Study of LP-184 in Patients With Advanced Solid Tumors

NCT05933265 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: LTRN184-1AST23-1
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 7

Brief Summary

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. Participants 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

Conditions

Advanced Solid Tumor; Metastatic Solid Tumor; GBM; NSCLC; TNBC - Triple-Negative Breast Cancer; Pancreatic Adenocarcinoma; DDR Gene Mutation

Keywords

LP-184; Phase 1; Lantern Pharma; Cancer; DNA damage repair

Outcome Measures

Primary Outcomes (3)

• To evaluate the safety and tolerability of LP-184 assessed by the incidence and severity of all adverse events graded by CTCAE v5.0

  12 months

• To determine the MTD of LP-184 based on all available safety (graded by CTCAE v5.0) and PK data.

  12 months

• To determine the RP2D of LP-184 based on all available safety (graded by CTCAE v5.0), PK, PD and efficacy data

  12 months

Secondary Outcomes (6)

• To characterize the PK of LP-184 and its metabolites in plasma by assessing the area under the plasma concentration versus time curve (AUC).

  Blood samples for PK analysis collected at multiple time points during cycle 1 (each cycle is 21 days)

• To characterize the PK of LP-184 and its metabolites in plasma by assessing the peak plasma concentration (Cmax)

  Blood samples for PK analysis collected at multiple time points during cycle 1 (each cycle is 21 days)

• To characterize the PK of LP-184 and its metabolites in plasma by assessing the time to peak plasma concentration (Tmax)

  Blood samples for PK analysis collected at multiple time points during cycle 1 (each cycle is 21 days)

• To characterize the PK of LP-184 and its metabolites in plasma by assessing the amount of time required for the drug concentration in plasma to be reduced to exactly half its starting concentration (half-life, t1/2)

  Blood samples for PK analysis collected at multiple time points during cycle 1 (each cycle is 21 days)

• To characterize the PK of LP-184 and its metabolites in plasma by assessing the apparent volume of distribution at steady state after non-intravenous administration (Vss/F)

  Blood samples for PK analysis collected at multiple time points during cycle 1 (each cycle is 21 days)

Study Arms (4)

Master Protocol

EXPERIMENTAL

A phase 1/2 dose escalation and cohort expansion study of LP-184 in patients with advanced or metastatic solid tumors. A BOIN design will be used to evaluate the safety of LP-184, determine the MTD, and identify the RP2D. 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.

Drug: LP-184

Supplement A

EXPERIMENTAL

Phase 1b/2 Expansion cohort of participants with triple negative breast cancer (TNBC), non-small cell lung cancer (NSCLC), pancreatic adenocarcinoma (PDAC) or other solid tumours with known DDR genomic alterations to determine the optimal dose/RP2D and to obtain preliminary estimates of clinical activity.

Drug: LP-184

Supplement C

EXPERIMENTAL

Phase 1b/2 Expansion cohort of participants with Hormone Receptor (HR)-Negative and HER2-Negative Breast Cancer (TNBC) to evaluate the safety, tolerability and clinical activity of LP-184 in combination with olaparib

Drug: LP-184; Drug: Olaparib

Supplement D

EXPERIMENTAL

Phase 1b/2 Expansion cohort of participants with KEAP1 and/or STK11-mutated and programmed cell death ligand-1 (PD-L1)-low NSCLC to evaluate the safety, tolerability and clinical activity of LP-184 in combination with nivolumab and ipilimumab in .

Drug: LP-184; Drug: Nivolumab & Ipilimumab

Interventions

LP-184 DRUG

LP-184 is a small molecule alkylating agent causing tumor cell death through DNA damage.

Master Protocol; Supplement A; Supplement C; Supplement D

Olaparib DRUG

A poly (ADP-ribose) polymerase (PARP) inhibitor that impairs homologous recombination (HR) dependent DNA damage repair by trapping PARP1/2 on DNA, leading to synthetic lethality in BRCA1/2-deficient cells.

Supplement C

Nivolumab & Ipilimumab DRUG

Nivolumab is monoclonal antibody and classified as an immune checkpoint inhibitor. By blocking the PD-1 receptor on the surface of T cells, Nivolumab restores immune cells' ability to recognize and attack cancer cells. Ipilimumab is monoclonal antibody and classified as an immune checkpoint inhibitor. By blocking the CTLA4 protein on the surface of T cells, Ipilimumab activates T-cells and allows T-cells to attack cancer cells.

