Non-Small Cell Lung Cancer、EGFR Sensitive Mutation
Conditions
Brief summary
To evaluate the safety and tolerance of MCLA-129 combined with Befotertinib in patients with advanced non-small cell lung cancer with EGFR-sensitive mutations.
Detailed description
This is a phase I study to evaluate the safety, pharmacokinetic characteristics and antitumor activity of anti-EGFR/c-Met bispecific antibody MCLA-129(1500mg Q2W IV or 2000mg Q2W IV) combined with Befotertinib (75 mg once daily for first cycle, then increased to 100 mg once daily, orally) in Patients of advanced non-small cell lung cancer with exon 19 deletion or exon 21 L858R mutation(either alone or in combination with other EGFR mutations).
Interventions
DRUGMCLA-129: 1500mg or 2000mg IV Q2W
Every 28 days is a cycle until disease progression, death, initiation of new anti-tumor treatment, loss of follow-up, or voluntary withdrawal occurs
DRUGBefotertinib: 75 mg or 100 mg Po QD
The initial dose of Befotertinib is 75 mg orally once daily (QD) for one cycle, and then increased to 100 mg orally QD in the absence of CTCAE grade ≥ 2 headache or thrombocytopenia during the first cycle, otherwise maintained to 75 mg orally QD. Every 28 days is a cycle until disease progression, death, initiation of new anti-tumor treatment, loss of follow-up, or voluntary withdrawal occurs.
Sponsors
Betta Pharmaceuticals Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Age from 18 to 75 years. * Histologically or cytologically confirmed locally advanced or metastatic NSCLC that is not suitable for radical surgery or radiotherapy, and harbored EGFR exon 19 deletion or exon 21 L858R mutation( either alone or in combination with other EGFR mutations) in NSCLC assessed by genetic testing. * For Part 1: patients with advanced NSCLC must be progression, or intolerance, or rejected to standard therapy(subjects treated with Befotertinib must be progression of the disease). * For Part 2, each cohort is defined as follows: * Cohort A: Previously diagnosed EGFR-sensitive mutations and no systemic antitumor therapy for locally advanced or metastatic NSCLC. * Cohort B: Advanced NSCLC patients with previously diagnosed EGFR-sensitive mutations and third generation EGFR-TKI resistance. * Cohort C: Advanced NSCLC patients who had previously been diagnosed with EGFR-sensitive mutations and first or second EGFR-TKI resistance. Patients in cohorts B and C must also resistance, or intolerance, or rejection of platinum-containing chemotherapy. •Patients of the dose escalation phase in Part 1 must have evaluable diseases, and others must have measurable diseases as defined in RECIST V1.1 definition. Note: The selected target lesions must meet one of two criteria: 1) no previous local treatment or 2) subsequent progression within the previous local treatment area as determined by RECIST V1.1. * Eastern Cooperative Oncology Group (ECOG) performance status scores are 0-1. * Expected survival is ≥3 months. * With certain organ system functions (without transfusion, use of blood components, or G-CSF support within 14 days before testing), as defined below: oAbsolute neutrophil count (ANC)≥1.5×10\^9/L oPlatelet count (PLT)≥100×10\^9/L oHemoglobin (HB)≥10 g/dL oSerum albumin≥30 g/L oTotal bilirubin≤1.5 times the upper limit of normal (ULN) oAlanine amino transferase ( ALT) and aspartate amino transferase (AST) ≤3×ULN oCreatinine≤1.5×ULN.If creatinine is\>1.5×ULN, creatinine clearance is≥50 mL/min as calculated by Cockcroft-Gault formula, or urinary creatinine clearance≥50 mL/min within 24 hours as measured, the patients can still be enrolled. * Willing and able to follow the trial and follow-up procedures. * Capable of understanding the trial nature and voluntarily signing the written informed consent form.
