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CompletedNCT04097756Updated May 1, 2023

A Phase I Study of LX-039 Tablets

A Phase 1 interventional study of LX-039 tablets in Advanced Breast Cancer, sponsored by Shandong Luoxin Pharmaceutical Group Stock Co., Ltd.. Completed at 1 site in China. Open to female participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2023-05-01.

Sponsored by Shandong Luoxin Pharmaceutical Group Stock Co., Ltd. · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
44
Allocation
Non-randomized
Ages
18 Years to 75 Years
Sex
Female
01

Study 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.

02

Conditions studied

  • Advanced Breast Cancer

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03

Who can participate

Ages eligible
18 Years to 75 Years
Sexes eligible
Female
Accepts healthy volunteers
No

Inclusion criteria

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

Exclusion criteria

Exclusion Criteria:

  1. Subjects with HER2-overexpressing breast cancer.
  2. Subjects with known brain metastases or other central nervous system metastases that are symptomatic or untreated.
  3. Patients with symptomatic advanced disease who have spread to the viscera and are at risk of life-threatening complications.
  4. Subjects who received second-line or above chemotherapy.
  5. Subjects with known allergy to this product or any of its components.
  6. Subjects who previously used other estrogen receptor down regulators than fulvestrant.
  7. Subjects who received endocrine therapy or other anti-tumor agent or radiotherapy within 4 weeks prior to study entry.
  8. Subjects who received cell therapy or tumor vaccine therapy;
  9. Subjects with severe immunosuppression .
  10. Severe or uncontrolled disease.
  11. Subjects with diseases or abnormalities that may affect the administration and absorption of drugs.
  12. Subjects with other malignancy within 5 years prior to study entry.
  13. Subjects with other high risks of thrombosis or require long-term use of antiplatelet drugs.
  14. Subjects with history of definite neurological or psychiatric disorders in the past.
  15. Subjects who are HIV(human immunodeficiency virus) antibody positive, HBsAg(hepatitis B surface antigen) positive or HCV(hepatitis C virus)antibody positive.
  16. Subjects with other uncontrolled malignant/non-malignant diseases, significant laboratory abnormalities, participation in the study may increase the risk.
04

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Single group
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
44 participants (actual)

Study arms

  • Experimental
    Part1：dose escalation

    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

  • Experimental
    Part 2：dose expansion

    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

  • DrugLX-039 tablets

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

05

What researchers measure

Primary outcomes

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

    Incidence of dose limiting toxicities (DLTs)

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

Secondary outcomes

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

    Number of participants with treatment related. adverse events as assessed by CTCAE v5.0

    Time frame: through study completion,an average of 1 year

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

    Objective response rate (ORR)

    Time frame: through study completion，an average of 1 year.

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

    proportion of subjects with complete response (CR）

    Time frame: through study completion，an average of 1 year.

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

    proportion of subjects with partial response (PR）

    Time frame: through study completion，an average of 1 year.

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

    proportion of subjects with stable disease (SD)

    Time frame: through study completion，an average of 1 year.

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

    proportion of subjects with progressive disease (PD)

    Time frame: through study completion，an average of 1 year.

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

    duration of response (DoR)

    Time frame: through study completion，an average of 1 year.

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

    disease control rate (DCR)

    Time frame: through study completion，an average of 1 year.

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

    clinical benefit rate (CBR)

    Time frame: through study completion，an average of 1 year.

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

    time to progression (TTP)

    Time frame: through study completion，an average of 1 year.

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

    progression-free survival (PFS)

    Time frame: through study completion，an average of 1 year.

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

    overall survival (OS)

    Time frame: through study completion，an average of 1 year.

