Study of LP-184 in Patients With Advanced Solid Tumors

NCT ID: NCT05933265

Last Updated: 2025-03-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

175 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-06-09

Study Completion Date

2025-09-09

Brief Summary

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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

Detailed Description

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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.

Conditions

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

Study Design

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Allocation Method

NA

Intervention Model

SEQUENTIAL

BOIN Design
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Master Protocol

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.

Group Type EXPERIMENTAL

LP-184

Intervention Type DRUG

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

Supplement A

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.

Group Type EXPERIMENTAL

LP-184

Intervention Type DRUG

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

Supplement B

Phase 1b/2 Expansion cohort of participants with recurrent GBM to evaluate the safety, pharmacokinetics and preliminary anti-tumour activity of LP-184 alone and in combination with spironolactone.

Group Type EXPERIMENTAL

LP-184

Intervention Type DRUG

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

Spironolactone

Intervention Type DRUG

A competitive mineralocorticoid receptor antagonist that inhibits aldosterone-dependent sodium reabsorption/ potassium excretion and lowering blood pressure, as well as degrades the transcription coupled nucleotide excision repair protein ERCC3 to impair DNA repair.

Supplement C

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

Group Type EXPERIMENTAL

LP-184

Intervention Type DRUG

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

Olaparib

Intervention Type 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.

Interventions

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LP-184

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

Intervention Type DRUG

Spironolactone

A competitive mineralocorticoid receptor antagonist that inhibits aldosterone-dependent sodium reabsorption/ potassium excretion and lowering blood pressure, as well as degrades the transcription coupled nucleotide excision repair protein ERCC3 to impair DNA repair.

Intervention Type DRUG

Olaparib

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.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. ≥18 years of age at the time of consent
2. Provided signed written ICF and voluntary consent prior to any mandatory study-specific procedures, sampling, and analyses.
3. 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.
4. ECOG performance status 0-1 or Karnofsky performance scale \>60 for GBM patients.
5. 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.
6. Patients must have life expectancy \>3 months.
7. 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).

Bone Marrow Function:
* ANC ≥1500/μL.
* Hemoglobin ≥8 g/dL (The use of transfusion or other intervention to achieve hemoglobin ≥8 g/dL is acceptable. For those patients undergoing RBC transfusion, hemoglobin must be evaluated at least 14 days after the last RBC transfusion).
* Platelet count ≥100,000/μL (assessed ≥7 days following last platelet transfusion in patients with thrombocytopenia requiring platelets).

Blood clotting function:

\- INR and aPTT ≤1.5 x ULN. Study patients on therapeutic doses of anticoagulation medication must have INR and/or aPTT ≤ the upper limit of the therapeutic range for intended use.
8. Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test within 3 days of first dose of LP-184. A woman is of child-bearing potential unless she:

* has had a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy;
* is age ≥60 years and is amenorrhoeic; or
* is age \<60 years and has been amenorrhoeic for ≥12 months (including no irregular menses or spotting) in the absence of any medication which induces a menopausal state and has documented ovarian failure by serum estradiol and follicle-stimulating hormone levels within the institutional laboratory postmenopausal range).
9. WOCBP or must agree to use highly effective contraceptive methods and avoid egg donation during the study treatment and for 6 months after the last dose of LP-184.
10. Men of reproductive potential agree to use highly effective contraceptive methods and avoid sperm donation during the study treatment and for 3 months after the last dose of LP-184. A man is of child-producing potential unless he has had a bilateral vasectomy with documented aspermia or a bilateral orchiectomy.
11. Is willing to provide archived samples (blocks and/or slides) for comprehensive DDR genomic analyses and/or PTGR1 expression profiling and/or other genomic alterations if the patient has a PR/CR.
12. Regarding brain metastases, based on screening contrast brain MRI, patients must have 1of the following:

* No evidence of brain metastases
* Untreated brain metastases not requiring 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 that are either stable for at least 4 weeks since last treatment or progressed since prior local CNS therapy and not requiring immediate re-treatment with local therapy in the opinion of the investigator.


• Known or suspected leptomeningeal disease as documented by the investigator.
13. Male patients with partners currently pregnant, or male patients able to father children, and female patients of childbearing potential who are unwilling or unable to use highly effective methods of contraception as outlined in this protocol for the duration of the study and for at least 3 months (male) or 6 months (female) after last dose of study drug

Exclusion Criteria

1. 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.

Note: Low dose steroids (oral prednisone or equivalent ≤20 mg/day, except patients with GBM), localized non-CNS radiotherapy, previous hormonal therapy with luteinizing hormone-releasing hormone agonists for prostate cancer and treatment with bisphosphonates and RANKL inhibitors are not criteria for exclusion if such therapy has not been changed within 4 weeks before LP-184 treatment.
2. Any history of retinopathy and/or macular degeneration (without specifications or grades).
3. 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.
4. 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.
5. 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).
6. Are pregnant or breastfeeding. (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).
7. 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.
8. 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).
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 at a dose \> 2 mg of dexamethasone or equivalent 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 4 weeks must have elapsed between the end of whole brain radiotherapy and study enrollment (1 week for stereotactic radiotherapy).
12. For patients with suspected or known 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. (Note: this is not applicable to patients with GBM).
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Lantern Pharma Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Reggie Ewesuedo, MD

Role: STUDY_DIRECTOR

Lantern Pharma Inc.

Locations

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Highlands Oncology Group

Springdale, Arkansas, United States

Site Status RECRUITING

Cancer and Blood Specialty Clinic

Los Alamitos, California, United States

Site Status RECRUITING

Northwest Oncology & Hematology

Rolling Meadows, Illinois, United States

Site Status RECRUITING

Indiana University Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, United States

Site Status RECRUITING

Norton Healthcare, Inc.

Louisville, Kentucky, United States

Site Status RECRUITING

John Hopkins - The Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, United States

Site Status RECRUITING

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

Site Status RECRUITING

UT Health Science Center San Antonio

San Antonio, Texas, United States

Site Status RECRUITING

START Mountain Region

West Valley City, Utah, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Lyza Trejo

Role: CONTACT

+1 972-277-1136

Facility Contacts

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Amie Winn

Role: primary

(479)502-9289

Trong Nguyen

Role: primary

5627350602

Stefi Guillen

Role: backup

Nowsheen Azeemuddin

Role: primary

(847)577-0620

Cassandra Brass

Role: primary

Michael Buchanan

Role: primary

(502)629-2500 ext. 19472

Danielle Wendler

Role: primary

Ikenna Opurum

Role: primary

267-418-6160

Jasmine Deblanc

Role: primary

Casey Larsen

Role: primary

801-907-4752

Other Identifiers

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LTRN184-1AST23-1

Identifier Type: -

Identifier Source: org_study_id

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