Study of MCLA-129 Combined With Befotertinib in the Treatment of Advanced Non-small Cell Lung Cancer With EGFR Sensitive Mutation

NCT06015568 | Not Yet Recruiting Phase 1 DMC

• 1 other identifier: BTP-21712
• Study Type: interventional
• Target: 172
• Locations: 1 country
• Sites: 3

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.

Conditions

Non-Small Cell Lung Cancer、EGFR Sensitive Mutation

Outcome Measures

Primary Outcomes (4)

• Dose-Limiting Toxicity (DLT)

  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.

  First 28 days of treatment

• Maximum Tolerable Dose (MTD)

  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.

  First 28 days of treatment

• Treatment-Emergent Adverse Event (TEAE) in Part 1

  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).

  Until 30 days after the last dosing

• Overall Response Rate (ORR) in Part 2

  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)

  From date of first treatment every 6 weeks until disease progression, death or withdrawal, whichever came first, approximately 2 years

Secondary Outcomes (11)

• 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

• 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

• 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

• 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

• Anti-Drug Antibody (ADA) in Part 1 and 2

  Until 30 days after the last dosing

Study Arms (1)

MCLA-129+ Befotertinib

EXPERIMENTAL

Drug:MCLA-129 1500mg or 2000mg IV Q2W Other name:MCLA-129 Drug:Befotertinib (75 mg or 100 mg orally, once daily) Other name:D-0316

Drug: MCLA-129: 1500mg or 2000mg IV Q2W; Drug: Befotertinib: 75 mg or 100 mg Po QD

Interventions

MCLA-129: 1500mg or 2000mg IV Q2W DRUG

Every 28 days is a cycle until disease progression, death, initiation of new anti-tumor treatment, loss of follow-up, or voluntary withdrawal occurs

MCLA-129+ Befotertinib

Befotertinib: 75 mg or 100 mg Po QD DRUG

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.

MCLA-129+ Befotertinib

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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:
• With any of the following medical history within 6 months before first administration of the investigational drug: myocardial infarction, unstable angina, stroke, transient ischemic attack, coronary or peripheral artery bypass, or any acute coronary syndrome.
• With abnormal ECG corrected QT interval (QTcF) at rest in the screening period. Remeasurement is made twice at intervals of more than 5 minutes. For average QTcF of 3 times ECG inspections: male: ≥ 450 msec, and female: ≥ 470 msec. With clinically significant abnormal heart rate, conduction, and ECG form at rest, e.g. complete left bundle branch block, third-degree conduction block, second-degree conduction block, and PR interval \> 250 msec, double law, triple law, preexcitation syndrome, etc.
• Poorly controlled hypertension in the investigator's opinion (systolic blood pressure \> 180 mmHg, or diastolic blood pressure \> 100 mmHg).
• New York Heart Association Grade III-IV congestive heart failure, or hospitalization due to congestive heart failure within 6 months before first administration of the investigational drug.
• Pericarditis/clinically significant pericardial effusion.
• Cardiomyopathy.
• ther clinically significant cardiovascular disordesr as believed by investigators.

Sponsors & Collaborators

• Betta Pharmaceuticals Co., Ltd.: lead

Study Sites (3)

The first affiliated hospital of bengbu medical college

Bengbu, Anhui, China

Location

Hunan cancer hospital

Changsha, Hunan, China

Location

Shanghai chest hospital

Shanghai, China

Location

Study Officials

• Shun Lu, M.D.

  Shanghai Chest Hospital

  STUDY CHAIR

Central Study Contacts

Dandan Zhang, Master

CONTACT

+86 18626898205; dandan.zhang@bettapharma.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 21, 2023
• First Posted: August 29, 2023
• Study Start: September 1, 2023
• Primary Completion (Estimated): November 4, 2028
• Study Completion (Estimated): July 4, 2029
• Last Updated: August 29, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (3)