Alflutinib Versus Alflutinib Plus Chemotherapy for NSCLC

Henan University of Science and Technology

Status and phase: Not yet enrolling; Phase 3; Phase 2

Conditions: NSCLC

Treatments: Drug: Alflutinib plus chemotherapy; Drug: Chemotherapy

Study type: Interventional

Funder types: Other

Identifiers

NCT05209256

ALF-IN-NSCLC-001

Details and patient eligibility

About

Aim: the aim of this study is to investigated whether the combination of alflutinib with cytotoxic chemotherapy might hold additive efficacy, as well as tolerability .

Full description

alflutinib is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that is active in the central nervous system (CNS) and which potently and selectively inhibits mutant forms of EGFR with both TKI-sensitising (activating) mutations and the T790M resistance-conferring mutation. However, resistance to alflutinib inevitably emerges. One promising strategy to further improve patient prognosis and to approach a cure is combination therapy with alflutinib and other agents such as cytotoxic chemotherapeutic drugs.

Enrollment: 90 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• histologically or cytologically diagnosed non-squamous NSCLC of stage IIIB or IV (based on the 7th edition of the TNM classification) or recurrent;
• an EGFR mutation, including an exon-19 deletion (Ex19del), L858R, or other (L861Q, G719A, G719C, or G719S), as well as the T790M mutation of EGFR as detected in a tissue or liquid biopsy sample obtained after disease progression during first-line EGFR-TKI (gefitinib, erlotinib, or afatinib) treatment;
• WHO performance status of 0 or 1;
• no prior neoadjuvant or adjuvant chemotherapy in the 12 months preceding study enrollment;
• adequate bone marrow reserve and organ function.

Exclusion criteria

• treatment with an EGFR-TKI within 7 days of the first dose of the study treatment;
• symptomatic CNS metastases;
• evidence of interstitial pneumonia, pulmonary fibrosis, or radiation pneumonitis requiring steroid treatment as revealed by a computed tomography (CT) scan.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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90 participants in 2 patient groups

Alflutinib plus chemotherapy

Experimental group

Description:

Those in the combination group received concurrent alflutinib (80 mg daily), as well as carboplatin (area under the curve \[AUC\] of 5 on day 1) and pemetrexed (500 mg/m2 on day 1) in a 3-week cycle for up to four cycles, followed by maintenance on alflutinib and pemetrexed until disease progression, unacceptable toxicity, or death.

Treatment:

Drug: Alflutinib plus chemotherapy

chemotherapy

Sham Comparator group

Description:

arboplatin (area under the curve \[AUC\] of 5 on day 1) and pemetrexed (500 mg/m2 on day 1) in a 3-week cycle for up to four cycles, followed by maintenance on alflutinib and pemetrexed until disease progression, unacceptable toxicity, or death.

Treatment:

Drug: Chemotherapy