Lung CancerPhase 2NSCLCNCT05948462
Lorlatinib in Combination With Chemotherapy in Participants With Metastatic Anaplastic Lymphoma Kinase Positive (ALK+) Non-small Cell Lung Cancer (NSCLC) Who Progressed on Single-agent Lorlatinib
A Phase 2 study testing Lorlatinib, Cisplatin or Carboplatin and Pemetrexed in people with Lung Cancer and Non-small Cell Lung Cancer, run by SCRI Development Innovations, LLC at 5 sites in United States.
Trial summary
This clinical trial is an open-label, single arm study evaluating the safest dose of lorlatinib in combination with standard of care chemotherapy in participants with metastatic anaplastic lymphoma kinase positive (ALK+) NSCLC who progressed on prior therapy of lorlatinib alone. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lung Cancer, Non-small Cell Lung Cancer
- What is being tested?
- Lorlatinib, Cisplatin or Carboplatin and Pemetrexed
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 5 sitesUnited States
- Study dates
- Nov 2023to Sep 2025
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Written informed consent, according to local guidelines, signed and dated by the participant or by a legal guardian prior to the performance of any study-specific procedures, sampling, or analyses
- At least 18 years-of-age at the time of signature of the informed consent form (ICF)
- Metastatic ALK+ NSCLC
- Clinical and/or radiological progressive disease while receiving lorlatinib monotherapy or within 3 weeks of stopping lorlatinib monotherapy due to clinical and/or radiological progressive disease
- Adequate hematologic function defined as:
- Absolute neutrophil count (ANC) ≥1500/μL
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- Hemoglobin (Hb) ≥9 g/dL
- Platelets ≥100,000/μL
- Adequate liver function defined as:
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 × the upper limit of normal (ULN)
- Total bilirubin ≤1.5 × ULN (Participants with known Gilbert disease: serum bilirubin level ≤ 3 × ULN)
- Adequate renal function defined as calculated creatinine clearance ≥45 mL/min as calculated by Cockcroft and Gault Formula
- Male or female participants. Male participants with female partners of childbearing potential and female participants of childbearing potential are required to use two forms of acceptable contraception, including one barrier method, during their participation in the study and for 90 days following last dose. Male participants must also refrain from donating sperm during their participation in the study.
Who cannot join
- Prior treatment with platinum-based standard of care doublet chemotherapy with pemetrexed
- ECOG Performance Status score ≥3
- Current treatment with any of the following:
- Known strong CYP3A inhibitors (e.g., atazanavir, boceprevir, clarithromycin, conivaptan, indinavir, itraconazole, ketoconazole, lopinavir, mibefradil, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telaprevir, telithromycin, troleandomycin, voriconazole, grapefruit juice or grapefruit/grapefruit-related citrus fruits [e.g., Seville oranges, pomelos]). The topical use of these medications (if applicable), such as 2% ketoconazole cream, is allowed.
- Known strong CYP3A inducers (e.g., avasimibe, carbamazepine, phenobarbital, phenytoin, rifatutin, rifampin, St. John's Wort)
- CYP3A substrates with a narrow therapeutic index (e.g., alfentanil, cyclosporine, dihydroergotamine, ergotamine, fentanyl including transdermal patch, pimozide, quinidine, sirolimus, tacrolimus) within 12 days prior to the first dose of lorlatinib
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- Known P-gp substrates with a narrow therapeutic index (e.g., digoxin)
- Currently receiving treatment with therapeutic doses of warfarin sodium. Low- molecular-weight heparin is allowed.
- Major surgery (excluding placement of vascular access) within 4 weeks of first dose of study drug(s).
- Has any history of ILD (including pulmonary fibrosis or radiation pneumonitis), has clinically significant ILD, or is suspected to have such disease by imaging during screening. If imaging findings are unlikely to indicate a history of pneumonitis, then the Investigator should discuss the considerations with the Study Chair about potential enrollment and record the reasoning in the source documentation.
