Clinical trial NCT06477523: Phase 1b/2 Study of LDRT in Combination With AK104 Plus Chemotherapy as First-line Treatment for ES-SCLC
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: SCLC, Extensive Stage
Lead sponsor: Sichuan University
Sponsor class: OTHER
First posted: 2024-06-27
Enrollment: 57
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of treatment-related adverse events
timeFrame: 48 months
measure: Progression free survival at 6 months (PFS-6)
timeFrame: 6 months
Secondary outcomes:
measure: Disease control rate (DCR)
timeFrame: Interval between the date of enrollment and the date of death due to any cause , up to a maximum of approximately 2 years
measure: Progression free survival (PFS)
timeFrame: 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.
measure: PFS Rates at 12 months (PFS-12)
timeFrame: 12 months.
measure: Overall survival (OS)
timeFrame: 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.
measure: OS Rates at 12 Months (OS-12)
timeFrame: 12 months
measure: OS Rates at 24 Months ( OS-24)
timeFrame: 24 months
measure: Objective Response Rate (ORR)
timeFrame: Interval between the date of enrollment and the date of death from any cause, up to a maximum of 18 months.
measure: Number of participants with adverse events (AEs)
timeFrame: 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
Other outcomes:
Locations:
city: Chengdu
country: China
facility: China West Hospital
state: Sichuan
city: Chengdu
country: China
facility: West China Hospital, Sichuan University
state: Sichuan
Study officials:
References: