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Optimizing local ablative therapy with brigatinib for advanced ALK-positive lung cancer

Optimization of Treatment With Brigatinib in Patients With Advanced NSCLC Harboring an ALK Rearrangement by LAT at the Time of Best Response: A Multicenter Open Phase Two Trial (OPTALK)

Phase 2 Interventional Groupe Francais De Pneumo-Cancerologie · NCT06620835

This study will test whether adding targeted local treatments to ongoing brigatinib helps people with advanced ALK-positive non-small cell lung cancer who have a limited number of remaining tumors.

Quick facts

PhasePhase 2
Study typeInterventional
Enrollment45 (estimated)
Ages18 Years and up
SexAll
SponsorGroupe Francais De Pneumo-Cancerologie Academic / other
Drugs / interventionsbrigatinib, radiation
Locations27 sites (Brest and 26 other locations)
Trial IDNCT06620835 on ClinicalTrials.gov

What this trial studies

Approximately 45 adults in France with advanced ALK-rearranged NSCLC who have been on first-line brigatinib for 3–9 months and show response or stable disease will be enrolled. Eligible participants must have oligometastatic disease (five lesions or fewer, maximum two per organ) and at least one residual lesion accessible to local ablation. Selected patients will receive local ablative options such as surgery, stereotactic radiosurgery (SRS), or stereotactic body radiotherapy (SBRT) while continuing brigatinib, with imaging assessments by RECIST 1.1 and blood testing. The trial seeks to define the optimal timing and feasibility of adding LAT to ongoing brigatinib in this population.

Who should consider this trial

Good fit: Adults with advanced ALK-rearranged NSCLC who are TKI-naïve, have been on first-line brigatinib for 3–9 months with response or stable disease, and have oligometastatic disease with at least one lesion suitable for local ablation.

Not a fit: Patients with widespread metastatic disease (more than five lesions), a complete response with no residual lesions, prior ALK TKI exposure, or medical contraindications to local ablation are unlikely to benefit from this approach.

Why it matters

Potential benefit: If successful, this approach could extend the period of disease control and delay the need to change systemic therapy for patients with limited progression.

How similar studies have performed: Combining local ablative therapy with targeted TKIs has shown encouraging results in small series and retrospective studies for oligoprogressive disease, but randomized evidence specifically optimizing timing with brigatinib in first-line ALK-positive NSCLC is limited.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

* Age 18 years or older at diagnosis.
* Stage 3 non eligible for chemoradiotherapy or stage 4 NSCLC, histologically or cytologically confirmed NSCLC.
* Tyrosine Kinase Inhibitor (TKI) treatment naïve.
* ALK rearrangements identified by a validated technique (either Immunohistochimy (IHC), fluorescence in situ hybridization (FISH) or Ribonucleic Acid (RNA)seq, in tissue or liquid biopsy)
* Stable disease or response after initiation brigatinib treatment (at least 3 to 9 months) according to RECIST 1.1
* At least one site of residual site for LAT (ie. participant should not have a complete response)
* Oligometastatic disease (five metastatic lesions or less and a maximum of two lesions per organ) de novo or induced
* Eligible for local ablative treatment possible (either alone or combined): surgery, minimally invasive form of surgical radiosurgery (Stereotactic Radio Surgery (SRS)) (18 to 20 Gy in single fraction) or radiotherapy (SBRT) (27 to 54 Gy in 3 fractions or 45 to 50 Gy in 5 fractions), radiofrequency or cryotherapy (=thermoablation)
* An Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤2.
* Life expectancy above 12 weeks as assessed by treating investigator.
* Brain metastases at inclusion are allowed if asymptomatic
* No history of other malignant tumor during the previous 5 years, except for adequately treated carcinomas (in situ cervical carcinoma, basal cell carcinoma, squamous cell skin carcinoma) and low-grade localized prostate cancer (Gleason \<6).
* Adequate organ function, as demonstrated by laboratory results prior to the first administration of study treatment: normal hepatic function (bilirubin ≤1.5 x upper limit of normal (ULN), alanine aminotransferase (ALA T) and aspartate aminotransferase (ASAT) ≤2.5 x ULN or ≤5 x ULN in case of liver metastases), renal function (calculated creatinine clearance (CrCl, using local formula) above 45 ml/mn), normal hematological function (absolute neutrophil count

  ≥1.5 x 109/L and/or platelets ≥100 x 109/L, hemoglobin ≥8 g/dL), normal coagulation function (International Normalized Ratio (INR) or prothrombin time ≤1.5 x ULN and activated partial thromboplastin time (aPTT) or partial thromboplastin time (PTT) ≤1.5 x ULN unless the patient is receiving anticoagulant therapy)
* For patients of childbearing potential: Women of childbearing potential should use effective non-hormonal contraception during treatment with brigatinib and for at least 4 months following the final dose. Men with female partners of childbearing potential should use effective contraception during treatment and for at least 3 months after the last dose of brigatinib.
* Signed informed consent to participate in the study
* Affiliation with or benefit from French social security

Exclusion Criteria:

* NSCLC without known ALK rearrangements
* Neuroendocrine tumor (even in case of mixed tumors).
* Uncontrolled and untreated superior cava syndrome.
* Unstable symptomatic brain metastases despite corticosteroid
* Leptomeningeal, pericardial, pleural and mesenteric lesions, lymphangitic spread (any tumoral lesions not amenable to definitive local therapy). Peri tumoral lymphangitic spread around a tumor, but limited to a lobe, may be treated by surgery).
* Serious concurrent conditions during the previous 6 months (severe or unstable angina pectoris, coronary or peripheral artery bypass graft of \<6 months, class 3 or 4 congestive heart failure, ischemic stroke, grade ≥2 peripheral neuropathy, psychiatric or neurological disorders that may interfere with the patient's understanding of the study or with his/her informed consent.
* Severe or non-controlled systemic diseases deemed incompatible with the protocol.
* Severe infections within 4 weeks prior to inclusion, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia.
* Psychological, family, social, or geographical factors that may interfere with the monitoring of the patient as defined by the protocol.
* Any protected person (legal person protected by legal protection \[guardianship, tutorship\], person deprived of liberty, pregnant woman, breastfeeding woman, and minor).
* Patients who participated in other concomitant studies unless observational and received study therapy or used an investigational device within 4 weeks prior to start of study treatment
* Known allergies or adverse reactions to the study drugs
* Lung function not compatible with surgery or radiation

Where this trial is running

Brest and 26 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions NSCLCLung cancerALK rearrangementgene mutation
Last reviewed 2026-06-09 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.