- Clinically severe pulmonary compromise (based on Investigator's assessment) resulting from intercurrent pulmonary illnesses including, but not limited to:
- any underlying pulmonary disorder (e.g., severe asthma, severe chronic obstructive pulmonary disease, restrictive lung disease)
- any autoimmune, connective tissue or inflammatory disorder with pulmonary involvement (e.g., rheumatoid arthritis, Sjögren's syndrome, sarcoidosis) OR prior pneumonectomy
- Women who are pregnant, nursing, or plan to become pregnant while in the study and for at least 6 months after the last administration of study treatment
- Men who plan to father a child while in the study and for at least 3 months after the last administration of study treatment
- Presence of active gastrointestinal disease or other condition that will interfere significantly with the absorption, distribution, metabolism, or excretion of lorlatinib (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea Grade ≥2, malabsorption syndrome)
- Any of the following cardiac criteria:
- Any clinically important abnormalities (as assessed by the Investigator) in rhythm, conduction, or morphology of resting electrocardiograms (ECGs), e.g., complete left bundle branch block, third-degree heart block
- Congestive heart failure (New York Heart Association ≥ Grade 2)
- Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years-of-age, or any concomitant medication known to prolong the QT interval
- Second degree or third-degree AV block (unless paced) or any AV block with PR >220 msec
- As judged by the Investigator, any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension, uncontrolled diabetes mellitus, active bleeding diatheses, or active infection, including hepatitis B, hepatitis C, and human immunodeficiency virus. Screening for chronic conditions is not required.
- Presence of other active invasive cancers other than the one treated in this study within 5 years prior to screening, except appropriately treated basal cell carcinoma of the skin, in situ carcinoma of uterine cervix, or other local tumors considered cured by local treatment
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Messino Cancer Center
Asheville, North Carolina, 28806
Texas Oncology
Dallas, Texas, 75246
Sarah Cannon Research Institute at HealthONE
Denver, Colorado, 80218
Tennessee Oncology
Nashville, Tennessee, 37203
Virginia Oncology Associates
Norfolk, Virginia, 23502
About this study
Official title: Phase II Study of Lorlatinib in Combination With Chemotherapy in Participants With Metastatic Anaplastic Lymphoma Kinase Positive (ALK+) Non-small Cell Lung Cancer (NSCLC) Who Progressed on Single-agent Lorlatinib
This clinical trial is an open-label, single arm study evaluating the safest dose of lorlatinib in combination with standard of care chemotherapy in participants with metastatic anaplastic lymphoma kinase positive (ALK+) NSCLC who progressed on prior therapy of lorlatinib alone. The main goals of this study are to:
- Evaluate the safety and tolerability of lorlatinib in combination with standard of care chemotherapy.
- Evaluate how well the combination of lorlatinib and standard of care chemotherapy works to treat metastatic anaplastic lymphoma kinase positive (ALK+) NSCLC.
- Evaluate the pharmacokinetics (PK) of lorlatinib when given in combination with standard of care chemotherapy.
Read the detailed description
Lorlatinib is a kinase inhibitor with in vitro activity against ALK and ROS1. This study's aim is to evaluate the safety of lorlatinib given in combination with platinum-based standard of care chemotherapy in participants with metastatic anaplastic lymphoma kinase positive (ALK+) non-small-cell lung cancer who progressed after receiving lorlatinib alone.
There will be a lead-in portion for the first six participants treated. Lead-in participants will receive an assigned starting dose of lorlatinib by mouth once daily throughout each cycle. In addition, a platinum-based standard of care chemotherapy regimen, to include carboplatin or cisplatin as well as pemetrexed, will be given intravenously every 3 weeks. A cycle is defined as 3 weeks. After tolerability is confirmed in the lead-in with the first 6 participants on trial, the next 9 participants may begin at an increased starting dose of lorlatinib by mouth once daily. After 4 cycles of oral lorlatinib and intravenous platinum-based standard of care chemotherapy and intravenous pemetrexed, the participant will move into the maintenance regimen. The maintenance regimen will include continuing on daily oral lorlatinib plus intravenous pemetrexed every 3 weeks until disease progression or intolerable toxicity or other reason for discontinuation.
- Conditions
- Lung Cancer, Non-small Cell Lung Cancer
- Being tested
- Lorlatinib, Cisplatin or Carboplatin, Pemetrexed
- Keywords
- ALK positive, ALK+, Metastatic, Lung, NSCLC, Non-small cell lung cancer, Lorlatinib, Small molecule kinase inhibitor, Pemetrexed, Carboplatin, Cisplatin
- Medical subject headings
- Lung Neoplasms, Carcinoma, Non-Small-Cell Lung, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LorlatinibDrug
Also called Lorbrena, Lorviqua
Participants will receive assigned dose of daily oral lorlatinib continuously for each cycle. Each cycle is 3 weeks.
Cisplatin or CarboplatinDrug
Also called Platinol (Cisplatin), Paraplatin (Carboplatin)
Participants will receive standard of care intravenous Cisplatin or Carboplatin, both chemotherapy medications, on day 1 of each cycle every 3 weeks, for Cycles 1-4. Each cycle is 3 weeks.
