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

• ClinicalTrials.gov Identifier: NCT05456256
• Recruitment Status: Recruiting
• First Posted: July 13, 2022
• Last Update Posted: May 16, 2024
• Sponsor: Lantern Pharma Inc.
• Information provided by (Responsible Party): Lantern Pharma Inc.

Tracking Information

• First Submitted Date: July 6, 2022
• First Posted Date: July 13, 2022
• Last Update Posted Date: May 16, 2024
• Actual Study Start Date: August 12, 2022
• Estimated Primary Completion Date: November 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 8, 2022)

• Progression-free survival (PFS) [ Time Frame: Through study completion, an average of 2 years ]
  Number of days or months from the date of randomization to the earliest of the documented disease progression based on the Response Evaluation Criteria in Solid Tumors (RECIST) V1.1 criteria
• Overall survival (OS) [ Time Frame: Through study completion, an average of 2 years ]
  Number of days or months between the randomization date and the date of death from all causes

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: July 8, 2022)

• Objective response rate (ORR) [ Time Frame: Through study completion, an average of 2 years ]
  Proportion of patients with the best overall response of complete response or partial response
• Duration of objective response (DOR) [ Time Frame: Through study completion, an average of 2 years ]
  Time when the complete response/partial response criteria are met (whichever is first recorded) until the first date that recurrent or progressive disease is documented
• Clinical benefit rate (CBR) [ Time Frame: Through study completion, an average of 2 years ]
  Proportion of patients with the best overall response of complete response or partial response or stable disease for at least 120 days

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of LP-300 With Carboplatin and Pemetrexed in Never Smokers With Advanced Lung Adenocarcinoma
• Official Title: 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 HARMONIC Study)
• Brief Summary: The goal of this clinical trial is to determine clinical advantages for LP-300 in combination with carboplatin and pemetrexed in the never smoker patient population. The primary objectives of this study are to determine progression-free survival (PFS) and overall survival (OS) in the study-defined patient population when LP-300 is co-administered with the standard of care chemotherapy drugs carboplatin and pemetrexed compared to carboplatin and pemetrexed alone. This has been designed as a multicenter, open label, phase II trial with 90 patients to be enrolled in the United States.
• Detailed Description: Patients who are never smokers with lung adenocarcinoma and have relapsed after treatment with tyrosine kinase inhibitors (TKIs) will be eligible for enrollment. The trial will proceed in two stages. In the safety lead-in stage, 6 patients will be enrolled and treated with the LP-300 co-administered in combination with carboplatin and pemetrexed. In the absence of any safety signals in these patients, the second stage of the trial protocol will begin. This second stage consists of randomizing patients in a 2:1 allocation ratio to one of two arms: investigational arm of carboplatin, pemetrexed, and LP-300 or the standard of care arm of carboplatin and pemetrexed. Treatment of both groups will be on Day 1 of a 21-day cycle. A total of 4 to 6 treatment cycles are planned (number of cycles determined by PI discretion), with the possibility of patients going into a pemetrexed maintenance phase afterwards.
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Adenocarcinoma of Lung
• Carcinoma, Non-Small-Cell Lung

Intervention

• Drug: LP-300
  LP-300: 18.4 g/m2 by intravenous (IV) infusion over 30 minutes, administered every 21 days for a total of 4 to 6 treatment cycles. The number of treatment cycles will be determined by PI discretion.
  Other Names:

  • Tavocept
  • BNP7787
  • Dimesna
• Drug: Pemetrexed
  Pemetrexed: 500 mg/m2 by intravenous (IV) infusion over 30 minutes, administered every 21 days for a total of 4 to 6 treatment cycles. After completion of the 4 to 6 cycles, patients will have the option to continue pemetrexed maintenance therapy until disease progression, unacceptable toxicity, or patient preference/physician discretion. The number of treatment cycles will be determined by PI discretion.
  Other Names:

  • Alimta
  • Pemfexy
• Drug: Carboplatin
  Carboplatin: area under the concentration-time curve 5 mg/mL per minute (AUC5) by intravenous (IV) infusion over 30 minutes, administered every 21 days for a total of 4 to 6 treatment cycles. The number of treatment cycles will be determined by PI discretion.
  Other Name: Paraplatin

Study Arms

• Experimental: LP-300 in Combination with Pemetrexed and Carboplatin

  LP-300 (investigational drug) + Pemetrexed and Carboplatin (standard of care chemotherapies)

  Dosing occurs on Day 1 of a 21-day cycle.

  Interventions:

  • Drug: LP-300
  • Drug: Pemetrexed
  • Drug: Carboplatin
• Active Comparator: Pemetrexed and Carboplatin (Standard of Care)

  Pemetrexed and Carboplatin Only (standard of care chemotherapies)

  Dosing occurs on Day 1 of a 21-day cycle.

  Interventions:

  • Drug: Pemetrexed
  • Drug: Carboplatin

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: July 8, 2022): 90
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: May 2025
• Estimated Primary Completion Date: November 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Patients with confirmed histopathological diagnosis of inoperable advanced (Stage III or IV) primary adenocarcinoma (including bronchioalveolar cell carcinoma) of the lung with specific actionable genomic alterations (e.g., mesenchymal epithelial transition (MET) exon14 skipping mutations, anaplastic lymphoma kinase (ALK), epidermal growth factor receptor (EGFR), neurotrophic tyrosine receptor kinase (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.
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 computed tomography (CT) scan with at least one target lesion) per Response Evaluation Criteria in Solid Tumors (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 Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
7. Patients who are at least 18 years of age.
8. Patients with documented stable central nervous system (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 10*9/L
    • Absolute neutrophil count (ANC) ≥ 1.5 x 10*9/L
    • Hemoglobin ≥ 10 g/dL
    • Platelet count ≥ 100 x 10*9/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/ serum glutamic oxaloacetic transaminase (AST/SGOT) ≤ 2.5 x ULN
    • Alanine aminotransferase/ serum glutamic pyruvic transaminase (ALT/SGPT) ≤ 2.5 x ULN
    • Alkaline phosphatase ≤ 2.5 x 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: 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, (4) an intrauterine device (IUD), or (5) avoiding sexual activity that could cause you or your partner to become pregnant. 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.

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, Institutional Review Board (IRB) approved informed consent prior to any screening procedures.

Exclusion Criteria:

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
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 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Lyza Trejo; 972-277-1136; lyza@lanternpharma.com

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05456256
• Other Study ID Numbers: LTRN300-2LC01-OR21
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Lantern Pharma Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Lantern Pharma Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Reggie Ewesuedo, MD; Lantern Pharma Inc.

• PRS Account: Lantern Pharma Inc.
• Verification Date: May 2024