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 Updated 12/27/2022
The Americas, Europe, China,
Other Asia/Africa, Australia
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DateTrial Summary PhaseInclusion CriteriaLocationsSponsorsIdentifier- LINKComments
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Studies Recruiting for Surgically Resectable Disease - ALK NSCLC Stage 1A to IIIA
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5/20/2021Alectinib before surgery (Neo-adjuvant) in stage III
ALK Positive NSCLC (ALNEO)

IILocally advanced stage 3 ALK+ adenocarcinoma of the lung
Mixed histology okay if adenocarcinoma is prominent
Candidate for surgical resection
No prior systemic treatment for lung cancer
Italy: Aviano, Bari, Bologna, Catania, Firenze, Genova,Lido De Camaiore. Meldola, Modela, Monza, Napoli, Obassano, Padova, Parma, Perugia, Roma, Rozzano. Verona.
Gruppo Oncologico Italiano di Ricerca ClinicaNCT05015010 


Alectinib will be adminstered 8 weeks
before surgery.
After surgery, alectinib will continue up to
96 weeks.
5
7/31/2020Alectinib, (Entrectinib, or Vemurafenib Plus Cobimetinib) in Resectable Stages I-III NSCLC with ALK,(ROS-1, NTRK or BRAFv600E) Molecular Alterations (NAUTIKA-1)
(Stages IA2 - IIIAB)
IIResectable stage 1A2, 1B, 2, 3A or selected 3B ALK+ NSCLC
Will receive up to 8 weeks Alectinib before surgical resection
and/or radiotherapy as recommended by treating physician		USA: LA, Orange, Sacramento, CA; Tampa FL, Boston MA, Ann Arbor, MI: Columbia, St Louis, MO; Lebanon NH, NY, NY; Cleveland, Columbus OH, Houston TX, Washington DC, Fairfax, VA, Seattle WA.
Genentech
NCT04302025


Innovative in that tumors will be
reduced with Alectinib before
resection. May also be possible to
continue Alectinib after surgery/radiation.
6
8/18/2014



Crizotininb in patients with IB-IIIA ALK NSCLC that has
been removed by surgery
(An ALCHEMIST Treatment Trial)

III


Stage IB, II, or non-squamous IIIA , ALK NSCLC - NED
Complete resection of tumors with negative margins
No prior treatment with ALK TKI
Surgery 4 weeks to 300 days prior (depends on situation)
Adjuvant radiation or chemo okay		USA: 1498 sites



ECOG-ACRIN Reserach
National Cancer Institute


NCT02201992

Randomized to Crizotinib
up to 2 years vs
observation without Criz

7
Studies Recruiting for Stage III Unresectable Disease - ALK NSCLC
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7/15/2022
Alectinib vs durvalumab: A Study Evaluating the Efficacy and Safety of Multiple Therapies in Cohorts of Participants With Locally Advanced, Unresectable, Stage III Non-Small Cell Lung Cancer (NSCLC)



III






Newly diagnosed, Stage III unresectable ALK+ NSCLC,
Prior receipt of at least 2 cycles of platinum-based chemotherapy
Prior radiation okay
(ROS1 or RET mutations included with their assocated TKIs)







USA, Australia, Canada, China, Costa Rica, Hong Kong, Japan, Korea, Thailand.
Hoffmann-La RocheNCT05170204




Particiapants will be randomized to receive either alectninb or durvalumab after chemotherapy.Durvalumab is an checkpoint inhibitor immunotherapy, and this class of drug is usually not effective in later stages of ALK lung cancer. Based on current research, alectninib is likely to be far more effective than durvalumab. Anyone entering this trial should have an excellent understanding of risks and benefits, preferably beyond what they are told by their oncologist.
9
Recruiting for 1st Line ALK Inhibitor Stage IIIB to IV (No Prior ALK TKI Treatment)
10
10/15/2022

Immunotherapy or Targeted Therapy With or Without Stereotactic Radiosurgery for Patients With Brain Metastases From Melanoma or Non-small Cell Lung Cancer (USZ-STRIKE)
III

Newly diagnosed ALK NSCLC with brain metastases
Mild symptoms from brain met(s), requiring no more than 4 mg dexamethasone.
Prior surgery for brain mets allowed
No previous radiation for brain mets		Germany: Zurich.
Other sites planned in: Italy, Amsterdam, Switzerland, UK
ETOP IBCSG Partners Foundation
USZ Foundation		NCT05522660 

Participants will be randomized to receive ALK inhibitor alone vs. SRS brain radiation before ALK inhibitor.
11
5/18/2022

