Non-Small Cell Lung Cancer
Conditions
Brief summary
This is a multi-center, open-label, phase II clinical study of MCLA-129 as monotherapy in patients with advanced non-small cell lung cancer (NSCLC) with actionable gene alterations and MET amplification to evaluate the efficacy, safety, pharmacokinetic characteristics of MCLA-129.
Detailed description
This is a multi-center, open-label, monotherapy, multi-cohort phase II study of MCLA-129 in patients with advanced non-small cell lung cancer (NSCLC) with actionable gene alterations and MET amplification, designed to evaluate the efficacy, safety, and PK profiles of MCLA-129 in the target population. Subjects who must experience disease progression or intolerance after standard treatment eligible through screening will be divided into the following 4 cohorts: Cohort 1 and Cohort 2: Patients with advanced NSCLC with previously detected EGFR-sensitive mutations (exon 19 deletion or exon 21 L858R mutation) who have progressed after prior standard treatment which includes 1) first-generation or second-generation EGFR-TKIs, with T790M mutation requiring third-generation EGFR-TKIs and platinum-based chemotherapy; or 2) first-generation or second-generation EGFR-TKIs, with T790M mutation negative or unknown status. Subjects in Cohort 1: Patients with MET amplification after failure of treatment with EGFR-TKIs. Subjects in Cohort 2: Patients who experienced disease progression or intolerance after MET inhibitors and benefited from such treatment. Cohort 3 and Cohort 4: Patients with advanced NSCLC with previously detected actionable gene alterations who had progressed after treatment with corresponding inhibitors and platinum-based chemotherapy. Subjects in Cohort 3: Patients with MET amplification, after failure of treatment with the corresponding driver gene inhibitors. Subjects in Cohort 4 should also meet: Patients who experienced disease progression or intolerance after MET inhibitors and benefited from such treatment.
Interventions
DRUGMCLA-129
MCLA-129 will be administered by intravenous infusion on the 28-day treatment cycle.
Sponsors
Betta Pharmaceuticals Co., Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects are ≥ 18 years of age, regardless of gender. * Subjects must have histologically or cytologically confirmed locally advanced unresectable or metastatic NSCLC. * Subjects who must experience disease progression or intolerance after standard treatment eligible through screening will be divided into the following 4 cohorts: Cohort 1 and Cohort 2: Patients with advanced NSCLC with previously detected EGFR-sensitive mutations (exon 19 deletion or exon 21 L858R mutation) who have progressed after prior standard treatment which includes 1) first-generation or second-generation EGFR-TKIs, with T790M mutation requiring third-generation EGFR-TKIs and platinum-based chemotherapy; or 2) first-generation or second-generation EGFR-TKIs, with T790M mutation negative or unknown status. Subjects in Cohort 1: Patients with MET amplification after failure of treatment with EGFR-TKIs. Subjects in Cohort 2: Patients who experienced disease progression or intolerance after MET inhibitors and benefited from such treatment. Cohort 3 and Cohort 4: Patients with advanced NSCLC with previously detected actionable gene alterations who had progressed after treatment with corresponding inhibitors and platinum-based chemotherapy. Subjects in Cohort 3: Patients with MET amplification after failure of treatment with the corresponding driver gene inhibitors. Subjects in Cohort 4: Patients who experienced disease progression or intolerance after MET inhibitors and benefited from such treatment. * Subjects must have measurable lesions that meet the definition of RECIST v1.1. Selected target lesions must meet one of the following two criteria: 1) no prior local therapy or radiation or 2) subsequent progression occurs within the prior local therapy area as determined by RECIST v1.1.. * Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. * Expected survival ≥3 months. * Have certain functions of organ systems (no blood transfusion or use of blood component or G-CSF support within 14 days before testing), defined as follows: * Absolute neutrophil count (ANC) ≥1.5×10\^9 /L. * Platelet count (PLT）≥75×10\^9 /L. * Hemoglobin (HGB) ≥100 g/L. * Serum albumin ≥ 30 g/L. * Total bilirubin ≤1.5 times the upper limit of normal (ULN). * Alanine amino transferase (ALT) and aspartate amino transferase (AST) ≤3×ULN. * Creatinine ≤1.5×ULN. If creatinine is \>1.5×ULN, creatinine clearance ≥50 mL/min as calculated by Cockcroft-Gault formula, or 24-hour urine creatinine clearance ≥50 mL/min is measured, the patients can still be enrolled. * Willing and able to follow the trial and follow-up procedures. * Able to understand the nature of the trial and voluntarily sign the written informed consent form.
