This study has been transitioned to CTIS with ID 2024-515047-31-00 check the CTIS register for the current data. Primary objective:- To evaluate the anti-tumor efficacy of HLX10 in combination with chemotherapy and concurrent radiotherapy in…
ID
Source
Brief title
Condition
- Respiratory tract neoplasms
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Overall survival (OS): OS is defined as a period from randomization through
death from any cause.
Secondary outcome
- Progression-free survival (PFS): PFS is defined as a period from
randomization initiation through the first objective PD or death (on account of
any cause without PD) as assessed by the investigator per RECIST v1.1
- Objective response rate (ORR): ORR is defined as the proportion of subjects
who have the best response of complete response (CR) or partial response (PR)
as assessed by the investigator according to RECIST 1.1.
- Duration of remission (DOR): DOR is defined as the period from the first
recording of response (CR or PR) to the first recording of progressive disease
or death (whichever occurs first) as assessed by the investigator according to
RECIST 1.1. Response termination date should be consistent with the date of PD
or death from any cause for the PFS endpoint as assessed per RECIST v1.1
- 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
- Quality of life assessment
- Serum HLX10 concentration
- HLX10 anti-drug antibody/neutralizing antibody (ADA/NAb)
- Relationship between PD-L1 expression in tumor tissuesand efficacy
Background summary
Small cell lung cancer (SCLC) is a kind of the lung cancer and accounts for
about 15-20% of lung cancer. The disease progresses rapidly with SCLC. SCLC is
divided into two stages, including limited-stage (LS-SCLC) and extensive-stage
(ES-SCLC) small cell lung cancer. Currently, surgery, chemotherapy and
radiotherapy are the primary treatment for LS-SCLC. However, surgery is only
applicable for a few patients with early SCLC. For patients with inoperable
LS-SCLC, concurrent chemotherapy and radiotherapy is the standard treatment
regimen.
Based on the considerable benefits of PD-1/PD-L1 inhibitors in patients with
tumors, Shanghai Henlius Biotech, Inc. independently developed an innovative
PD-1 targeted monoclonal antibody, HLX10. Existing clinical data demonstrates
that HLX10 is confirmed safe and tolerable by the first-in-human phase I study
for patients with advanced solid tumors and other clinical studies for patients
with malignant solid tumors. Preliminary efficacy of HLX10 was observed in some
patients with advanced solid tumors in the first-in-human phase I clinical
study (HLX10-001). The safety and efficacy of HLX10 will be further evaluated
in clinical studies.
Based on the existing pre-clinical and clinical study results, Shanghai Henlius
Biotech, Inc. intends to conduct a phase III clinical study in patients with
LS-SCLC who have never received any treatment for LS-SCLC, to evaluate the
efficacy and safety of HLX10 in combination with chemotherapy
(carboplatin/cisplatin-etoposide) and concurrent radiotherapy.
Study objective
This study has been transitioned to CTIS with ID 2024-515047-31-00 check the CTIS register for the current data.
Primary objective:
- To evaluate the anti-tumor efficacy of HLX10 in combination with chemotherapy
and concurrent radiotherapy in subjects with LS-SCLC
Secondary objectives:
- To evaluate the safety of HLX10 in combination with chemotherapy and
concurrent radiotherapy in subjects with LS-SCLC
- To evaluate the pharmacokinetics (PK), immunogenicity, and biomarkers
Study design
This study is a randomized, double-blind, placebo-controlled, phase III
clinical study to evaluate the anti-tumor efficacy and safety of HLX10 in
combination with chemotherapy and concurrent radiotherapy in subjects with
LS-SCLC.
Subjects will be randomized 1:1 to Arm A or Arm B:
- Arm A (HLX10): HLX10 + chemotherapy (carboplatin/cisplatin-etoposide) +
radiotherapy
- Arm B (control): placebo + chemotherapy (carboplatin/cisplatin-etoposide) +
radiotherapy
The 4 stratification factors include ECOG PS (0 or 1), staging (I/II or III),
radiation fraction (bid or qd), and region (Asia or non-Asia).
After screening, subjects meeting the inclusion criteria and not meeting the
exclusion criteria will be enrolled. All enrolled subjects will receive HLX10
or placebo in combination with chemotherapy Q3W and concurrent radiotherapy.
