Phase 1b/2 Study of LDRT in Combination With AK104 Plus Chemotherapy as First-line Treatment for ES-SCLC

NCT06477523 | Active Not Recruiting Phase 1

• 1 other identifier: AK104-IIT-027
• Study Type: interventional
• Target: 57
• Locations: 1 country
• Sites: 2

Brief Summary

Phase Ib/II, open-label, multicentre study to evaluate the efficacy and safety of low-dose radiotherapy (LDRT) combined with AK104 and chemotherapy as first-line treatment for patients with ES-SCLC.

Conditions

SCLC, Extensive Stage

Outcome Measures

Primary Outcomes (2)

• Incidence of treatment-related adverse events

  The incidence of treatment-related adverse events were measured for determining tolerability and safety. Adverse events (AEs) are evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE, version 5.0). Events of grade 3-5 are defined as moderate and severe adverse events.

  48 months

• Progression free survival at 6 months (PFS-6)

  PFS-6 is defined as patient outcomes were evaluated at diagnosis and in the subsets of patients achieving progression-free status at 6 months from diagnosis.

  6 months

Secondary Outcomes (8)

• Disease control rate (DCR)

  Interval between the date of enrollment and the date of death due to any cause , up to a maximum of approximately 2 years

• Progression free survival (PFS)

  Interval between the date of enrollment and the date of progressive disease, or death due to any cause (whichever occurs first), up to a maximum of 24 months.

• PFS Rates at 12 months (PFS-12)

  12 months.

• Overall survival (OS)

  Interval between the date of enrollment and the date of progressive disease, or death due to any cause (whichever occurs first), up to a maximum of 24 months.

• OS Rates at 12 Months (OS-12)

  12 months

Study Arms (1)

LDRT+AK104+chemotherapy

EXPERIMENTAL

AK104(IV, D1) + Cisplatin (IV, D1)/Carboplatin (IV, D1) +Etoposide (IV, D1-D3) were administrated on a 21-day cycle for four cycles. Concurrent LDRT (15 Gy/5f) were conducted from D1-D5 in the first cycle. Then pts received LDRT and AK104 maintenance until loss of clinical benefit or unacceptable toxicity.

Drug: AK104; Drug: Etoposide; Drug: Carboplatin; Radiation: low-dose radiotherapy

Interventions

AK104 DRUG

IV infusion

Also known as: Cadonilimab

LDRT+AK104+chemotherapy

Etoposide DRUG

Etoposide intravenous infusion was administered at a dose of 100 mg/m\^2 on Days 1, 2, and 3 of each 21-day cycle during the induction phase (Cycles 1-4).

Also known as: Chemotherapy

LDRT+AK104+chemotherapy

Carboplatin DRUG

Carboplatin intravenous infusion to achieve an initial target AUC of 5 mg/mL/min was administered on Day 1 of each 21-day cycle during the induction phase (Cycles 1-4).

Also known as: Chemotherapy

LDRT+AK104+chemotherapy

low-dose radiotherapy RADIATION

The subjects will receive LDRT, from C1D1-C1D5, once a day for 3Gy, until the target dose of 15Gy is achieved (Cycles 1). LDRT treatment for primary/mediastinal positive lymph nodes/metastatic lesions during maintenance therapy (C1D1-C1D5, 15Gy).

Also known as: LDRT

LDRT+AK104+chemotherapy

Eligibility Criteria

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

You may qualify if:

• to 80 years old.
• Be able and willing to provide written informed consent and to comply with all requirements of study participation (including all study procedures).
• Histologically or cytologically confirmed diagnosis of ES-SCLC per the Veterans Administration Lung Study Group (VALG) staging system.
• No prior treatment for ES-SCLC.
• Measurable disease, as defined by RECIST v1.1.
• Eastern Cooperative Oncology Group performance status ≤ 1.
• Life expectancy ≥ 3 months.
• Adequate hematologic and end-organ function.
• All female and male subjects of reproductive potential must agree to use an effective method of contraception, as determined by the Investigator, during and for 120 days after the last dose of study treatment.

You may not qualify if:

• Symptomatic or actively progressing Central nervous system metastases.
• Uncontrolled carcinomatous meningitis.
• Uncontrolled severe cancer pain
• Uncontrolled pleural effusion, pericardial effusion or ascites requiring recurrent drainage procedures (once a month or more frequently).
• Uncontrolled or symptomatic hypercalcemia.
• History of autoimmune disease.
• History of idiopathic pulmonary fibrosis, organizing pneumonia (such as bronchiolitis obliterans), drug-induced pneumonia, or idiopathic pneumonia, or evidence of active pneumonia on chest computed tomography (CT) during screening.
• Active Tuberculosis infection.
• Significant cardiovascular disease.
• Major surgical procedure within 28 days prior to enrollment or anticipation of need for major surgical procedure during the course of the study.
• Known additional malignancy that is progressing or requires active treatment.
• Active infection requiring systemic therapy
• Prior allogenic bone marrow transplantation or solid organ transplant.
• Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the participant at high risk for treatment complications.
• Receipt of live attenuated vaccination within 4 weeks prior to the first dose of study treatment, or plan to receive live attenuated vaccine during the study.

Sponsors & Collaborators

• Sichuan University: lead

Study Sites (2)

China West Hospital

Chengdu, Sichuan, 610000, China

Location

West China Hospital, Sichuan University

Chengdu, Sichuan, 610041, China

Location

MeSH Terms

Interventions

Etoposide; Drug Therapy; Carboplatin; Radiotherapy

Intervention Hierarchy (Ancestors)

Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Therapeutics; Coordination Complexes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Doctor of Oncology

Study Record Dates

• First Submitted: June 19, 2024
• First Posted: June 27, 2024
• Study Start: May 16, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2027
• Last Updated: April 29, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)