Exclusion criteria
* Have received an investigational product or antitumor drug treatment (including known anti-tumor traditional Chinese medicine treatment) within 14 days before the first dose of MCLA-129 or within 5 half-lives of the drug (whichever is longer) (for a drug with a long half-life, it is required that the interval from the last dose to be at most 4 weeks; for chemotherapy with delayed toxicity, such as nitrosourea or mitomycin C, it shall be 6 weeks before \[the treatment\]). * Have undergone a major surgery and radiotherapy (local palliative radiotherapy is allowed 2 weeks or more prior to the first dose) within 4 weeks prior to the first dose of MCLA-129. * Have previously received systemic anti-tumor therapy beyond the fourth line (excluding maintenance therapy). * Prior use of EGFR/c-Met bispecific antibody or ADC drugs (Amivantamab \[JNJ-61186372\], EMB-01, GB263T, PM1080/HS-20117, TAVO412, YH013/DM005, AZD9592, or SHR-9839). * Prior to the first dose of MCLA-129, previous treatment-related toxicities have not resolved to Grade 1 or below (CTCAE 5.0 criteria), except for alopecia. * Prior to the first dose of MCLA-129, previous treatment-related toxicities have not resolved to Grade 1 or below (CTCAE 5.0 criteria), except for alopecia. * Have had other malignancies within the past 3 years, except for cancers that have been totally cured or locally cured, such as basal or squamous cell carcinoma of the skin, cervical cancer in situ, or breast cancer in situ. * Patients with primary malignant tumor of central nervous system, or metastases to meninges, or concomitantly with symptomatic brain metastases, or new therapy naive brain metastases. Note: Patients with brain metastases who have received treatment for brain metastases (including systemic and local therapies against brain metastases) with no obvious symptoms and stable condition, and do not require drug therapy such as steroids and/or dehydration to reduce intracranial pressure within 2 weeks before enrollment and have no risk of brain bleeding can be enrolled. * With clinically significant cardiovascular and cerebrovascular diseases. * 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 |
|---|---|---|
| Overall Response Rate (ORR) | 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 at RP2D in patients with advanced NSCLC and other solid tumors in each cohort in Part 2 in terms of overall response rate (ORR) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease Control Rate (DCR) | 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 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) | 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 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) | 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 in patients with advanced NSCLC and other solid tumors in Part 1 and 2 in terms of duration of response (DOR). |
| Time to response (TTR) | 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 in patients with advanced NSCLC and other solid tumors in Part 1 and 2 in terms of time to response (TTR). |
| Clinical benefit rate (CBR) | 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 in patients with advanced NSCLC and other solid tumors in Part 1 and 2 in terms of clinical benefit rate (CBR). |
| Treatment-Emergent Adverse Event (TEAE) | Until 30 days after the last dosing | To evaluate the safety of MCLA-129 in patients with advanced NSCLC and other solid tumors in Part 1 and 2 in terms of treatment-emergent adverse event (TEAE). |
| Area under the concentration versus time curve [AUC0-∞] | : Until 30 days after the last dosing. | To evaluate the population PK profile of MCLA-129 in patients with advanced NSCLC and other solid tumors in Part 1 and 2 in terms of area under the concentration versus time curve \[AUC0-∞\]. |
| Anti-Drug Antibody (ADA) | 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) | 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 in patients with advanced NSCLC and other solid tumors in Part 1 and 2 in terms of overall survival (OS). |
Countries
China
Contacts
Primary ContactWanlin Chen, Master
Outcome results
None listed