Prophylactic cranial radiotherapy after chemoradiotherapy is highly recommended
for patients with CR/PR, SD at the discretion of the investigator.
The said regimen should be continued until progressive disease (determined by
the investigator according to RECIST1.1), toxicity intolerance, withdrawal of
informed consent, death, loss to follow-up, or other reasons specified in the
protocol (whichever occurs first). Subjects who discontinue the study treatment
will immediately enter the follow-up period
This study is divided into three stages: screening (28 days), treatment (until
disease progression, intolerable toxicity, withdrawal of informed consent,
death, loss to follow-up or other reasons specified in the protocol, whichever
occursfirst), and follow-up (including safety follow-up period and survival
follow-up period).
Intervention
One treatment cycle lasts for 3 weeks (21 days). The patient will be treated on
Day 1 of the first 4 cycles with study medication (HLX10) or placebo in
combination with chemotherapy for up to 16 months. The patient will receive
concurrent radiotherapy starting on Day 1 of cycle 2, HLX10 or placebo alone
(without chemotherapy) will be administrated since Day 1 of cycle 5 and
following cycles. The route of administration for HLX10 and placebo is
intravenous infusion and the dose of HLX10 is 300 mg. Administration of the
investigational drug or placebo will be completed within 30 to 90 min.
For this study, we will have 2 groups:
- Group 1 (the experiment group). The people in this group will get HLX10 in
combination with chemotherapy and concurrent radiotherapy.
- Group 2 (the control group). The people in this group will get placebo in
combination with chemotherapy and concurrent radiotherapy.
A draw will decide which treatment the patient is given. The chances of
receiving HLX10 or placebo in combination with chemotherapy and concurrent
radiotherapy are 50% (1 in 2).
Study burden and risks
The schedule of activities, which summarizes the frequency and timing of the
various measurements, can be found in the protocol (pages 25-31).
Discomforts and risks associated with participation:
Medicinal product /
Side effects whereof the investigator should be immediately notified:
hypersensitivity, encephalitis, myocarditis, polymyositis, rhabdomyolysis,
toxic epidermal necrolysis, Stevens-Johnson syndrome and renal failure.
The following side effects are common: Skin toxicity (mainly rashes and
pruritus (30-40%)), Diarrhea and/or colitis (8-19%), Fatigue (16-24%),
Immune-related hepatitis (liver inflammation) (5%), Hypothyroidism (4-10%),
Hyperthyroidism (increased secretion of thyroid hormones) (4%), Hypophysitis
(pituitary gland inflammation) (1%), Type I diabetes mellitus (carbohydrate
metabolism disorder), Immune-related pneumonitis (pulmonary inflammation),
Sarcoidosis (a chronic disease with unknown cause that is characterized by
nodules in the lungs, liver, lymph nodes, and salivary glands) and Rheumatoid
arthritis (joint inflammation).
The following side effects are less frequent: cardiovascular adverse events,
nephritis, encephalopathy, leukodystrophy, posterior reversible encephalopathy
syndrome, peripheral motor and sensory neuropathy, uveitis, episcleritis,
blepharitis, blurred vision, acute cholangitis and acute pancreatitis.
The medicinal product can also have side effects that are not known about at
the moment.
The side effects of carboplatin include:
- Hematologic toxicity, including myelosuppression (decreased bone marrow
activity, resulting in reduced blood cell production).
- Gastrointestinal toxicity, including nausea, vomiting, abdominal pain,
diarrhea, constipation, and decreased appetite.
- Nephrotoxicity, including blood urea nitrogen and creatinine increased (two
markers used to measure renal functions).
- Hypersensitivity, including rashes, fever, pruritus, urticaria (a skin
disease characterized by red itchy or white protruding plaques), erythema,
bronchospasms (sudden contraction of bronchial wall muscles, resulting in
dyspnea), and hypotension (blood pressure decreased).
- Ototoxicity, including hearing loss and tinnitus (buzzing, hissing, or
roaring sounds in ears).
- Neurotoxicity, including weakened deep tendon reflexes (sudden uncontrollable
muscle movements) and paresthesia (abnormal or uncomfortable sensations in the
organs, body parts, or skin).
