A Multicenter, Single-arm, Open-label Study Evaluating the Safety and Efficacy of AK112 Combined With Chemotherapy as First-line Treatment for Non-squamous NSCLC Patients With BRAIN Metastases and Negative Driver Genes (IVO BRAIN)

NCT06684873 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: AK112-IIT-C-M-0005
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 1

Brief Summary

A multicenter, single-arm, open-label study evaluating the safety and efficacy of AK112 combined with chemotherapy as first-line treatment for non-squamous NSCLC patients with BRAIN metastases and negative driver genes

Conditions

NSCLC; Brain Metastasases

Outcome Measures

Primary Outcomes (1)

• iPFS

  iPFS was defined as the time from the date of initiation of firstline setting to the date of intracranial progression or death and was censored at the date of the last tumor assessment (when carried out)

  iPFS was defined as the time from the date of initiation of firstline setting to the date of intracranial progression or death and was censored at the date of the last tumor assessment (when carried out)

Study Arms (1)

AK112 combined with chemotherapy

EXPERIMENTAL

AK112 combined with chemotherapy

Drug: AK112 Injection

Interventions

AK112 Injection DRUG

AK112 injection plus chemotherapy was administered to all eligible patients

AK112 combined with chemotherapy

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• The subjects voluntarily participated in the clinical study and had not received any systemic anti-tumor treatment (including any chemotherapy, targeted therapy, immunotherapy, etc.)
• Male or female subjects aged 18-75 years (including the cutoff) at the time of signing the ICF
• patients with histopathologically or cytologically confirmed stage IV non-squamous non-small cell lung cancer (nsqNSCLC) with brain metastases
• Patients were required to provide a genetic testing report that showed negative driver genes, i.e., no EFGR sensitive gene mutation, no ALK or ROS1 gene fusion, no BRAF V600E sensitive gene mutation, and no RET gene fusion
• \. If not, qualified tumor tissue or blood should be provided for genetic testing. 5) MRI confirmed brain parenchymal metastasis, with ≥3 brain lesions
• : Or patients with 1-2 brain lesions who are not suitable for local treatment or refuse local treatment. At least one measurable brain lesion had to be at least 5mm in diameter. 6) For asymptomatic brain metastases or those with controlled intracranial hypertension after treatment with dehydration, medication could be continued at enrollment or during the study to maintain symptom stability
• \) At least one measurable target lesion as assessed by investigator according to RECIST v1.1 within 4 weeks before the first dose
• \) ECOG PS score of 0-1
• \) predicted survival time ≥12 weeks
• \) good vital organ function
• \) Female subjects must have a negative serum pregnancy test within 3 days before treatment, agree to use effective contraception during and after treatment for 6 months, and refrain from breastfeeding during treatment
• : Male patients provided consent to use contraception during treatment.

You may not qualify if:

• : any active infection requiring systemic anti-infective therapy within 14 days before the first dose
• \) myocardial infarction with uncontrolled arrhythmia (including QTc interval ≥450 ms in men and ≥470 ms in women) within 6 months before the first dose (QTc interval was calculated with Fridericia's formula)
• : Or grade III-IV cardiac dysfunction according to the New York Heart Association (NYHA) standard or left ventricular ejection fraction \<50% by echocardiography
• \) subjects with ≥ grade 2 CTCAE peripheral neuropathy
• \) subjects had uncontrolled or symptomatic hypercalcemia (\>1.5 mmol/L ionized calcium or calcium \>12 mg/dL or corrected serum calcium \>ULN)
• \) subjects with previous or screening history of interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-related pneumonia, or severely impaired pulmonary function, which may interfere with the detection and treatment of suspected drug-related pulmonary toxicity according to the investigator's judgment
• \) untreated active hepatitis B subjects (HBsag-positive and HBV-DNA \> 1000 copies /mL (200 IU/mL) or higher than the lower limit of detection, whichever is higher) and, for those with hepatitis B, required to receive anti-HBV treatment for the duration of the study treatment
• : Active hepatitis C subjects (positive for HCV antibodies and HCV-RNA levels above the lower limit of detection)
• : Or patients with known active syphilis infection (excluding patients with positive heterologous antibody test, negative non-heterologous antibody test and inactive infection confirmed by clinical judgment)
• Or a known history of human immunodeficiency virus (HIV) positivity or screening positive for HIV
• \) the subject has a known active or suspected autoimmune disease. Subjects who were in a stable state and did not require systemic immunosuppressive therapy were allowed to enroll.
• \) Recipients of a live or attenuated vaccine within 28 days before the first dose, or having a plan to receive such vaccine during the study period. However, inactivated virus vaccines for seasonal influenza are permitted
• \) radical radiotherapy or whole brain radiotherapy (WBRT) to the skull within 3 months before the first dose
• \) subjects with spinal cord compression that could not be cured by surgery and/or radiotherapy
• \) patients with deep vein thrombosis, current anticoagulant or platelet therapy, or previous use of antiangiogenic drugs for deep vein thrombosis or severe bleeding

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

Sun Yat-Sen University Cancer Center

Guangzhou, Guangzhou, 510000, China

Location

Related Publications (1)

• Hou X, Li M, Wu G, Feng W, Su J, Jiang H, Jiang G, Chen J, Zhang B, You Z, Liu Q, Chen L. Gefitinib Plus Chemotherapy vs Gefitinib Alone in Untreated EGFR-Mutant Non-Small Cell Lung Cancer in Patients With Brain Metastases: The GAP BRAIN Open-Label, Randomized, Multicenter, Phase 3 Study. JAMA Netw Open. 2023 Feb 1;6(2):e2255050. doi: 10.1001/jamanetworkopen.2022.55050.

  PMID: 36753281 RESULT

Central Study Contacts

likun Chen

CONTACT

+86 13798019964; chenlk@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: senior doctor

Study Record Dates

• First Submitted: November 10, 2024
• First Posted: November 12, 2024
• Study Start: November 2, 2024
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: November 12, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)