  13. Comparison of changes in maximum uptake ability of FES(progression free survival) in breast cancer lesions before and after treatment with LX-039 by PET(positron emission tomography) scan (performed in some subjects)

    Decrease in SUVmax in comparison with that before treatment

    Time frame: Up to the third day of Cycle 2(each cycle is 28 days)

  14. PK profiles after a single dose of LX-039

    Peak Concentration (Cmax)

    Time frame: Up to the third day of Cycle 0(Cycle 0 is 7 days)

  15. PK profiles after a single dose of LX-039

    Peak Time (Tmax)

    Time frame: Up to the third day of Cycle 0(Cycle 0 is 7 days)

  16. PK profiles after a single dose of LX-039

    Elimination Half-life (t1/2)

    Time frame: Up to the third day of Cycle 0(Cycle 0 is 7 days)

  17. PK profiles after a single dose of LX-039

    Eliminate Rate Constant (Kel)

    Time frame: Up to the third day of Cycle 0(Cycle 0 is 7 days)

  18. PK profiles after a single dose of LX-039

    Mean Residence Time (MRT)

    Time frame: Up to the third day of Cycle 0(Cycle 0 is 7 days)

  19. PK profiles after a single dose of LX-039

    Area under plasma Concentration-time curve from 0 time to 24 hours (AUC0-24h)

    Time frame: Up to the third day of Cycle 0(Cycle 0 is 7 days)

  20. PK profiles after a single dose of LX-039

    Area under plasma Concentration-time curve from 0 time to sampling time t of the last measurable concentration (AUC0-last)

    Time frame: Up to the third day of Cycle 0(Cycle 0 is 7 days)

  21. PK profiles after a single dose of LX-039

    Area under plasma Concentration-time curve from administration (0) to infinity (AUC0-inf)

    Time frame: Up to the third day of Cycle 0(Cycle 0 is 7 days)

  22. PK profiles after a single dose of LX-039

    Apparent Total Clearance (CL/F)

    Time frame: Up to the third day of Cycle 0(Cycle 0 is 7 days)

  23. PK profiles after a single dose of LX-039

    Apparent Volume of Distribution (Vd/F)

    Time frame: Up to the third day of Cycle 0(Cycle 0 is 7 days)

  24. PK profiles after continuous administration of LX-039

    Trough Concentration at Steady State (Css, min)

    Time frame: Up to the Second day of Cycle 2(each cycle is 28 days)

  25. PK profiles after continuous administration of LX-039

    Peak Concentration at Steady State (Css, max)

    Time frame: Up to the Second day of Cycle 2(each cycle is 28 days)

  26. PK profiles after continuous administration of LX-039

    Average Concentration at Steady State (Css, av)

    Time frame: Up to the Second day of Cycle 2(each cycle is 28 days)

  27. PK profiles after continuous administration of LX-039

    Peak Time (Tss, max)

    Time frame: Up to the Second day of Cycle 2(each cycle is 28 days)

  28. PK profiles after continuous administration of LX-039

    Apparent Volume of Distribution at steady state (Vss/F)

    Time frame: Up to the Second day of Cycle 2(each cycle is 28 days)

  29. PK profiles after continuous administration of LX-039

    Steady-state Clearance Half-life (tss,1/2)

    Time frame: Up to the Second day of Cycle 2(each cycle is 28 days)

  30. PK profiles after continuous administration of LX-039

    Total Body Clearance (CLss/F)

    Time frame: Up to the Second day of Cycle 2(each cycle is 28 days)

  31. PK profiles after continuous administration of LX-039

    Coefficient of Fluctuation (DF)

    Time frame: Up to the Second day of Cycle 2(each cycle is 28 days)

  32. PK profiles after continuous administration of LX-039

    Area under Plasma Concentration-time Curve at Steady State (AUCss)

    Time frame: Up to the Second day of Cycle 2(each cycle is 28 days)

  33. PK profiles after continuous administration of LX-039

    Accumulation Coefficient (Rac)

    Time frame: Up to the Second day of Cycle 2(each cycle is 28 days)

06

Study locations

1 site
  • Fudan University Shanghai Cancer Center
    Shanghai, Shanghai 200032, China
07

References and documents

Publications

  • 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. PubMed 35436589 ↗
08

Registry details

Key details

Study ID
NCT04097756
Lead sponsor
Shandong Luoxin Pharmaceutical Group Stock Co., Ltd.
Responsible party
Sponsor
First posted
Sep 20, 2019
Start date
Jan 7, 2020
Primary completion
Aug 8, 2022
Completion
Feb 7, 2023
Last update
May 1, 2023

Oversight

FDA-regulated drug
No
FDA-regulated device
No
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