- Others, including hepatic function abnormal, hypogeusia (decreased sense of
taste), alopecia (hair loss), fever, and chills. Side effects occur in the
respiratory system, cardiovascular system, mucosa and skin, genitourinary
system, and musculoskeletal system.
The side effects of cisplatin include:
- Nephrotoxicity, including blood urea nitrogen and creatinine increased,
hematuria.
- Gastrointestinal toxicity, including decreased appetite, nausea, vomiting,
diarrhea.
- Hematologic toxicity, including white blood cell count decreased and platelet
count decreased.
- Ototoxicity, including tinnitus and hearing loss.
- Neurotoxicity, including peripheral nerve damage, manifested as ataxia,
myalgia, paresthesia in extremities.
- Anaphylaxis, including increased heart rate, blood pressure decreased,
dyspnea, facial edema.
- Others, muscle cramps, hypomagnesemia, cardiac arrhythmias, and so on.
The side effects of etoposide include:
- Myelosuppression, including platelet count decreased and white blood cell
count decreased.
- Decreased appetite, nausea, vomiting, and stomatitis (oral inflammation).
- Hypersensitivity, including hypotension and laryngospasm (closure of the
larynx, blocking air flow into the lungs).
The side effects of radiotherapy include:
- Radiation pneumonitis.
- Radiation esophagitis.
- Decreased appetite, nausea, and vomiting.
- Myelosuppression, including platelet count decreased and white blood cell
count decreased.
- Pigmentation.
- Dermatitis and skin damage.
Pregnancy and breastfeeding:
Women who are pregnant or breastfeeding cannot take part in this study. Women
should also not get pregnant during the study and for at least 6 months after
the last administration of the investigational product. Males with a female
partner need to make sure that she cannot become pregnant with his child for at
least 6 months after the last administration of the investigational product.
Blood sampling: Discomfort (including pain), bleeding, or bruises, small blood
scabs, or swelling (including redness) at the site for blood sampling may be
experienced. In rare cases, lipothymia or localised infection may occur.
Tumor biopsy: If a tumor biopsy is necessary as part of the screening,
discomfort or pain during the procedure may be felt. Bleeding or temporary
discomfort may occur at the tumor biopsy site. If anesthesia is performed
during tumor biopsy, anesthetic complications may occur.
Electrocardiography: During the examination, the patient is required to lie
flat for 5-10 minutes. The investigator will place several electrodes on the
skin of the chest, wrists, and ankles to record the electrophysiological
activities of the heart. The patient may feel cold or mild discomfort on the
skin when the electrodes are placed and removed.
Echocardiography: During the examination, the patient is required to lie flat
for 10-15 minutes. The investigato will place an echocardiography probe on the
skin surface in front of the heart. The patient may feel cold once the probe is
placed on the skin surface and mild discomfort from the compression of the
chest wall. A very small minority of people may be allergic to the coupling
agent on the ultrasonic probe.
Blood pressure: After the patient has rested for 10 minutes in a sitting
position, an inflatable cuff will be placed on the arm and a device will be
used to measure the blood pressure. The patient may experience mild discomfort
in the arm when the cuff is inflated.
Imaging examination (CT or MRI): CT uses X-rays for scanning and image
acquisition. While as a consequence of repeated CT scans, radiation accumulates
over time, and long-term accumulation of low-dose radiation may result in
cancer. However, the dosage and frequency at which CT scanning poses a health
risk remain unclear, and no method is available for accurate prediction.
Magnetic resonance imaging (MRI) uses extremely strong magnets to excite atoms
in the human body. The excited atoms can be detected by a scanner to produce an
image of the scanned object. The patient cannot have an MRI if (s)he has a
ferromagnetic metal implant that may be displaced or heated by magnetism.
Similarly, the patient should not undergo an MRI if (s)he has an implanted
pacemaker. In addition, the patient may feel uncomfortable when required to lie
in a semi-enclosed space in the device for an extended period of time (about 30
to 40 minutes) during the MRI scan.
Bone scan: During the scan, a contrast agent is injected into the vein to help
identify the lesions. The discomfort and risks related to contrast agent
injection in the bone scan are similar to those in the CT scan.
