Toripalimab Plus Anlotinib for the Maintenance of Extensive Stage Small Cell

NCT06441344 | Not Yet Recruiting Phase 3

• 1 other identifier: SCLC-maintaine
• Study Type: interventional
• Target: 136
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a randomized, open, multicenter Phase III clinical study. A total of 136 participants are planned to be enrolled and randomly assigned to either the experimental group (platinum+etoposide → toripalimab plus anlotinib) or the control group (platinum+etoposide+ toripalimab → toripalimab) in a 1:1 ratio. The primary efficacy measures include PFS, while secondary endpoints include OS, DOR, ORR, DCR, progression free survival at 6 and 12 months, overall survival at 12 and 18 months, health-related quality of life (FACT-L), safety, etc. And in the III clinical study, tissue samples were collected before treatment, and tumor tissue and blood samples were taken from some patients after 3 cycles of maintenance treatment and treatment progression for single-cell sequencing and transcriptome sequencing to verify the underlying mechanism research

Conditions

SCLC; Maintenance Treatment

Keywords

ES-SCLC; Maintenance Treatment; Toripalimab; Anlotinib

Outcome Measures

Primary Outcomes (2)

• progression free survival(PFS)

  The time from the start of randomization until the first occurrence of disease. progression or death from any cause, whichever occurs first.

  5 years from first patient randomized

• overal survival time(OS)

  The time from randomization to death from any cause

  5 years from first patient randomized

Secondary Outcomes (3)

• Adverse events

  Duration of time from the start of treatment to the end of study, assessed up to 5 years

• objective response rate(ORR)

  Duration of time from the start of treatment to the end of study, assessed up to 5 years

• Disease control rate(DCR)

  Duration of time from the start of treatment to the end of study, assessed up to 5 years

Study Arms (2)

platinum+etoposide → toripalimab plus anlotinib

EXPERIMENTAL

The experimental group was given etoposide (100 mg/m2) d1-3+carboplatin (AUC 5 d1)/cisplatin (25 mg/m2)d1-3 Chemotherapy regimen, for patients who have received 4-6 cycles chemotherapy sessions (including PR, CR, SD), they will enter the maintenance treatment phase and receive an oral dose of 12 mg of anlotinib (d1-14) combined with intravenous infusion of toripalimab 240mg for maintenance treatment until progress or intolerable adverse reactions occur or died for other illnesses

Drug: Toripalimab plus Anlotinib

platinum+etoposide+ toripalimab → toripalimab

ACTIVE COMPARATOR

The control group was given etoposide (100 mg/m2) d1-3+carboplatin (AUC 5) d1/cisplatin (25mg/m2)+and toripalimab (240 mg) ,for patients who have received 4-6 cycles chemotherapy sessions (including PR, CR, SD), they will enter the maintenance treatment phase and receive maintenance treatment with toripalimab 240 mg d1 until progress or intolerable adverse reactions occur or died for other illnesses

Drug: Toripalimab

Interventions

Toripalimab plus Anlotinib DRUG

For patients who did not progress after standard chemotherapy, toripalimab plus anlotinib maintenance therapy was used

platinum+etoposide → toripalimab plus anlotinib

Toripalimab DRUG

For patients who did not progress after standard chemotherapy+toripalimab, toripalimab maintenance therapy was used