PemetrexedDrug
Also called Alimta, Pemfexy, Ciambra
Participants will receive intravenous Pemetrexed, a chemotherapy medication, on day 1 of each cycle. Each cycle is 3 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Lorlatinib and Platinum and Pemetrexed | Experimental | Lorlatinib will be administered by mouth daily plus Pemetrexed by IV infusion every 3 weeks until progression or intolerable toxicity. Platinum-based standard of care chemotherapy by IV infusion will also be given every 3 weeks for the first 4 cycles; carboplatin or cisplatin are the platinum agents that may be selected based on physician discretion. One cycle is defined as 3 weeks. Receives: Drug: Lorlatinib; Drug: Cisplatin or Carboplatin; Drug: Pemetrexed |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of adverse and serious adverse events of lorlatinib in combination with standard of care platinum-based chemotherapy and pemetrexed as assessed by CTCAE v5.0.
Measured: From Cycle 1 Day 1 to 30 days after treatment discontinuation, up to approximately 1 year. Each cycle is 3 weeks.
Secondary outcomes (2)
Pharmacokinetic (PK) analysis: lowest concentration with steady state dosing interval (Css, min) of lorlatinib in combination with standard of care platinum-based chemotherapy and pemetrexed.
Measured: Cycle 1, Day 1; Cycle 2, Day 1; Cycle 4, Day 1 (each cycle is 3 weeks) and at time of treatment discontinuation, up to approximately 1 year.
Objective Response Rate (ORR) to assess the anti-tumor activity of treatment with lorlatinib in combination with standard of care platinum-based chemotherapy and pemetrexed.
Percentage of participants demonstrating a Complete Response (CR) or Partial Response (PR) according to RECIST v1.1 criteria
Measured: Up to approximately 26 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jul 2023
- Study startNov 2023 (estimated)
- Primary completionMar 2025 (estimated)
- Study completionSep 2025 (estimated)
Why it stopped: Study withdrawn by pharmaceutical funding partner
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Lung CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- SCRI Development Innovations, LLC
- Sponsor type
- University, hospital or other
- Collaborators
- Pfizer
- Responsible party
- Sponsor
- Investigators
- Melissa Johnson, MD, Study chair, SCRI Development Innovations, LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05948462
- Sponsor's protocol ID
- LUN 481
- Acronym
- NSCLC
- Status last verified
- Dec 2023
- First submitted
- 27 Jun 2023
- Last updated
- 13 Dec 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of Lorlatinib in Combination With Chemotherapy in Participants With Metastatic Anaplastic Lymphoma Kinase Positive (ALK+) Non-small Cell Lung Cancer (NSCLC) Who Progressed on Single-agent Lorlatinib
- ClinicalTrials.gov ID
- NCT05948462
- Acronym / sponsor ID
- NSCLC / LUN 481
- Conditions
- Lung Cancer, Non-small Cell Lung Cancer
- Keywords
- ALK positive, ALK+, Metastatic, Lung, NSCLC, Non-small cell lung cancer, Lorlatinib, Small molecule kinase inhibitor
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Study withdrawn by pharmaceutical funding partner
- Enrolment
- 0 participants (actual)
- Lead sponsor
- SCRI Development Innovations, LLCUniversity, hospital or other
- Collaborators
- Pfizer
- Study start
- Nov 2023 (estimated)
- Primary completion
- Mar 2025 (estimated)
- Study completion
- Sep 2025 (estimated)
- First posted
- 17 Jul 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This clinical trial is an open-label, single arm study evaluating the safest dose of lorlatinib in combination with standard of care chemotherapy in participants with metastatic anaplastic lymphoma kinase positive (ALK+) NSCLC who progressed on prior therapy of lorlatinib alone. The main goals of this study are to:
- Evaluate the safety and tolerability of lorlatinib in combination with standard of care chemotherapy.
- Evaluate how well the combination of lorlatinib and standard of care chemotherapy works to treat metastatic anaplastic lymphoma kinase positive (ALK+) NSCLC.
- Evaluate the pharmacokinetics (PK) of lorlatinib when given in combination with standard of care chemotherapy.
Detailed description
Lorlatinib is a kinase inhibitor with in vitro activity against ALK and ROS1. This study's aim is to evaluate the safety of lorlatinib given in combination with platinum-based standard of care chemotherapy in participants with metastatic anaplastic lymphoma kinase positive (ALK+) non-small-cell lung cancer who progressed after receiving lorlatinib alone.