Study of Safety and Efficacy of Brigatinib Plus Chemotherapy or Brigatinib Only in Advanced ALK-Positive Lung Cancer (MASTERPROTOCOL ALK)


II




Advanced ALK+ NSCLC, not eligible for local treatment
TKI naïve
Brain mets must be stable
At least 12 months since chomtherapy for earlier stage lung cancer





France: Boulogne
Many other sites in France planned
Intergroupe Francophone de Cancerologie ThoraciqueNCT05200481


Participants with no previous TKI use will be randomized to receive either brigatinib plus 4 cycles of carbo/pemetrexed chemotherapy or brigatinib alone.
12
3/23/2022



Comparison of Standard Dose Alectinib to Alectinib in Adjusted Dose Based on Alectinib Bloodlevels (ADAPT ALEC)




IV







Advanced or recurrent or metastatic ALK+ NSCLC
TKI naïve
One previous line of chemotherapy okay
Brain mets or LMD okay if stable






Netherlands: Rotterdam, Groningnen, Maastricht
5 more sites in Netherlands planned. 		Various University and Cancer Center sponsors in NetherlandsNCT05525338

Randomized to standard dose alectnib vs dose adjustments based on blood levels of the drug.
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03/30/2020

Advancing Brigatinib Properties in ALK+ NSCLC Patients by Deep Phenotyping - Brigatinib first line in Germany



II



Inorperable stage III or stage IV ALK+ NSCLC
Willing to have NGS biopsy if not done already
No prior TKIs. 1-2 cycles chemotherapy or brain radiation okay
Brain mets must be stable

Germany: Berlin, Essen, Esslingen, Frankfurt, Freiburg, Georgsmarienhutte, Gieben, Hamburg, Hamm, Hannover, Heidelberg, Jena, Koln, Mainz, Munchen, Munster, Oldenburg, Regensburg, Stuttgart, Warzburg, Ulm

Institut fur KlinischeKrebforschung IKF GmbHNCT04318938

Randomized potential crossover study comparing first line Brigatinib with first line investigator's choice 2nd gen TKI
14
10/1/2019
OMEGA, A Randomized Trial of Local Ablative Therapy Vs. Conventional Treatment in Oligometastatic NSCLC


III




Advanced or metastatic ALK+ NSCLC
No previous systemic treatment (may consider if started systemic treatment 3 months before without progression)
Primary tumor amenable to surgery or radiation
Between 1-3 metastatic lesions




Italy: Verona
Azienda Ospedaliera Universitaria IntegrataNCT03827577

Randomized to ALK TKI vs Local Ablative Therapy (radation or surgery) to all metastatic sites, with ALK TKI
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Recruiting for 1st or 2nd+ Line Treatment (ALK TKI Treatment Naïve or Prior ALK TKIs)
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6/17/2022Real-Time Monitoring of Symptoms in Lung Cancer Patients Receiving Oral Targeted Therapies (Lung001)

NA
ALKlung cancer (or EGFR)
Currently prescribed TKI; either < 4 weeks or > 4 weeks
Able to download a smart device app and use Fitbit; WiFi
English-speaking
USA: Charlottesville VA


University of Virginia
NCT05370469

Choice and dose of TKI will be determined by the treating oncologist. Symptoms and adverse events will be monitored by app and Fitbit. Outsomes are to test feasability of approach and estimate frequency of side effects.
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4/1/2022Exercise in Extended Oncogene Addicted Lung Cancer
In Active Treatment (EXcellenT)		N/A


ALK NSCLC on first or second line systemic treatment (TKI)
Not suitable for local treatment
Prior radiotherapy and chemotherapy allowed

Italy: AUSL Romagna Rimini
AUSL Romagna Rimini
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano		NCT05306652


Patients will be randomized to receive supervised physical activity vs. unsupervised physical acitivity. Qualiy of life and overall survival will be measured between the two groups.
***
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12/10/2021Personalized Dendritic Cell Vaccines in NSCLC
(ALK included)

I
Advanced ALK NSCLC stage IV or unresectable stage III
On standard of care treatment with crizotinib, alectinib,or lorlatinib
No progression on current treatment
Switzerland: Lausanne


