A Study of Lorlatinib in Combination With Ramucirumab in People With Lung Cancer

Trial number:
NCT06007937
Trial phase:
1, 2
Study type:
Biomarker, Targeted therapy
Overall status:
Recruiting

Study start date

August, 2023

Scientific title

A Phase 1/2 Study of Combination Lorlatinib and Ramucirumab in Patients With Advanced ALK-rearranged Lung Cancers

Summary

This study will test the safety of the combination of ramucirumab and lorlatinib. The researchers will test one or two different doses of lorlatinib in combination with ramucirumab to find the drug combination dose that causes few or mild side effects in participants. Once the researchers find this dose, they can test it in future participants to see if it is effective in treating their metastatic ALK-rearranged NSCLC. The researchers are also looking to see whether there are specific genes or DNA sequences associated with a response to treatment with lorlatinib and ramucirumab.

* 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

≥ 1.5x ULN, a 24-hr urine collection to calculate creatinine clearance must be performed

°The patient's urinary protein is ≤1+ on dipstick or routine urinalysis (UA); if urine dipstick or routine analysis is ≥2+, a 24-hour urine collection for protein must demonstrate \<1000 mg of protein in 24 hours to allow participation in this protocol).* 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.

Study design

Primary purpose: TREATMENT, Allocation: NA, Intervention model: SEQUENTIAL, Masking: NONE,

Conditions

Non Small Cell Lung Cancer, Metastatic, Recurrent

Other study ID numbers

23-131

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