There will be a lead-in portion for the first six participants treated. Lead-in participants will receive an assigned starting dose of lorlatinib by mouth once daily throughout each cycle. In addition, a platinum-based standard of care chemotherapy regimen, to include carboplatin or cisplatin as well as pemetrexed, will be given intravenously every 3 weeks. A cycle is defined as 3 weeks. After tolerability is confirmed in the lead-in with the first 6 participants on trial, the next 9 participants may begin at an increased starting dose of lorlatinib by mouth once daily. After 4 cycles of oral lorlatinib and intravenous platinum-based standard of care chemotherapy and intravenous pemetrexed, the participant will move into the maintenance regimen. The maintenance regimen will include continuing on daily oral lorlatinib plus intravenous pemetrexed every 3 weeks until disease progression or intolerable toxicity or other reason for discontinuation.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Lorlatinib and Platinum and Pemetrexed | Experimental | Drug: Lorlatinib, Drug: Cisplatin or Carboplatin, Drug: PemetrexedLorlatinib will be administered by mouth daily plus Pemetrexed by IV infusion every 3 weeks until progression or intolerable toxicity. Platinum-based standard of care chemotherapy by IV infusion will also be given every 3 weeks for the first 4 cycles; carboplatin or cisplatin are the platinum agents that may be selected based on physician discretion. One cycle is defined as 3 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Written informed consent, according to local guidelines, signed and dated by the participant or by a legal guardian prior to the performance of any study-specific procedures, sampling, or analyses
- At least 18 years-of-age at the time of signature of the informed consent form (ICF)
- Metastatic ALK+ NSCLC
- Clinical and/or radiological progressive disease while receiving lorlatinib monotherapy or within 3 weeks of stopping lorlatinib monotherapy due to clinical and/or radiological progressive disease
- Adequate hematologic function defined as:
Key exclusion criteria (23 listed)
- Prior treatment with platinum-based standard of care doublet chemotherapy with pemetrexed
- ECOG Performance Status score ≥3
- Current treatment with any of the following:
- Has any history of ILD (including pulmonary fibrosis or radiation pneumonitis), has clinically significant ILD, or is suspected to have such disease by imaging during screening. If imaging findings are unlikely to indicate a history of pneumonitis, then the Investigator should discuss the considerations with the Study Chair about potential enrollment and record the reasoning in the source documentation.
- Clinically severe pulmonary compromise (based on Investigator's assessment) resulting from intercurrent pulmonary illnesses including, but not limited to:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LorlatinibAlso: Lorbrena, LorviquaParticipants will receive assigned dose of daily oral lorlatinib continuously for each cycle. Each cycle is 3 weeks. | Drug | Lorlatinib and Platinum and Pemetrexed |
| Cisplatin or CarboplatinAlso: Platinol (Cisplatin), Paraplatin (Carboplatin)Participants will receive standard of care intravenous Cisplatin or Carboplatin, both chemotherapy medications, on day 1 of each cycle every 3 weeks, for Cycles 1-4. Each cycle is 3 weeks. | Drug | Lorlatinib and Platinum and Pemetrexed |
| PemetrexedAlso: Alimta, Pemfexy, CiambraParticipants will receive intravenous Pemetrexed, a chemotherapy medication, on day 1 of each cycle. Each cycle is 3 weeks. | Drug | Lorlatinib and Platinum and Pemetrexed |
Primary outcome
Incidence of adverse and serious adverse events of lorlatinib in combination with standard of care platinum-based chemotherapy and pemetrexed as assessed by CTCAE v5.0.
Time frame: From Cycle 1 Day 1 to 30 days after treatment discontinuation, up to approximately 1 year. Each cycle is 3 weeks.
2 secondary outcomes
Pharmacokinetic (PK) analysis: lowest concentration with steady state dosing interval (Css, min) of lorlatinib in combination with standard of care platinum-based chemotherapy and pemetrexed.
Time frame: Cycle 1, Day 1; Cycle 2, Day 1; Cycle 4, Day 1 (each cycle is 3 weeks) and at time of treatment discontinuation, up to approximately 1 year.
Objective Response Rate (ORR) to assess the anti-tumor activity of treatment with lorlatinib in combination with standard of care platinum-based chemotherapy and pemetrexed.
Time frame: Up to approximately 26 months
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Dec 2023.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Melissa Johnson, MD study chair
SCRI Development Innovations, LLC
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Lorlatinib, Cisplatin or Carboplatin and Pemetrexed in people with Lung Cancer and Non-small Cell Lung Cancer, run by SCRI Development Innovations, LLC at 5 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 13 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of adverse and serious adverse events of lorlatinib in combination with standard of care platinum-based chemotherapy and pemetrexed as assessed by CTCAE v5.0. (time frame: From Cycle 1 Day 1 to 30 days after treatment discontinuation, up to approximately 1 year. Each cycle is 3 weeks.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Dec 2023.