Centre Hospitalier Universitaire Vaudois
NCT05195619 

Six doses of personalized dendritic cell vaccine will be added to standard of care ALK inhibitor treatment
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8/1/2021Local consolidative treatment versus conventional care after first line systemic anti-cancer treatment: RAdical Management Of Advanced Non-small cell lung cancer (RAMON)I/II
ALK lung cancer (and other lung cancers) who have been on ALK inhibitors and have evidence of residual disease.
UK: 40 sites. 244 patients total
NHR, Gy and St Thomas NHS, Foundation Trust
https://fundingawards.nihr.ac.uk/award/NIHR131306Patients will be randomized to receive standard care (no LCT) vs local consolidative treatment to all sites of residual disease. LCT may consist of radiation, surgery, or ablation.
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3/18/2021
Ensartinib in Combination with Platinum-Based Chemotherapy and Bevacizumab in ALK+ NSCLC


I

Stage 4 or stage 3C NSCLC with ALK rearrangement
Treatment naïve or after progression on any number of TKIs
Asymtomatic brain mets okay
Prior platinum chemo okay in certain circumstances
No LMD


USA: Houston, TX (MD Anderson)



MD Anderson Cancer CenterNCT04837716  


Patients receive ensartinib, carbo/pemetrexed, and bevacizumab(Avastin) all at the same time for 4 (21 day) cycles. Then maintenance with ensartinib and bevacizumab is continued indefinitely.
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11/10/2020
Observation or Upfront Cranial Radiation in Oncogene Driver Mutated NSCLC With Asymptomatic Brain Metastases (including ALK)
III


ALK or EGFR lung cancer
Asymptomatic brain metastases
No previous brain radiation
No brain stem metastases

India: Mumbai, Tata Memorial Hospital



Tata Memorial Hospital
NCT05236946  

Patients with brain metastases will be randomized to receive brain radiation (SRS or WBR) before ALK-TKI, or ALK-TKI alone
22
11/11/2019


TKI Alone Versus TKI and Local Consolidative Radiation Therapy in ALK (or other oncogene) NSCLC
(TARGET-01)

II

Oncogene driver NSCLC
At least 2-4 months of TKI treatment without progression
1-5 sites of metastatic disease not including primary tumor and regional nodes
No prior radiation to thorax		India: Mumbai, Tata Memoral Hospital

Tata Memorial Hospital
NCT05277844 

Participants will be randomized to receive
radiation local consolidative therpy with TKI
vs. TKI alone
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9/14/2017


Alectinib combined with Cobimetinib (MEK inhibitor)
in advanced ALK NSCLC

IB/II


ALK stage IV
Treatment naïve or previously treated with ALK TKIs or chemo
Brain mets must be treated if progresssed on Alectinib		USA: Boston - Mass General



Mass General
Genentech
NCT03202940  


24
10/7/2016

Lorlatinib with brain mets and/or LMD in the absence of
measurable lesions outside the brain
II

Treatment naïve or previous ALK TKIs or chemo
LMD or at least one brain met 5 mm or larger
No measurable disease outside brain or nervous system		USA: Boston - Mass General


Mass General
NCT02927340

25
10/1/2015

Alectinib combined with Bevacizumab (anitangiogenesis)
In advanced ALK NSCLC
I/II

ALK stage IIIB or IV. Prior ALK-TKIs okay
Prior chemo okay
Brain mets must be irradiated or surgically removed before starting study
Mexico: Mexico City

Instituto Nacional De Cancerologia de Mexico
Roche Pharma AG
NCT03779191

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Recruiting for ALK NSCLC 2nd-3rd-4th Line Treatment After One or More ALK TKIs
27
7/2022

A Study of LP-300 With Carboplatin and Pemetrexed in Never Smokers With Advanced Lung Adenocarcinoma (HARMONIC)II


Inoperable advanced (stage III or IV) ALK adenocarcinoma
Other targetable mutations included
Never smoker
Has exhausted TKIs
Brain mets must be stable
Prior radiation okay
USA: Rolling Meadows IL, Canton OHLantern PharmaNCT05456256

Never smokers with lung cancer will be given LP-300 with chemotherapy after exhauting TKIs.A subset of never smokers in another trial had improved survival with this combination.
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5/1/2022A Study of NVL-655 (new ALK TKI targeting ALK and resistance mutations) in Patients With Advanced NSCLC and Other Solid Tumors Harboring ALK Rearrangement or Activating ALK Mutation (ALKOVE-1)I/II



Advanced or metastatic ALK lung cancer or solid tumor
For NSCLC: progression after 1-3 lines of TKI treatment, including crizotinib, ceritinib, alectinib, brigatinib, or lorlatinib.
For ALK soild tumors: at least one prior systemic anticancer therapy, or no satifactory standard therapy exists
Measurable disease according to RECIST 1.1


