Study of LP-184 in Patients With Advanced Solid Tumors

A Phase 1A Dose Escalation Study of LP-184 in Patients With Advanced or Metastatic Solid Tumors.

The primary objective of this study is to evaluate the safety, tolerability, MTD and RP2D of LP-184 in patients with advanced solid tumors who have relapsed from or are refractory to standard therapy or for whom no standard therapy is available. The secondary objectives are to characterize the PK of LP-184 and its metabolites in plasma and assess clinical activity of LP-184.

Study Overview

• Status: Recruiting
• Conditions: Advanced Solid Tumor
• Intervention / Treatment: Drug: LP-184

Detailed Description

Patients who meet all eligibility criteria will be enrolled to receive treatment with LP-184 at a dose determined based on the available cohort at the time of each patient's enrollment. Patients will receive LP-184 infusion during Day 1 and Day 8 of each 21-day cycle, for a minimum of two cycles. Patients will be monitored for safety, PK, and clinical activity. Dose escalation is planned with minimum of 3 patient cohorts (starting at dose level 1). After selection of the maximum tolerated dose (MTD), additional patients will be enrolled at two dose levels, including the MTD, as determined by the Safety Review Committee, until at least 10 patients each are treated at each dose to determine the recommended phase 2 dose.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Ernest Kitt; Phone Number: 9725884183; Email: ekitt@lanternpharma.com
• Study Contact Backup: Name: Lyza Trejo; Email: lyza@lanternpharma.com

Study Locations

• United States
  • Arkansas
    • Springdale, Arkansas, United States, 72758
      • Recruiting
      • Highlands Oncology Group
      • Contact: Amie Winn; Phone Number: 479-502-9289; Email: Awinn@hogonc.com
      • Principal Investigator: Joseph T Beck
  • California
    • Los Alamitos, California, United States, 90720
      • Recruiting
      • Cancer and Blood Specialty Clinic
      • Contact: Trong Nguyen; Phone Number: 562-735-0602; Email: tnguyen@cbsclinic.com
      • Principal Investigator: Vu Phan, MD
      • Contact: Stefi Guillen; Email: sguillen@cbs.com
      • Sub-Investigator: Nihal Abdulla, MD
  • Illinois
    • Rolling Meadows, Illinois, United States, 60008
      • Recruiting
      • Northwest Oncology & Hematology
      • Contact: Nowsheen Azeemuddin; Phone Number: 847-577-0620; Email: nowsheena@northwestoncology.com
      • Principal Investigator: Bruce Bank, MD
      • Sub-Investigator: Marina Messinger, MD
      • Sub-Investigator: Gary E Kay, MD
      • Sub-Investigator: Ronald J Shade, MD
      • Sub-Investigator: Tonia Cabai, NP-C
      • Sub-Investigator: Cristyn Savoia, APN
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Recruiting
      • Indiana University Melvin and Bren Simon Cancer Center
      • Contact: Cassandra Brass; Email: cassbass@iu.edu
      • Principal Investigator: Misty Shields
  • Kentucky
    • Louisville, Kentucky, United States, 40205
      • Recruiting
      • Norton Healthcare, Inc.
      • Principal Investigator: John Hamm
      • Contact: Michael Buchanan; Phone Number: 19472 502-629-2500; Email: Michael.Buchanan@nortonhealthcare.org
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111
      • Recruiting
      • Fox Chase Cancer Center
      • Principal Investigator: Anthony Olszanski, MD
      • Contact: Ikenna Opurum; Phone Number: 267-418-6160; Email: ikenna.opurum@fccc.edu
  • Utah
    • West Valley City, Utah, United States, 84119
      • Recruiting
      • START Mountain Region
      • Contact: Casey Larsen; Phone Number: 801-907-4752; Email: casey.larsen@startthecure.com
      • Principal Investigator: William McKean, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Patient Inclusion Criteria:

1. ≥18 years of age
2. Provided signed written ICF and voluntary consent prior to any mandatory study-specific procedures, sampling, and analyses.
3. Resolved acute effects of any prior therapy to baseline severity or ≤Grade 1 NCI CTCAE except for AEs not constituting a safety risk by investigator judgment.
4. Have a histologically or cytologically documented advanced solid tumor that has relapsed from or is refractory to standard treatment, or for which no standard treatment is available.
5. ECOG performance status 0-1 or Karnofsky performance scale >60 for GBM patients.
6. Patients must have measurable disease per RECIST 1.1 or RANO criteria as applicable.
7. Patients must have life expectancy >3 months.
8. Adequate Liver, renal, bone marrow, and coagulation function as determined at screening.

9. For CNS disease considerations, based on screening contrast brain MRI, patients must have 1 of the following:

   • No evidence of brain metastases
   • Untreated brain metastases not needing immediate local therapy. For patients with untreated CNS lesions >2.0 cm on screening contrast brain MRI, discussion with and approval from the medical monitor is required prior to enrollment.
   • Previously treated brain metastases. Patients on a chronic stable dose of ≤2 mg total daily of dexamethasone (or equivalent) are eligible with discussion and approval by the medical monitor.

