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

Phase 1b/2 Study of AK104 (Anti-PD1/CTLA4 Bispecific Antibody) in Combination With Etoposide and Carboplatin Plus Low-dose Radiotherapy (LDRT) for the First-line Treatment of Patients With Extensive Stage Small Cell Lung Cancer

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.

Study Overview

• Status: Active, not recruiting
• Conditions: SCLC, Extensive Stage
• Intervention / Treatment: Drug: Carboplatin; Drug: Etoposide; Drug: AK104; Radiation: low-dose radiotherapy

Detailed Description

This trial aims to assess the safety and efficacy of a new therapeutic strategy that combines to low-dose radiotherapy combination With AK104 plus etoposide and carboplatin/cisplatin.

• Study Type: Interventional
• Enrollment (Estimated): 57
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • West China Hospital, Sichuan University
    • Chengdu, Sichuan, China, 610000
      • China West Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 18 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.

Exclusion Criteria:

• 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.
• Currently receiving the treatment of hepatitis B virus infection..
• Received approved or under development systematic anti-tumor therapy within 28 days before enrollment
• Previously received immune checkpoint agonists (antibodies to CD137 targets) or immune checkpoint inhibitors (such as anti-PD-1 antibodies, anti-PD-L1 antibodies, anti-CTLA-4 antibodies, etc.) , immune cell therapy and other treatment of any immune mechanism for tumors
• Treatment with systemic immunosuppressive medications within 1 week prior to enrollment..
• Known allergies or intolerant to test drugs or their excipients; or a known history of severe hypersensitivity reactions to other antibodies.
• Women who are pregnant (positive pregnancy test before medication) or breastfeeding.
• Received chest radiation therapy prior to the first dose.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: LDRT+AK104+chemotherapy; 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: Carboplatin; 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).; Other Names: Chemotherapy; Drug: Etoposide; 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).; Other Names: Chemotherapy; Drug: AK104; IV infusion; Other Names: Cadonilimab; Radiation: low-dose radiotherapy; 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).; Other Names: LDRT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	ORR is proportion of subjects with complete response(CR) or partial response(PR). Tumor responses will be evaluated according to RECIST 1.1 criteria. Patients with no tumor assessment after baseline will be classified as non-responders.	Interval between the date of enrollment and the date of death from any cause, up to a maximum of 18 months.
Disease control rate (DCR)	DCR is defined as the proportion of subjects with CR, PR, or SD (subjects achieving SD will be included in the DCR if they maintain SD for ≥8 weeks) based on RECIST V1.1	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)	PFS is defined as the time from the date of first dosing till the first documentation of disease progression (per RECIST v1.1) assessed by the investigator or death due to any cause (whichever occurs first)	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)	PFS-6 is defined as patient outcomes were evaluated at diagnosis and in the subsets of patients achieving progression-free status at 12 months from diagnosis.	12 months.
Overall survival (OS)	OS is defined as the time from randomization to death.	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)	OS-12 is defined as patient outcomes were evaluated at diagnosis and in the subsets of patients survival at 12 months from diagnosis.	12 months
OS Rates at 24 Months ( OS-24)	OS-24 is defined as patient outcomes were evaluated at diagnosis and in the subsets of patients survival at 24 months from diagnosis.	24 months
Number of participants with adverse events (AEs)	An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product. temporally associated with the use of study treatment, whether or not considered related to the study treatment	From the subject signs the Informed Consent Form to 90 days after the last dose of study treatment or initiation of other anti-tumor therapy

Collaborators and Investigators

• Sponsor: Sichuan University

Study record dates

Study Major Dates

• Study Start (Actual): May 16, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: June 19, 2024
• First Submitted That Met QC Criteria: June 26, 2024
• First Posted (Actual): June 27, 2024

Study Record Updates

• Last Update Posted (Actual): April 29, 2026
• Last Update Submitted That Met QC Criteria: April 23, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Organic Chemicals; Therapeutics; Hydrocarbons; Hydrocarbons, Cyclic; Carbohydrates; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Glucosides; Glycosides; Coordination Complexes; Etoposide; Carboplatin; Radiotherapy; Drug Therapy
• Other Study ID Numbers: AK104-IIT-027

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No