Exclusion criteria
* Use of certain investigational drug or antineoplastic agent within 14 days or 5 half lives (whichever is longer) before first administration of investigational drug (For drugs with a longer half-life, a maximum of 4 weeks is required from the last administration; 6 weeks for chemotherapy with delayed toxicity, such as Nitroso urea or Mitomycin C). * Execution of large surgery and radiotherapy (except focal palliative radiotherapy at least 2 weeks before first administration) within 4 weeks before first administration. * For the dose extension stage of part 2 and part 2: having previously received systemic anti-tumor therapy exceeding three lines (excluding maintenance therapy). * Previously received EGFR/c-Met bispecific antibody drugs (such as JNJ-61186372, EMB-01, or GB263T) for treatment. * Prior to the first administration of the study drug, previous treatment-related toxic reactions did not alleviate to level 1 or below (CTCAE 5.0 standard), except for hair loss. * With other malignant tumors in the past 3 years, except cancers that have been cured significantly or can be focally cured, e.g. basosquamous carcinoma of skin, carcinoma cervix in situ, or in situ breast carcinoma. * Primary malignant tumor of the central nervous system, meningeal metastasis, or brain metastasis with spinal cord compression, or risk of cerebral hemorrhage, or symptomatic brain metastasis, or unstable brain metastasis requiring steroid and/or dehydration to reduce intracranial pressure 2 weeks before enrollment (subjects with brain metastases who are Asymptomatic or stable for more than 2 weeks after treatment and do not need steroids and/or dehydration to reduce intracranial pressure can be included in the group). * With clinically significant cardiovascular disorder, including but not limited to: * Arterial thromboembolism, deep vein thrombosis or lung embolism diagnosed within 3 month before first administration of the investigational drug. Non- obstructive catheter related clot and other clinically irrelevant thrombosis are not included in the
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose-Limiting Toxicity (DLT) | First 28 days of treatment | To determine the dose-limiting toxicity (DLT) of MCLA-129 combined with Befotertinib in patients of advanced non-small cell lung cancer with EGFR-sensitive mutations in Part 1. |
| Maximum Tolerable Dose (MTD) | First 28 days of treatment | To determine the maximum tolerated dose (MTD) of MCLA-129 combined with Befotertinib in patients of advanced non-small cell lung cancer with EGFR-sensitive mutations in Part 1. |
| Treatment-Emergent Adverse Event (TEAE) in Part 1 | Until 30 days after the last dosing | To evaluate the safety of MCLA-129 combined with Befotertinib in patients of advanced non-small cell lung cancer with EGFR-sensitive mutations in Part 1 in terms of treatment-emergent adverse event (TEAE). |
| Overall Response Rate (ORR) in Part 2 | From date of first treatment every 6 weeks until disease progression, death or withdrawal, whichever came first, approximately 2 years | To evaluate the efficacy of MCLA-129 combined with Befotertinib at RP2CD in patients of advanced NSCLC with EGFR-sensitive mutations in each corhort in Part 2 in terms of overall response rate (ORR) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Anti-Drug Antibody (ADA) in Part 1 and 2 | Until 30 days after the last dosing | To assess the Incidence of anti-drug antibodies in serum blood against MCLA-129 following administration of MCLA-129. |
| Overall Survival (OS) in Part 2 | From date of first treatment every 6 weeks until death or withdrawal, whichever came first, approximately 2 years | To evaluate the efficacy of MCLA-129 combined with Befotertinib at RP2CD in patients of advanced NSCLC with EGFR-sensitive mutations in Part 2 in terms of overall survival (OS). |
| Treatment-Emergent Adverse Event (TEAE) in and 2 | Until 30 days after the last dosing | To evaluate the safety of MCLA-129 combined with Befotertinib in patients of advanced non-small cell lung cancer with EGFR-sensitive mutations in Part 2 in terms of treatment-emergent adverse event (TEAE). |
| Overall Response Rate (ORR) in Part 1 | From date of first treatment every 6 weeks until disease progression, death or withdrawal, whichever came first, approximately 2 years | To evaluate the efficacy of MCLA-129 combined with Befotertinib at RP2CD in patients of advanced NSCLC with EGFR-sensitive mutations in each corhort in Part 1 in terms of overall response rate (ORR). |
| Time to reach maximum concentration [Tmax] | Until 30 days after the last dosing | To evaluate the PK profile of MCLA-129 combined with Befotertinib in patients dvanced NSCLC with EGFR-sensitive mutations in Part 1. |
| Trough concentration [Ctrough] | Until 30 days after the last dosing | To evaluate the PK profile of MCLA-129 combined with Befotertinib in patients dvanced NSCLC with EGFR-sensitive mutations in Part 1. |
| Area under the concentration [AUC] | Until 30 days after the last dosing | To evaluate the PK profile of MCLA-129 combined with Befotertinib in patients dvanced NSCLC with EGFR-sensitive mutations in Part 1. |
| Maximum plasma concentration [Cmax] | Until 30 days after the last dosing | To evaluate the PK profile of MCLA-129 combined with Befotertinib in patients dvanced NSCLC with EGFR-sensitive mutations in Part 1. |
| Disease Control Rate (DCR) in Part 1 and 2 | From date of first treatment every 6 weeks until disease progression, death or withdrawal, whichever came first, approximately 2 years | To evaluate the efficacy of MCLA-129 combined with Befotertinib at RP2CD in patients of advanced NSCLC with EGFR-sensitive mutations in patients with advanced NSCLC and other solid tumors in Part 1 and 2 in terms of disease control rate (DCR). |
| Progression-Free Survival (PFS) in Part 1 and 2 | From date of first treatment every 6 weeks until disease progression, death or withdrawal, whichever came first, approximately 2 years | To evaluate the efficacy of MCLA-129 combined with Befotertinib at RP2CD in patients of advanced NSCLC with EGFR-sensitive mutations in patients with advanced NSCLC and other solid tumors in Part 1 and 2 in terms of Progression-free survival (PFS). |
| Duration of Response (DOR) in Part 1 and 2 | From date of first treatment every 6 weeks until disease progression, death or withdrawal, whichever came first, approximately 2 years | To evaluate the efficacy of MCLA-129 combined with Befotertinib at RP2CD in patients of advanced NSCLC with EGFR-sensitive mutations in patients with advanced NSCLC and other solid tumors in Part 1 and 2 in terms of duration of response (DOR). |
Countries
China
Contacts
Primary ContactDandan Zhang, Master
Outcome results
None listed