USA: Orange CA, Denver CO, Boston MA, Detroit MI, Nashville TN, NYNY, Seattle WA.
France: Toulouse Cedex, Villejuif (Gustave Roussy)
Spain: Barcelona
Nuvalent		NCT05384626 


NVL-655 is a new ALK inhibitor that targets resistance mutations, including compound mutations that can occur after lorlatinib treatment.
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7/8/2021SNK01 (Super Natural Killer Cells) in combination with gemcitabine chemotherapy and/or EGFR antibody in NSCLC who were failed by TKI treatment (SNK_ASTER)

I/II
Advanced NSCLC with at least one gene mutation (incl. ALK)
Progression after at least one TKI
Previous platinum chemotherapy okay
Stable brain mets okay
Must stop TKI 2 weeks before enrollment		Korea: SeoulNKMAX Co, ltd
NCT04872634

EGFR inhibitor is the monoclonal antibody cetuximab. It will be added to nautral killer cells and gemcitabine chemo in some patients.
EGFR mutation does not determine who gets the EGFR antibody.
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3/17/2021ARRY558/PF-07284892 (SHP2 inhibitor) as a Single Agent and in Combination (with lorlatinib) in Participants with Advanced Solid Tumors - Including ALK NSCLC
I
Advanced ALK+ NSCLC (and other solid tumors)
Prior lorlatinib okay
Prior chemo okay
Okay if no prior loratinib
No brain mets larger than 4 cm		USA: Orange CA, Grand Rapids MI, NYNY, Franklin, Nashville TN, Houston TX,
Pfizer

NCT04800822  

This drug inhibits the SHP2/PTPN-11 cell proliferation signalling pathway
31
11/17/2020
Lorlatinib Activity Based on ALK Resistance Mutations Detected on Blood (ALKALINE)

II


Previous treatment with at least one 2nd generation ALK inhibitor. Progression on last ALK inhibitor
At least one tumor outside of brain

Belgium: Brussels, Edegam, Yvoir. France: Avignon, Bobigny, Brest, Creteil, Villejuif. Jordan: Amman, Netherlands: Amsterdam, Maastricht, Rotterdam, Norway: Oslo, Spain: Barcelona, Madrid, Palma de Mallorca, Pamplona, Sevilla. UK: Manchester



EORTC
NCT04127110

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10/8/2020Lorlatinib with ALK-Positive NSCLC
(which has progressed on first-line certinib or alectinib)


IV
Stage 4 ALK+ NSCLC
Disease progression after certinib or alectinib as first TKI
Prior chemo okay if before TKI
Asymptomatic brain mets and LMD okay
USA: Orange CA, Italy: Monza, Avellino, Aviano, Parma, Milano, Roma.. Poland: Lublin, Szczecin, Spain: Barcelona, Madrid, Malaga.A Coruna, Sevilla: Switzerland Graubuenden; UK: London, Manchester
Pfizer

NCT04362072

This study will assess overall and intracranial response rate or single agent lorlatinib after progression on first line ceritinib or alectinib

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8/1/2020Lorlatinib (PF-06463922) Monotherapy After Failure of First-line Second-generation ALK Kinase Inhibitor in Patients With Advanced ALK-positive Non-small Cell Lung Cancer
(ORAKLE)
II
Advanced or metastatic ALK+ NSCLC
Progression on first line Alectinib or Brigatinib
No previous chemotherapy
Tissue biopsy of progressed tumor is mandatory		France: Angers, Annecy, Bayonne, Besancon, Bordeaux, Boulogne, Caen, Colmar, Creteil, Dijon, Grenoble, LeMans, Lille, Lyon, Marseille, Montpeloier, Mulhouse, Nantes, Orleans, Paris, Pierre-Benite, Saint Quentin, Strasbourg, Suresnes, Toulon, Toulouse, VandoeuvreIntergroupe Frondophone de Cancerlogie
Thoracique

NCT04111705

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5/15/2020Brigatinib in ALK-positive NSCLC Identified Via Blood Assays (KOREA)

II
Disease progression with one ALK-TKI treatment for inoperable stage 3 or metastatic ALK+ NSCLC
ALK rearrangement per blood biopsy
Stable brain mets okay
Korea: GoyangJi-youn Han
Seoul National Univ. Hosp
Severance Hospital
Seoul Nat. Univ. Bundang
NCT04074993

 
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5/1/2020Lorlatinib Combinations in ALK Lung Cancer
(Lorlatinib + Crizotinib / Lorlatinib + Binimetinib / Lorlatinib + TNO155 )