platinum+etoposide+ toripalimab → toripalimab

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female aged ≥ 18 and\<80 years old.
• The ECOG score is 0-1 points (including 0 and 1 points), and the expected survival period is not less than 3 months.
• Confirmed as small cell lung cancer (SCLC) by histopathology or cytology and diagnosed as extensive after systemic evaluation.
• I have not received first-line treatment for ES-SCLC systemic chemotherapy or immune checkpoint inhibitors in the past.
• Limited stage SCLC progresses to extensive stage SCLC after receiving previous radiotherapy and chemotherapy aimed at cure,at least 6 months of no treatment period is required after the last radiotherapy and/or chemotherapy treatment.
• Patients with previous active brain metastases have stabilized after treatment and do not require immediate or planned brain intervention during the study period Transfer for local treatment.
• According to the criteria for evaluating the efficacy of solid tumors (RECIST v1.1), enrolled patients should have at least one tumor throughout their body The tumor lesion can meet the following requirements: it has not undergone local treatment such as radiotherapy in the past and is at baseline Can be accurately measured, with a baseline maximum diameter of ≥ 10mm (if it is a lymph node, a minimum diameter of ≥ 15mm is required).
• Lesions that have previously received local treatment (radiotherapy or other treatments), if the treatment is completed for at least 6 months If disease progression occurs later, the lesion in the area that has undergone local treatment can be considered a measurable lesion.
• Patients should have sufficient bone marrow reserve function and no liver, kidney, or coagulation dysfunction, and laboratory tests should be conducted
• The value must meet the following conditions:
• Absolute neutrophil count ≥ 1.5 × 109/L, and white blood cell count ≥ 3 × 109/L;
• Platelet count ≥ 100 × 109/L;
• Hemoglobin ≥ 90g/L;
• Serum creatinine (Cr) ≤ 1.5 x Upper limit of normal (ULN) or creatinine clearance rate (CrCl) ≥ 50ml/min (for patients with serum creatinine\>1.5 x ULN);
• If there is no confirmed liver metastasis, AST and ALT ≤ 2.5 × ULN; If there is confirmed liver metastasis, AST,ALT ≤ 5 × ULN;

You may not qualify if:

• Mixed small cell lung cancer diagnosed by histology or cytology;
• A history of severe allergic diseases, severe drug (including unmarketed investigational drugs) allergies, or known adverse reactions to this medication Allergy to any component of the investigational drug: presence of etoposide, platinum based drugs (carboplatin/cisplatin), or anlotinib.Individuals who are contraindicated to the use of anlotide or Toripalimab;
• Previously received treatment with immune checkpoint agonists (such as CD137 agonists) or immune checkpoint inhibitors.Preparation therapy (such as single/dual antibodies against CTLA-4, PD-1, PD-L1, LAG3, etc.) or anti VEGF targeted drugs;
• Need or plan to undergo elective surgical treatment during the trial period;
• Received the following treatments or medications before starting the research treatment:
• Received important organ surgery (excluding puncture) within 28 days before starting the study and treatment Inspection;
• Received attenuated live vaccine within 28 days prior to starting treatment;
• Have used intravenous broad-spectrum antibiotics for at least 7 days within 14 days before starting the study treatment;
• Starting the study on systemic corticosteroids (prednisone\>10) received within 14 days prior to treatment Mg/day or equivalent dose of similar drugs or other immunosuppressive treatments; Except for the following situations External: Treatment with local, ocular, intra-articular, intranasal, and inhaled corticosteroids; short Regular use of glucocorticoids for preventive treatment (such as preventing contrast agent allergies);
• Received palliative radiotherapy for bone metastases within 14 days prior to starting the study treatment;
• Currently, there is spinal cord compression or superior vena cava syndrome;
• Currently, there are clear cases of interstitial lung disease or non infectious pneumonia, except for those caused by local radiotherapy;
• There are brain metastases in the midbrain, pons, medulla oblongata, spinal cord, meninges, and meninges, or symptomatic large brain metastases Brain or cerebellar metastasis (such as manifested as cerebral edema and/or progressive growth); Central nervous system conversion
• Individuals limited to the brain and cerebellum can participate in screening if they meet the following conditions:
• a. Asymptomatic brain metastases (asymptomatic central nervous system progressive symptoms caused by brain metastases, also not necessary) Using corticosteroids or antiepileptic drugs for treatment; b. Symptoms stabilize for at least 2 weeks after radiotherapy for brain metastases, and corticosteroids or antiepileptic drugs are discontinued Drug discontinuation for at least 2 weeks;

Sponsors & Collaborators

• Taizhou Hospital: lead

MeSH Terms

Interventions

toripalimab; anlotinib

Central Study Contacts

Dongqing Lv, Dr.

CONTACT

13867622009; Lvdq@enzemed.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief medical officer

Study Record Dates

• First Submitted: March 19, 2024
• First Posted: June 4, 2024
• Study Start: July 1, 2024
• Primary Completion: May 1, 2026
• Study Completion (Estimated): May 1, 2030
• Last Updated: June 4, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share