About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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).

Cohort A: Previously diagnosed EGFR-sensitive mutations and no systemic antitumor therapy for locally advanced or metastatic NSCLC.

Disqualifiers

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.

Trial design

Design model

Single group

Treatments tested in this trial

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
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.

Treatment groups

172 Participants

are divided into 1 treatment group

Group A: MCLA-129+ BefotertinibExperimental treatment 2 interventions

Trial outcomes

Primary outcomes

1

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.

Time frame

First 28 days of treatment

2

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.

Time frame

First 28 days of treatment

3

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).

Time frame

Until 30 days after the last dosing

4

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)

Time frame