A Study of Lorlatinib and Ramucirumab for ALK-Positive Lung Cancer
This study is looking for people with metastatic (spread to other parts of the body) or recurrent (returned after treatment) non-small cell lung cancer that has an ALK fusion (a specific change in the cancer cells' genes). It combines two drugs, lorlatinib and ramucirumab, to see if they are safe together. Researchers will test different doses of lorlatinib with ramucirumab to find the dose that causes the fewest or mildest side effects. Once a safe dose is found, they will study if this combination helps treat ALK-rearranged NSCLC. The study also aims to understand if certain genes predict how well someone responds to this treatment. You must be over 18, have ALK fusion identified, and meet other health requirements to join. The study plans to enroll 56 participants.
- Study design
- This interventional study plans to enroll 56 participants. It will first determine the maximum tolerated dose of the drug combination.
- What's involved
- Not specified in the trial record.
- Compensation
- Not stated in the trial record.
- Follow-up
- The study will measure progression-free survival (how long you live without the cancer getting worse) for 12 months.
AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.
NCT06007937
A Study of Lorlatinib in Combination With Ramucirumab in People With Lung Cancer
Active, Not Recruiting
PHASE1Ages 19+InterventionalTreatmentMemorial Sloan Kettering Cancer CenterInvestigator-initiated
~9 participants
Updated 2026-08-13 on ClinicalTrials.gov
What's tested:LorlatinibRamucirumab
At a glance
Recruiting sites
0 of 6 listed sites are recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Maximum tolerated dose (MTD) (Phase I)
Measured over 1 year
+1 more outcome measured
Conditions
Where it's being run
6 sites across 2 statesNew York4
New Jersey2
Study leadership
- Gregory Riely, MD, PhD · PRINCIPAL_INVESTIGATOR · Memorial Sloan Kettering Cancer Center
Who to contact
This trial hasn't published a contact. View it on ClinicalTrials.gov
Do you actually qualify for this trial?
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Eligibility criteria
Inclusion
Written informed consent
Age \>18 years old
Metastatic or recurrent, biopsy-proven non-small cell lung cancer
ALK fusion identified by next generation sequencing (NGS) or IHC on material obtained from tumor or plasma
Measurable (RECIST 1.1) indicator lesion not previously irradiated
Karnofsky performance status (KPS) ≥ 70%
Adequate organ function defined as follows: ANC ≥1.5 × 10\^9 /L, platelets ≥100 × 10\^9/L, hemoglobin ≥ 9 g/dL, INR ≤ 1.5, PTT or aPTT \<1.5x ULN, total bilirubin ≤ 1.5 × ULN (Patients with Gilbert's syndrome with a total bilirubin ≤2.0 times ULN and direct bilirubin within normal limits are permitted), AST ≤ 3 × ULN, ALT ≤ 3 × ULN or ≤ 5 x ULN in the setting of liver metastases, Cr ≤1.5 ULN or CrCl ≥ 40 mL/min. If Cr is
Patients on full-dose anticoagulation must be on a stable dose of oral anticoagulant or low molecular weight heparin for a minimum of 14 days prior to trial enrollment without signs of active bleeding or pathological condition that carries a high risk of bleeding (eg, tumor invading major vessels or known varices). Patients on warfarin must have an INR ≤ 3.0
Patients must have recovered (Common Terminology Criteria for Adverse Events \[CTCAE\] version 5 Grade ≤1) from the acute effects of prior therapy, except for residual alopecia or peripheral neuropathy (up to grade 2 allowed)prior to start of therapy
Patients in cohort 1 will be treatment-naïve in the metastatic setting. Prior treatment with adjuvant chemotherapy is allowed
Patients in cohort 2 will have progressed or be intolerant of at least one second generation ALK TKI, including alectinib, brigatinib, or ceritinib.
Patients may have received multiple ALK TKIs as well as chemotherapy, but one of these treatments must have been with a second-generation ALK TKI.
Because the teratogenicity of ramucirumab is not known, the patient, if sexually active, must be postmenopausal, surgically sterile, or using effective contraception (hormonal or barrier methods).
Female patients of childbearing potential must have a negative serum pregnancy test within 7 days prior to first dose of protocol therapy.
Exclusion
Prior lorlatinib or ramucirumab exposure
Symptomatic, unstable brain metastasis requiring therapy with steroids or radiation therapy. Patients with clinically stable brain metastases (previously treated or untreated) are eligible
Women who are breastfeeding or pregnant
Major radiotherapy within 2 weeks of starting treatment on protocol
Major surgery within 4 weeks of starting treatment on protocol or minor surgery/subcutaneous venous access device placement within 7 days prior to the first dose of protocol therapy
Less than 3 weeks since previous chemotherapy, 4 weeks since immunotherapy, and 2 weeks from any investigational therapy
Significant bleeding disorders or grade ≥3 bleeding episode within 12 weeks prior to enrollment. Patients with history of gross hemoptysis (defined as bright red blood of ≥1/2 teaspoon) within 8 weeks prior to enrollment will be excluded
New or history of diagnosis of deep vein thrombosis (DVT) or pulmonary embolism (PE) or other significant thromboembolic event in the 12 weeks prior to first dose of protocol therapy. Patients with thromboembolic events diagnosed \>12 weeks prior to protocol therapy are eligible if on stable doses of anticoagulation as outlined above. Venous port or catheter thrombosis or superficial venous thrombosis are not considered significant events
GI perforation and/or fistula or bowel obstruction within 6 months or risk factors for perforation prior to enrollment
Child-Pugh B or greater cirrhosis or cirrhosis (any degree) and a history of hepatic encephalopathy or clinically meaningful ascites resulting from cirrhosis. Clinically meaningful ascites is defined as ascites from cirrhosis requiring diuretics or paracentesis
Uncontrolled hypertension, defined as systolic BP ≥160 mm Hg or diastolic BP ≥100 mm Hg, prior to initiating study treatment, despite hypertensive intervention
Serious or non-healing wound, ulcer or bone fracture within 28 days of enrollment
Radiologically documented evidence of major blood vessel invasion or encasement by cancer or radiographic evidence of intratumor cavitation
Active systemic bacterial infection (requiring intravenous \[IV\] antibiotics at time of initiating study treatment), fungal infection, or detectable viral infection (such as known human immunodeficiency virus positivity with known active hepatitis B or C \[for example, hepatitis B surface antigen positive\]. Screening is not required for enrollment.
Arterial thrombotic event or arterial thromboembolic event, including myocardial infarction, unstable angina, congestive heart failure ≥ NYHA class III, cerebrovascular accident or transient ischemic attack, within 6 months prior to enrollment
Planned elective or major surgery during the trial
Chronic therapy with any of the following within 7 days of enrollment:
Antiplatelet agents (such as clopidogrel, ticlopidine, dipyridamole, or anagrelide)
Aspirin up to 325 mg/day is permitted
Serious uncontrolled medical disorders or psychological conditions that would, in the opinion of the investigator, limit the patient's ability to complete the study or sign an informed consent document
Patients with unavoidable strong CYP3A inducer or inhibitor use (see table 15.4 for list of agents)
What this trial measures
- Maximum tolerated dose (MTD) (Phase I)1 year
Dose limiting toxicities using the NCI Common Terminology Criteria for Adverse Events Version 5 (NCI-CTCAE) will be used to grade toxicities during the trial.
- Progression-free survival (Phase II)12 months
by RECIST