Contrast agent used for imaging examination: The contrast agent may cause such
side effects as nausea, vomiting, headache, pruritus, skin redness, rashes, or
welts, asthma, abnormal heart rhythm, blood pressure increased or decreased,
and shortness of breath. In rare cases, it may cause dyspnea, standstill
cardiac, laryngeal edema or swelling in other body sites, convulsions,
significant hypotension, or even death in severe circumstances. The contrast
agent may cause deterioration of renal functions in patients with renal
insufficiency. A radioactive contrast agent is required during a bone scan. The
bone scan involves a small dose of radiation from the contrast agent, and your
risk of exposure to radiation is low.
Kagnan Road, Pilot Free Trade Zone, PRC No 220, Complex Building, Room 330
Shanghai 200233
CN
Kagnan Road, Pilot Free Trade Zone, PRC No 220, Complex Building, Room 330
Shanghai 200233
CN
Listed location countries
Age
Inclusion criteria
- Patients must be willing to voluntarily participate in this clinical study
and provide written ICF
- Male or female aged >=18 years
- Histologically diagnosed with SCLC
- Diagnosed with LS-SCLC (Stage I-III of the AJCC 8th edition of the cancer
staging) which can be safely treated with curative radiation doses
- At least one measurable lesion as assessed by an investigator as per RECIST
v1.1 within 4 weeks prior to randomization
- Patient must provide tumor tissues that met requirements for assay of PD-L1
expression
- ECOG PS 0 or 1
- Expected survival of at least 6 months
- Laboratory tests verified sufficient organ and marrow function without
abnormalities in haematopoietic function or cardiac, hepatic or renal function
or immunodeficiency within 7 days prior to randomization
- Women of childbearing potential must be tested negative for serum/urine
pregnancy test within 7 days prior to randomization and must agree to use
contraception methods with an annual failure rate of < 1% or to remain
abstinent from signing ICF to at least 6 months after last dose of study drug
- Male patients must agree to remain abstinent or take contraceptions measures
during study treatment and for at least 6 months after last dose of the drug
- Previous non-systematic anti-tumor treatment should be completed >= 2 weeks
prior to initiation of the study medication and treatment related AEs have
returned to <= grade 1 based on CTCAE 5.0 (except alopecia grade 2)
Exclusion criteria
- Histologically or cytologically confirmed mixed SCLC
- Subjects suitable for surgery
- previously received systematic anti-tumor treatments for small cell lung
cancer
- Patients with other active malignancies within 5 years or at the same time
(except localized tumors that have been cured)
- Patients preparing for or have received an organ or bone marrow transplant
- Patients with pleural, pericardial effusions, or ascites requiring clinical
intervention
- Patients wtih myocardial infarction and poorly controlled arrhytmia within 6
months prior to the first dose of the IMP
- Class III to IV cardiac insufficiency according to NYHA classification or a
left ventricular ejection fraction < 50% by cardiac color Doppler
- Subject within uncontrolled or symptomatic hypercalcemia
- Patients with peripheral neuropathy >= grade 2 by CTCAE
- Patients with HIV infection and HIV antibody test results are positive
- Patients with active pulmonary tuberculosis
- Subjects with previous and current interstitial pneumonia, pneumoconiosis,
radiation pneumonitis, drug-related pneumonitis and sever impaired pulmonary
function that may interfere with the detection and management of suspected
drug-related pulmonary toxicity as judged by the investigator.
- Hepatitis B or Hepatitis C (patient with hepatitis B who are stable on
antiviral therapy can be enrolled)
- Subjects with known active or suspected autoimmune diseases. Patients 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 first
administration
- subjects requiring treatment with systemic corticosteroids or other
immunosuppressive drugs within 14 days prior to first dose or during the study
(in absence of active autoimmune disease, subjects are allowed to use topical
or inhaled glucocorticosteroids and <= 20 mg./day therapeutic dose of
prednosine for adrenal glucocorticoid replacement therapy).
- Any active infection requiring systemic anti-infective treatment within 14
days prior to the administration of IMP
- have received any major surgery within 28 days prior to the first dose of the
IP
- 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 study less than 28
days from the end of the previous study treatment to the start of this trial
- 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
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EU-CTR | CTIS2024-515047-31-00 |
| EudraCT | EUCTR2022-002226-27-NL |
| ClinicalTrials.gov | NCT05353257 |
| CCMO | NL82997.056.22 |