A Phase I Study of LX-039 Tablets

NCT04097756 | Completed Phase 1

• 1 other identifier: OE861801
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase I dose escalation and expansion study in patients with ER+, HER2- advanced breast cancer to explore the tolerance, PK/PD(pharmacokinetics/pharmacodynamics) profiles and preliminary anti-tumor activity of different doses of LX-039 tablets. The trial consists of two parts, dose escalation and dose expansion. Part 1 is the dose escalation phase with initial 6 dose groups, and "3 + 3" design is used to explore MTD of the drug; Part 2 is the dose expansion phase with 2 \~ 3 doses selected for expansion according to the escalation results of Part 1, and more subjects are enrolled to further observe the tolerance and preliminary anti-tumor activity of the drug. After the completion of dose expansion, the recommended phase II dose (RP2D) will be determined after discussion based on the obtained tolerance and PK/PD data.

Conditions

Advanced Breast Cancer

Outcome Measures

Primary Outcomes (1)

• To explore the tolerance of LX-039 in ER +, HER2 - patients with advanced breast cancer

  Incidence of dose limiting toxicities (DLTs)

  DLT observation period(5 weeks for dose escalation, 4 weeks for dose expansion)

Secondary Outcomes (33)

• The safety of LX-039 in ER +, HER2 - patients with advanced breast cancer

  through study completion,an average of 1 year

• To explore the efficacy of LX-039 in ER +, HER2 - patients with advanced breast cancer according to Recist 1.1.

  through study completion，an average of 1 year.

• To explore the efficacy of LX-039 in ER +, HER2 - patients with advanced breast cancer according to Recist 1.1.

  through study completion，an average of 1 year.

• To explore the efficacy of LX-039 in ER +, HER2 - patients with advanced breast cancer according to Recist 1.1.

  through study completion，an average of 1 year.

• To explore the efficacy of LX-039 in ER +, HER2 - patients with advanced breast cancer according to Recist 1.1.

  through study completion，an average of 1 year.

Study Arms (2)

Part1：dose escalation

EXPERIMENTAL

The investigational product for this study is LX-039 tablets,which can be administered orally. 6\~8 ascending dose level until MTD and the specification included 50 mg, 100 mg, 200 mg, 400 mg, 600 mg , 800 mg,1050 mg and 1400 mg. LX-039 tablets will be administered in a therapeutic cycle of 28 days once a day orally. The subjects will continue therapy with LX-039 if good safety and tolerability were assessed by investigators after one cycle treatment. The treatment will continue until disease progression, unacceptable toxicity, withdrawal of consent, or study termination.

Drug: LX-039 tablets

Part 2：dose expansion

EXPERIMENTAL

2\~3 selected tolerable dose will be selected according to the tolerance and FES PET results of dose escalation phase.The subjects will continue therapy with LX-039 if good safety and tolerability were assessed by investigators after one cycle treatment. The treatment will continue until disease progression, unacceptable toxicity, withdrawal of consent, or study termination.

Drug: LX-039 tablets

Interventions

LX-039 tablets DRUG

orally once daily until disease progression, unacceptable toxicity, withdrawal of consent, or study termination

Part 2：dose expansion; Part1：dose escalation

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Be able to read and sign the informed consent form.
• Adult females (aged ≥18 and ≤75 years).
• Be diagnosed with breast cancer confirmed by pathological examination.
• Be histologically or cytologically confirmed estrogen receptor positive (ER+≥1% positive staining).
• Be postmenopausal.
• Subjects who have previously received endocrine therapy and obtained benefit.
• ECOG(Eastern Cooperative Oncology Group) score ≤ 1.
• Subjects in part2 of the study need to have measurable lesions that meet RECIST 1.1 criteria.
• Has recovered from toxicity or injury from prior chemotherapy/radiotherapy .
• Enough hematology and organ function.
• Expected survival\>3 months.

You may not qualify if:

• Subjects with HER2-overexpressing breast cancer.
• Subjects with known brain metastases or other central nervous system metastases that are symptomatic or untreated.
• Patients with symptomatic advanced disease who have spread to the viscera and are at risk of life-threatening complications.
• Subjects who received second-line or above chemotherapy.
• Subjects with known allergy to this product or any of its components.
• Subjects who previously used other estrogen receptor down regulators than fulvestrant.
• Subjects who received endocrine therapy or other anti-tumor agent or radiotherapy within 4 weeks prior to study entry.
• Subjects who received cell therapy or tumor vaccine therapy;
• Subjects with severe immunosuppression .
• Severe or uncontrolled disease.
• Subjects with diseases or abnormalities that may affect the administration and absorption of drugs.
• Subjects with other malignancy within 5 years prior to study entry.
• Subjects with other high risks of thrombosis or require long-term use of antiplatelet drugs.
• Subjects with history of definite neurological or psychiatric disorders in the past.
• Subjects who are HIV(human immunodeficiency virus) antibody positive, HBsAg(hepatitis B surface antigen) positive or HCV(hepatitis C virus)antibody positive.

Sponsors & Collaborators

• Shandong Luoxin Pharmaceutical Group Stock Co., Ltd.: lead

Study Sites (1)

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, 200032, China

Location

Related Publications (1)

• Lu J, Chan CC, Sun D, Hu G, He H, Li J, Dong J, Liu K, Shen L, Hu L, Gu Q, Chen S, Wang T, Gong T, Tang W, Li X, Zhu X, Zeng X, Zhu Y, Xia Y, Huang Y, Zhu Y, Liu Z, Ding CZ. Discovery and preclinical profile of LX-039, a novel indole-based oral selective estrogen receptor degrader (SERD). Bioorg Med Chem Lett. 2022 Jun 15;66:128734. doi: 10.1016/j.bmcl.2022.128734. Epub 2022 Apr 15.

  PMID: 35436589 DERIVED

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 29, 2019
• First Posted: September 20, 2019
• Study Start: January 7, 2020
• Primary Completion: August 8, 2022
• Study Completion: February 7, 2023
• Last Updated: May 1, 2023

Record last verified: 2020-10

Locations

CN (1)