment can be included.
3. Patients who have previously received systematic anti-tumor treatments for small cell lung cancer, including but not limited to radiotherapy, chemotherapy, and immunotherapy.
4. 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.
5. Patients who are preparing for or have received an organ or bone marrow transplant.
6. Patients with pleural, pericardial effusions, or ascites requiring clinical intervention.
7. 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.
8. Class III to IV cardiac insufficiency according to NYHA classification or an 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. Patients with peripheral neuropathy ≥ grade 2 by CTCAE.
11. Patients with human immunodeficiency virus (HIV) infection, and HIV antibody test results are positive.12. Patients with active pulmonary tuberculosis.
12. Patients with active pulmonary tuberculosis.
13. 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.
14. 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.
15. 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.
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 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.
18. With any active infection requiring systemic anti-infective treatment within 14 days prior to the administration of the investigational product.
19. 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.
20. The subject has previously received other antibodies/drugs against immune checkpoints, such as PD-1, PD-L1, CTLA4, etc.
21. 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.
22. Subjects with known history of severe allergy to any monoclonal antibody.
23. Subjects with known anaphylaxis to carboplatin/cisplatin or etoposide.
24. Pregnant or lactating women.
25. Subjects with a known history of psychotropics substance abuse or drug abuse.
26. In the judgment of the investigator, subjects who have any other factors that may lead to a premature discontinuation.
27. Subjects expected to require surgical resection during the study.
28. Primary tumor/lymph node too large for planned radiotherapy.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Overall survival (OS)
2. Progression-free survival (PFS) [assessed by the Blinded Independent Central Review (BICR) as per RECIST v1.1]

Secondary endpoints 8

1. Objective response rate (ORR) (assessed by the BICR and investigator as per RECIST 1.1)
2. Duration of response (DOR) (assessed by the BICR and investigator as per RECIST 1.1)
3. Adverse events (AE) (including serious adverse events (SAE))laboratory tests (hematology, blood chemistry, coagulation function, urinalysis, thyroid function, and cardiac function), 12-lead electrocardiogram (12-lead ECG), vital signs, and physical examination
4. Quality of life assessment
5. Serum HLX10 concentration
6. HLX10 anti-drug antibody/neutralizing antibody (ADA/NAb)
7. Relationship between PD-L1 expression in tumor tissuesand efficacy
8. PFS assessed by the investigator as per RECIST v1.1

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Shanghai Henlius Biotech Inc.

Sponsor organisation

Shanghai Henlius Biotech Inc.

Address

Building 1 Room 901 9th Floor, No 367 Shengrong Road, Shanghai Pilot Free Trade Zone No 367 Shengrong Road Shanghai Pilot Free Trade Zone

City

Shanghai

Postcode

201210

Country

China

Scientific contact point

Organisation

Shanghai Henlius Biotech Inc.

Contact name

Clinical Development

Public contact point

Organisation

Shanghai Henlius Biotech Inc.

Contact name

Clinical Development

Third parties 20

Locations

9 EU/EEA countries · 59 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 177 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

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