Patients treated with CNS local therapy for newly identified lesions found on contrast brain MRI performed during study screening are eligible to enroll if all of the following criteria are met:

• Time since whole brain radiation therapy was ≥21 days prior to first dose of LP-184,
• Time since stereotactic radiosurgery was ≥7 days prior to first dose of LP-184, or
• Time since surgical resection was ≥28 days.
• Other sites of disease assessable by RECIST v1.1 are present.

Patient Exclusion Criteria:

1. Exposure to anti-cancer therapy within 2 weeks or within at least 5 half-lives whichever is shorter; or 4 weeks from any biologics/immunotherapies or any investigational therapy prior to the first dose of LP-184.
2. History of retinopathy and/or macular degeneration.
3. Has received radiation within 4 weeks of Cycle 1 Day 1.
4. Have acute and severe bacterial, viral, or fungal infection.

5. Known or demonstrated viral infection as listed below:

   1. Seropositivity for HIV (only if required by local regulations).
   2. Hepatitis B and/or hepatitis C infection (as detected by positive testing for hepatitis B surface antigen or antibody to hepatitis C virus with confirmatory testing).
6. Are pregnant or breastfeeding.
7. Have clinically significant cardiac disease as determined at screening.
8. Have clinically significant AEs that have not returned to baseline or ≤Grade 1 based on NCI-CTCAE unless approved by the sponsor. Patients with chronic Grade 2 toxicities may be eligible per the discretion of the investigator and sponsor (e.g., Grade 2 chemotherapy-induced neuropathy or hypothyroidism from prior immunotherapy treatment).
9. Have had major surgery (requiring general anesthesia) within ≤4 weeks of first dose of LP-184.
10. Have any other serious medical condition which, in the opinion of the investigator, would preclude the patient from study participation.
11. Have clinically active brain metastases, defined as untreated and symptomatic, or requiring therapy with steroids or anticonvulsants to control associated symptoms. Patients with treated brain metastases that are no longer symptomatic and who require no treatment with steroids may be included in the study if they have recovered from the acute toxic effect of radiotherapy. A minimum of 3 weeks must have elapsed between the end of whole brain radiotherapy and study enrollment (1 week for stereotactic radiotherapy).

12. For patients with CNS metastatic disease, based on screening brain MRI, patients must not have:

    • Any untreated brain lesions >2.0 cm in size, unless medical monitor approved enrollment.
    • Ongoing use of systemic corticosteroids for control of symptoms of brain metastases at a total daily dose of >2 mg of dexamethasone (or equivalent).
    • Patients on a chronic stable dose of ≤2 mg total daily of dexamethasone (or equivalent) are eligible with discussion and approval by the medical monitor.
    • Any brain lesion thought to require immediate local therapy, including (but not limited to) a lesion in an anatomic site where an increase in size or possible treatment-related edema may pose a risk to the patient (e.g., brain stem lesions). Patients who underwent local treatment for such lesions identified by screening contrast brain MRI may still be eligible based on criteria described under CNS inclusion criteria described above.
    • Known or suspected leptomeningeal disease as documented by the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1 Single Arm Multicenter Study to Assess the Safety and Tolerability of LP-184; Phase 1 Single Arm Multicenter Study to Assess the Safety and Tolerability of LP-184 in Patients with Advanced Solid Tumors	Drug: LP-184; LP-184 is a small molecule alkylating agent causing tumor cell death through DNA damage.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and severity of AEs	Incidence and severity of AEs graded according to the NCI CTCAE, version 5.0, clinical laboratory and ECG abnormalities defined as DLTs	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Plasma Concentration of LP-184 (Cmax)	To determine the Cmax from plasma concentration in patients	Blood samples for PK analysis collected at multiple time points during cycle 1 (each cycle is 21 days)
Time to maximum plasma concentration of LP-184 (Tmax)	To determine the Tmax from plasma concentration in patients	Blood samples for PK analysis collected at multiple time points during cycle 1 (each cycle is 21 days)
Half-life of LP-184 [if data permits (T1/2)]	To determine the half-life of LP-184 in patients	Blood samples for PK analysis collected at multiple time points up to 24 hours post infusion during cycle 1 (each cycle is 21 days)
Area under the Plasma Concentration versus Time Curve (AUC) of LP-184 and major metabolite	Area under the Plasma Concentration versus Time Curve (AUC) of LP-184 and major metabolite from time zero to 24 hours post infusion (AUC 0 to 24)	Blood samples for PK analysis collected at multiple time points up to 24 hours post infusion during cycle 1 (each cycle is 21 days)

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): June 9, 2023
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): June 9, 2025

Study Registration Dates

• First Submitted: June 23, 2023
• First Submitted That Met QC Criteria: July 3, 2023
• First Posted (Actual): July 6, 2023

Study Record Updates

• Last Update Posted (Actual): January 25, 2024
• Last Update Submitted That Met QC Criteria: January 24, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Cancer; Phase 1; DNA damage repair; LP-184; Lantern Pharma
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: LTRN184-1AST23-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No