PHase II Trial of LP-300 in Combination with CArboplatin and PemetRexed in Never SMOker Patients with Relapsed AdvaNced PrImary AdenoCarcinoma of the Lung After Treatment with Tyrosine Kinase Inhibitors

The purpose of this research is to see if LP-300 affects the survival of subjects who have never smoked but developed advanced lung cancer despite taking one or more targeted treatments against the lung cancer.

The first stage of the trial will examine the safety of LP-300 used in combination with standard cancer treatments (carboplatin and pemetrexed) in the first six subjects, in which all subjects will receive LP-300 with carboplatin and pemetrexed. In the second stage of the study, subjects will be assigned to one of the treatment arms by chance (like a coin-flip), with about 2 out of 3 subjects receiving the investigational drug, LP-300, along with standard cancer treatment, and 1 out of 3 subjects receiving standard cancer treatment alone. The major purpose of this stage of the trial is to determine if LP-300 in combination with standard treatment has a different effect on the cancer in subjects who have never smoked than the standard treatment alone in subjects who have never smoked.

This research is being performed because improvements are needed in the treatment management of subjects with cancer.

Inova Schar Cancer Institute
A division of Inova Fairfax Hospital
8081 Innovation Park Drive 
Fairfax, VA 22031

1. Patients with confirmed histopathological diagnosis of inoperable advanced (Stage III or IV)
primary adenocarcinoma (including bronchioalveolar cell carcinoma) of the lung with actionable genomic alterations (e.g., ROS1, MET exon14 skipping mutations, BRAF, ALK, EGFR, NTRK
fusions, etc.). If pathological or radiological findings are inconclusive for a diagnosis of primary
adenocarcinoma of the lung, additional studies must be performed to confirm primary lung versus
metastatic adenocarcinoma. Patients with no known actionable genomic alterations are ineligible
to enroll in the study.
2. Locally advanced inoperable or metastatic lung cancer.
3. Patients must be never smokers: a never smoker is an adult who has never smoked, or who has
smoked less than 100 cigarettes (or equivalent in other products such as vapes, cigars, pipes,
hookahs, and marijuana use) in his or her lifetime. Note: a patient with actionable genomic
alteration(s) who is a former smoker may be enrolled if such a patient would ordinarily be treated
with pemetrexed and carboplatin combination based on institutional standard clinical practice;
consultation with the sponsor's Medical monitor would be required
4. Patients who have received systemic treatment with tyrosine kinase inhibitors (TKIs) for non-small
cell lung cancer but have experienced disease progression, unacceptable TKI-related toxicities, or
are unable to tolerate the further use of TKIs.
5. Prior radiation therapy is allowed, provided (1) that at least one area of measurable tumor (by CT
scan with at least one target lesion) per RECIST Version 1.1 that has not been subject to prior
irradiation, and (2) that any such therapy is completed and any radiation-induced sequelae are
recovered at least 21 days before randomization.
6. Patients with an ECOG performance status of 0 or 1.
7. Patients who are at least 18 years of age.
8. Patients with documented stable CNS metastases with no cognitive deficits, or progressive sensory
or motor deficits, or seizures during the last 21 days prior to enrollment are eligible. Patients must
have discontinued anti-seizure medications and steroids at least 14 days prior to patient enrollment.
9. Patients must have fully recovered from any prior major surgical or diagnostic staging procedure
(e.g., thoracotomy, mediastinoscopy), and have a post-operative status of at least 30 days before
enrollment.
10. Patients must have adequate bone marrow, adequate hepatic function, and baseline creatinine levels
documented by specific laboratory criteria within 21 days prior to enrollment, including the
following:
• White blood cell count ≥ 2 x 109/L
• Absolute neutrophil count (ANC) ≥ 1.5  109/L
• Hemoglobin ≥ 10 g/dL
• Platelet count ≥ 100  109/L
• Total bilirubin < 1.5 x the upper limit of normal (ULN). For patients with Gilbert's syndrome,
total bilirubin < 2.5 x ULN
• Aspartate aminotransferase (AST/SGOT) ≤ 2.5  ULN
• Alanine aminotransferase (ALT/SGPT) ≤ 2.5  ULN
• Alkaline phosphatase ≤ 2.5  ULN
• Baseline serum creatinine level no greater than 1.5 mg/dL or 133 μmol/L.
• Creatinine clearance ≥ 45 mL/min as calculated using the Cockcroft-Gault methodology
(Cockcroft 1976)
• Magnesium ≥ 1.7 mg/dL
11. Female patients of child-bearing potential must have a negative pregnancy test and must agree to
use an acceptable contraceptive method during the study and for 12 weeks after their last dose of
study treatment. Male patients with partners of child-bearing potential must also agree to use an adequate method of contraception for the duration of the study and for 12 weeks after their last
dose of study treatment.
NOTE: a) A patient is considered of childbearing potential if she is biologically capable of having
children and is sexually active. Medically acceptable contraceptives include: (1) surgical sterilization
(such as a tubal ligation, hysterectomy, or vasectomy), (2) approved hormonal contraceptives (such as
birth control pills, patches, implants or injections), (3) barrier methods (such as a condom or diaphragm)
used with a spermicide (only if used in combination with another mentioned method), or (4) an
intrauterine device (IUD). Contraceptive measures and other medications sold for emergency use after
unprotected sex, are not acceptable methods for routine use. If a female patient becomes pregnant, study
therapy must be discontinued immediately. Lastly, b) the period for use of contraception after last dose of
pemetrexed or carboplatin should be determined by the domestic drug labels and/or institutional standard
clinical practice. For S Korea, contraception is to be used for 6 months after the last dose.
12. Patients must have been disease-free at least two years for other malignancies, excluding:
• Curatively-treated basal cell carcinoma,
• Ductal carcinoma in situ (DCIS) of the breast
• Non-melanomatous carcinoma of the skin, or
• Carcinoma in situ of the cervix.
13. Be willing to provide an archival tumor tissue sample, if available. The archival sample must be
from a tumor lesion that was not previously irradiated. Formalin-fixed, paraffin embedded (FFPE)
tissue blocks are preferred to slides. The sample must have been obtained less than 36 months prior
to consent.
14. Provide signed, written, IRB-approved informed consent prior to any screening procedures.