Supplement D

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥18 years of age at the time of consent
• Provided signed written ICF and voluntary consent prior to any mandatory study-specific procedures, sampling, and analyses.
• 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.
• Note: patients with certain tumor types such as those with relatively high prevalence of DDR gene alterations and/or PTGR1 over expression (e.g., triple negative breast cancer, lung, prostate, ovarian, pancreatic, bladder, and GBM) may be preferentially enrolled in Phase 1a.
• ECOG performance status 0-1 or Karnofsky performance scale \>60 for GBM patients.
• Patients must have measurable disease per RECIST 1.1 or RANO 2.0 criteria as applicable.
• Note: patients without measurable disease may be eligible, following discussion with the investigator and the sponsor, if the patient presents with non-measurable but evaluable disease of any size unequivocally attributable to advanced solid tumor.
• Patients must have life expectancy \>3 months.
• Adequate organ function at screening defined as:
• Liver Function
• AST, ALT ≤3 x ULN or \<5 x ULN in cases of documented liver metastases or involvement of liver in the disease process.
• Total serum bilirubin ≤1.5 x ULN or \<5 x ULN if secondary to Gilbert's syndrome or documented liver metastases or involvement of liver in the disease process.
• Renal Function
• Serum creatinine clearance ≥60 mL/min either measured or calculated using standard Cockcroft-Gault formula.
• Serum electrolyte (potassium, calcium, and magnesium) levels within the normal reference range (may be supplemented according to institutional standard).

You may not qualify if:

• Exposure to anti-cancer therapy within 2 weeks or within at least 5 half-lives of the anticancer agent whichever is shorter; or 4 weeks from any biologics/immunotherapies or any investigational therapy prior to the first dose of LP-184.
• Any history of retinopathy and/or macular degeneration (without specifications or grades).
• Has received radiation within 4 weeks of Cycle 1 Day 1. Unless the tumor at the site of treatment continues to increase in size after the patient has completed radiotherapy treatment.
• Infection requiring antibiotics, antivirals, or antifungals within 1 week prior to first dose of study drug, unless such infection is adequately controlled (defined as exhibiting no ongoing signs/symptoms related to the infection and with clinical improvement). In the case of prophylactic use of these agents, discussion with the Medical Monitor is required prior to enrollment.
• Hepatitis B and/or hepatitis C infection (as detected by positive testing for hepatitis B surface antigen \[HbsAg\] or antibody to hepatitis C virus with confirmatory testing) or known seropositivity for or history of active viral infection with human immunodeficiency virus (HIV).
• Are pregnant or breastfeeding. (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).
• Have clinically significant cardiac disease including:
• New York Heart Association Class IV heart failure.
• Myocardial infarction or stroke ≤3 months prior to the first dose of LP-184.
• Unstable angina within ≤12 weeks prior to the first dose of LP-184 unless the underlying disease has been corrected by procedural intervention e.g., stent, bypass.
• Severe aortic stenosis.
• Uncontrolled arrhythmia. Sponsor approval of patients with arrhythmia is required.
• QTc \>470 ms by Fredericia criteria.
• Congenital long QT syndrome, or a QT interval corrected by Fridericia's formula (QTcF) \>470 ms (average of triplicate ECGs) at Screening and/or on Cycle 1 Day 1 (pre-dose) except for 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.
• Have clinically significant AEs that have not returned to baseline or ≤Grade 1 based on NCI-CTCAE prior to first dose of study drug, 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, alopecia, or hypothyroidism from prior immunotherapy treatment).

Sponsors & Collaborators

• Lantern Pharma Inc.: lead

Study Sites (7)

Highlands Oncology Group

Springdale, Arkansas, 72758, United States

Location

Indiana University Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

Norton Healthcare, Inc.

Louisville, Kentucky, 40205, United States

Location

John Hopkins - The Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, 21287, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

UT Health Science Center San Antonio

San Antonio, Texas, 78229, United States

Location

START Mountain Region

West Valley City, Utah, 84119, United States

Location

MeSH Terms

Conditions

Neoplasm Metastasis; Triple Negative Breast Neoplasms; Neoplasms

Interventions

olaparib; Nivolumab; Ipilimumab

Condition Hierarchy (Ancestors)

Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Breast Neoplasms; Neoplasms by Site; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Reggie Ewesuedo, MD

  Lantern Pharma Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: BOIN Design

Study Record Dates

• First Submitted: June 23, 2023
• First Posted: July 6, 2023
• Study Start: June 9, 2023
• Primary Completion (Estimated): July 28, 2026
• Study Completion (Estimated): July 28, 2026
• Last Updated: May 4, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (7)