I/II
Advanced ALK+ NSCLC
Prior Chemo okay
Progression on at least one ALK TKI
Brain mets must be stable. LMD is included in trial.		USA: Boston: Massachsetts General,
Beth Israel Deaconess Medical Center		Mass General
Array Biopharma
Pfizer
NCT04292119

Assigned to either Lor/Criz or
Lor/Binimetinib or Lor/TNO155

Unless biopsy shows MET, then receive Lor/Criz
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1/13/2020Brigatinib and Bevacizumab (angiogenesis inhibitor) for the Treatment of ALK-Rearranged Locally Advanced, Metastatic, or Recurrent Non-small Cell Lung Cancer
I
Advanced or metastatic ALK+ NSCLC
Progression on at least one ALK inhibitor
Prior chemotherapy okay
Asymptomatic brain mets okay
Willing to have NGS biopsy at entry and progression		USA: Duarte CA; Denver CO. Sites p lanned in Chicago IL and Madison WI. Northwestern University
National Cancer Institute

NCT04227028 

Combo Brigatinib and Avastin after progression on at least one TKI
37
9/26/2019
Platinum-Pemetrexed-Atezolizumab (+/- Bevacizumab) for Patients With Stage IIIB/IV Non-squamous Non-small Cell Lung Cancer With ...ALK Rearrangement ...Progressing After Targeted Therapies (GFPC 06-2018)

II
Advanced or metastatic ALK+ NSCLC
Progression on at least one ALK inhibitor
No more than 2 prior cycles of chemotherapy
No untreated active brain mets		France: Angers, Annecy, Brest, Caen, Creteil, Grenoble, La Reunion, Limoges, Lyon, Marseilles, Orleans, Paris, Pessac, Pierre-Benite, Rennes, Rouen, Strasbourg, Toloun, Toulouse, Villenave-d"Ornon. More sites planned in France


Centre Francois Baclesse


NCT0402558

Non-random addition of Bevacizumab to Carbo/Alimta/Tecentriq.
Tecentriq is a checkpoint inhibitor immunotherapy. This class of drug is seldom effective in ALK.

38
8/27/2019Atezolizumab + Carbo/Paclitaxel/Bevacizumab in ALK or EGFR NSCLC

III
Advanced or metastatic ALK+ NSCLC
Progression on at least one ALK TKI
No previous chemotherapy for stage 4
Brain mets must be stable. 		Korea: SeoulSamsung Medical Center


NCT03991403

This is a randomized study comparing IMPower 150 combo of Tecentriq/Carbo/Paclitaxel/Avastin to Carbo/Alimta Doublet
39
6/13/2019
Alternating Lorlatinib with Crizotinib in ALK NSCLC progressed on a 2nd generation ALK Inhibitor
(Lorlatinib x 8 weeks, then Crizotinib x 4 weeks
repeated indefinitely) ALKTERNATE		I/II
Stage IV ALK+ NSCLC per FISH or IHC
Confirmed progression on Ceritinib, Alectinib, or Brigatinib
Past chemotherapy or radiation okay
Brain mets okay if stable for at least 14 days
No prior Lorlatinib treatment		Australia: Melbourne, St. Leonards (Sydney)Pfizer
Fight for a Cure
Australasian Trials Group		https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=377668&isReview=trueEntriely new concept of alternating different ALK inhibitors in 4-8 week
cycles
40

11/27/2017

Stereotactic Body Radiotherapy for the Treatment of Oligo-Progressive Disease (HALT)II/III

Advanced NSCLC with actionable mutation receiving TKI
Confirmed oligo-progressive disease with 3 or fewer sites
Sites of progression are suitable for treatment with SBRT		UK: Sutton, Chelsea, Guildford, Manchester, Nottingham, Sheffield
Institute of Cancer Research, United Kingdom
NCT03256981

 		Randomized to SBRT + TKI or indicated TKI alone. Not clear if still recruiting
41
3/9/2017

Brigatinib after treatment with next generation ALK TKIs

II

ALK advanced or metastatic
Progression on Alectinib or Ceritinib
Progression on Brigatinib in some circumstances		USA: Denver, Durham NC, Nashville, Dallas

U of CO, Duke, Vanderbilt
UT Southwestern,
Criterium, Inc. Takeda		NCT02706626

Recruitment statsus listed as "unknown"
as of 1/9/2022
42
12/11/2014

Alectinib: Deciphering anti tumor response and resistance
with intratumor heterogenicity
(Darwin II)		II

ALK/RET gene fusion relapsed disease
Biopsy of relapsed disease
Multi-region sequencing of the primary tumor available		UK: London - University College Hospital

University College, London
Hoffman-La Roche
NCT02314481

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