1. Patients with small cell, squamous cell, large cell, undifferentiated, mesothelioma, or any form of
mixed (e.g., small cell and adenocarcinoma or squamous and adenocarcinoma) histopathological
diagnosis of primary lung cancer.
2. Patients with metastatic adenocarcinoma arising from any primary site other than the lung.
3. Patients who have received any prior investigational agents except for investigational TKI drugs.
The minimum drug washout period for all TKIs, including approved and investigational, is ≥ 5
half-lives or 2 weeks, whichever is shorter.
4. Patients who have received chemotherapy and/or immunotherapy but transitioned to a TKI with
no evidence of disease progression will be allowed to enroll. Patients who experienced disease
progression while on chemotherapy and/or immunotherapy will be ineligible for the trial.
5. Patients taking medications that are sensitive substrates of CYP2C19 or P-gp transporters.
6. Patients with recent onset (within 6 months of randomization) of congestive heart failure (New
York Heart Association Classification Class II or greater), angina pectoris, unstable angina pectoris,
serious uncontrolled cardiac arrhythmias, myocardial infarction, stroke, or transient ischemic
attacks.
7. Have a corrected QT interval (using Fridericia's correction formula) (QTcF) of > 470 msec.
(average of triplicate ECGs) at Screening and/or on C1D1 (pre- dose) except for a documented
bundle branch block or unless secondary to pacemaker. In the case of a documented bundle
branch block or unless secondary to pacemaker. In the case of a documented bundle
branch block or a pacemaker, discussion with the Medical Monitor is required prior to
enrollment.

8. Patients with unstable CNS metastases (characterized by progressive sensory/motor impairment,
cognitive/speech impairment, or seizure activity) within 21 days before enrollment.
9. Patients who do not have at least one (1) measurable disease site that has not been previously
irradiated.
10. Patients who are known to be positive for human immunodeficiency virus (HIV), hepatitis B virus
surface antigen (HbsAg) or hepatitis C virus (HCV).
11. Patients with active infections, active interstitial lung disease, uncontrolled high blood pressure,
uncontrolled diabetes mellitus, uncontrolled seizures (not due to CNS metastases) within the last 3
months, or other serious underlying medical condition.
12. Patients with documented hypersensitivity to any of the study medications (LP-300, pemetrexed,
carboplatin and/or excipients) or supportive agents that may be used.
13. Patients who are pregnant or are breastfeeding.
14. Patients who have undergone blood transfusions within 10 days before randomization.
15. Any other medical intervention or other condition which, in the opinion of the Principal
Investigator, could compromise adherence to study requirements or confound the interpretation of
study results.
16. Patients who have a life expectancy of less than 3 months.