Ensartinib After Chemoradiotherapy in Stage III ALK-Mutated NSCLC

Shanghai Pulmonary Hospital, Shanghai, China

Status and phase

Not yet enrolling

Phase 2

Conditions

Ensartinib

ALK

Chemoradiotherapy

NSCLC Stage III

Treatments

Drug: Ensartinib 225mg

Drug: Placebo Ensartinib 225mg

Study type

Interventional

Funder types

Other

Identifiers

NCT07235306

L25-616

Details and patient eligibility

About

The PACIFIC study established the standard of care for immunotherapy consolidation after chemoradiotherapy (CRT) in patients with unresectable stage III non-small cell lung cancer (NSCLC). However, its benefit is limited in patients with driver gene mutations. The LAURA study established a new paradigm of targeted consolidation therapy after CRT for patients with EGFR mutations. Although retrospective data support the efficacy of ALK-TKIs, no randomized controlled trial (RCT) has clearly demonstrated the value of ALK-TKI maintenance therapy after CRT. This study adopts a multicenter, randomized, double-blind, placebo-controlled design aimed at evaluating the efficacy and safety of ensartinib in patients with ALK-positive unresectable stage III NSCLC.

Enrollment

45 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Male or female aged at least 18 years
Histologically or cytologically confirmed Stage III unresectable non-small cell lung cancer (NSCLC) with curative treatment intent
ALK mutations assessed by FISH, IHC, or NGS
ECOG Performance Status of 0 or 1
Completion of platinum-based concurrent or sequential chemoradiotherapy as per protocol requirements
Chemoradiotherapy must have been completed ≤ 6 weeks prior to randomization
No disease progression during or after chemoradiotherapy
Life expectancy > 12 weeks
Women of childbearing potential must have a negative urine pregnancy test within 7 days prior to initiation of treatment
Signed informed consent form obtained from the patient or their legally authorized representative
Male and female patients of childbearing potential agree to use highly effective contraception methods from before entering the trial, throughout the study, and until 8 weeks after discontinuation of study treatment

Exclusion criteria

Mixed histology of small cell and non-small cell lung cancer
Symptomatic pneumonitis following chemoradiotherapy that has not resolved to ≤ Grade 1 (per CTCAE criteria) prior to randomization;
Any unresolved toxicity from prior chemoradiotherapy with toxicity ≥ Grade 2 (according to CTCAE criteria);
Poor cardiac function, including but not limited to any of the following:
- Mean resting corrected QT interval (QTc) > 470 msec (obtained from 3 ECGs);
- Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG;
- Any factors that increase the risk of QTc prolongation or arrhythmic events, such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome, or concomitant use of any known drugs that prolong the QT interval and may lead to Torsades de Pointes;
Inadequate bone marrow reserve or organ function;
History of other malignant malignancies, except for adequately treated non-melanoma skin cancer or malignant lentigo, cured carcinoma in situ, or other solid tumors cured > 5 years ago with no evidence of disease and considered by the treating physician to have a low risk of recurrence;
Severe or uncontrolled systemic diseases: including uncontrolled hypertension and active bleeding tendency; or active infections, including hepatitis B, hepatitis C, and human immunodeficiency virus (HIV);
Refractory nausea and vomiting, chronic gastrointestinal disease, inability to swallow the formulated product, or previous significant bowel resection that would preclude adequate absorption of ensartinib;
Any prior chemotherapy, radiotherapy, immunotherapy, or investigational drug therapy beyond the definitive treatment for locally advanced disease;
Prior treatment with any ALK tyrosine kinase inhibitor (ALK-TKI);
Major surgery within 4 weeks prior to the first dose of study drug;
Current use of medications known to be strong inducers of CYP3A4 (which cannot be discontinued at least 3 weeks prior to the first dose of study drug);
Known hypersensitivity to ensartinib or any excipient in this product;
Pregnant or lactating women;
History of definite neurological or psychiatric disorders, including epilepsy or dementia;
Any other condition that, in the judgment of the investigator, would make the subject unsuitable for participation in the study.