PhI to Solid Tumors and PhII to Locally Advanced or mTNBC

NCT05390710 | Completed Phase 1 DMC

• 1 other identifier: LAE203CN2101
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 5

Brief Summary

PhI Dose Escalation with BOIN design in advanced Solid Tumor with Triple combination therapy to determine MTD and RP2D

Conditions

Solid Tumor; TNBC - Triple-Negative Breast Cancer

Keywords

TNBC

Outcome Measures

Primary Outcomes (4)

• To evaluate the safety.

  Frequency and severity of AEs (including incidence rate of DLTs).

  1year

• recommended Phase II dose (RP2D) of LAE005 and afuresertib and nab-paclitaxel as a combination treatment in patients with advanced solid tumours (including mTNBC)

  Frequency and severity of AEs (including incidence rate of DLTs).

  1year

• To evaluate the tolerability.

  Frequency and severity of AEs (including incidence rate of DLTs).

  1year

• To determine the maximum tolerated dose (MTD)

  Frequency and severity of AEs (including incidence rate of DLTs).

  1year

Secondary Outcomes (8)

• To assess the preliminary anti-tumor activity of LAE005 and afuresertib and nab-paclitaxel via DCR

  1 year

• To characterize the AUC0-t of LAE005 and afuresertib in patients receiving combination treatment of LAE005 and afuresertib and nab-paclitaxel.

  1 year

• To characterize the AUC0-inf of LAE005 and afuresertib in patients receiving combination treatment of LAE005 and afuresertib and nab-paclitaxel.

  1 year

• To characterize the Tmax of LAE005 and afuresertib in patients receiving combination treatment of LAE005 and afuresertib and nab-paclitaxel.

  1 year

• To characterize the T1/2 of LAE005 and afuresertib in patients receiving combination treatment of LAE005 and afuresertib and nab-paclitaxel.

  1 year

Study Arms (1)

Triple combination

EXPERIMENTAL

LAE005+Afuresertib+Nab-Paclitaxel

Combination Product: LAE005 + Afuresertib + Nab-Paclitaxel

Interventions

LAE005 + Afuresertib + Nab-Paclitaxel COMBINATION_PRODUCT

LAE005: 1200 mg IV Q3W, Afuresertib: 125 mg QD, Nab paclitaxel:125 mg/m D1, D8 Q3W

Triple combination

Eligibility Criteria

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

You may qualify if:

• Be ≥18 years of age on the day of signing the informed consent and be able to provide written informed consent for the trial.
• In Phase I, patients with histologically or cytologically confirmed advanced solid tumors are allowed to be enrolled in this study. mTNBC is a preferred cancer type to be enrolled although all solid tumors are qualified in phase I.
• In Phase I, patients with advanced solid tumors who have progressed after 0 to 3 lines of available standard of care (i.e. targeted therapy, immunotherapy and/or chemotherapy) are allowed to be enrolled in this study. If anti-cancer drugs have been used, the washout period is 4 weeks or 5 half-lives (whichever is longer).
• In phase I, there is no biomarker test required.
• Have measurable disease per RECIST 1.1 as assessed by local image study, that has not undergone radiotherapy.
• Patients must have an Eastern Cooperative Oncology Group (ECOG) Performance Score of 0 or 1 in both Phase I and II.
• Have adequate organ function as defined below. If the specimens are collected within 10 days prior to the start of study treatment, the same tests in Day 1 can be waived to avoid redundancy.
• Hematological:
• Absolute neutrophil count (ANC) ≥1500/μL
• Platelets within the normal range in phase I, and platelet count ≥100,000/µl in phase II
• Hemoglobin ≥9.0 g/dL or ≥5.6 mmol/L
• Criteria must be met without erythropoietin dependency and without packed red blood cell (rRBC) transfusion within last 2 weeks.
• Renal
• Creatinine ≤1.5 × ULN OR
• Measured or calculated per institutional standard creatinine clearance (GFR can also be used in place of creatinine or creatinine clearance) ≥30 mL/min for participant with creatinine levels \>1.5 × institutional ULN.

You may not qualify if:

• A woman of child-bearing potential (WOCBP), who has a positive urine pregnancy test (e.g. within 72 hours) prior to treatment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed.
• Has a history of autoimmune diseases or diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study drug.
• Has a recent major surgery requiring hospitalization (\<3 months from randomization) or use of IV antibiotics for systemic infection (\< 2 months from randomization).
• Has a known additional malignancy that is progressing or has required active treatment within the past 3 years (Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, that have undergone potentially curative therapy are not excluded).
• History of seizure of condition that may predispose to seizure that needs anti-epileptic medications; brain arteriovenous malformation; or intracranial masses, such as schwannomas and meningiomas that are causing edema or mass effect.
• Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e., without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment.
• Has severe hypersensitivity (≥Grade 3) to LAE005 or afuresertib and/or any of their excipients.
• Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.
• Has a history of (non-infectious) pneumonitis that required steroids or has concurrent pneumonitis.
• New York Heart Association congestive heart failure of grade II or above, unstable angina, myocardial infarction within the past 6 months or serious cardiac arrhythmia associated with significant cardiovascular impairment within the past 6 months.
• Prolongation of corrected QTc interval, as corrected by the Frederica's correction formula to ≥450 msec for males and ≥470 msec for females; unless prolonged QTc interval due to right bundle branch block or left bundle branch block with a pacemaker.
• Presence of uncontrolled hypertension (systolic blood pressure \>160 mmHg or diastolic BP\>100 mmHg). Patients with a history of hypertension are allowed, provided that BP is controlled to within these limits by anti-hypertensive treatment.
• Has a known history of Hepatitis B (defined as HBsAg reactive) or known active Hepatitis C virus (defined as HCV RNA \[qualitative\] is detected) and HIV infection.
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator.

Sponsors & Collaborators

• Laekna Limited: lead

Study Sites (5)

The first affiliated hopsital of bengbu medical college

Bengbu, Anhui, China

Location

Cancer Hospital Chinese Academy of Medical Sciences

Beijing, Beijing Municipality, China

Location

Sun Yat-sen Memorial Hospital

Guangzhou, China

Location

Sir RunRun Shaw Hospital Zhejiang University School of Medicine

Hangzhou, China

Location

Tianjin Medical University Cancer Institute & Hospital

Tianjin, China

Location

MeSH Terms

Conditions

Triple Negative Breast Neoplasms

Interventions

afuresertib; 130-nm albumin-bound paclitaxel

Condition Hierarchy (Ancestors)

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Binghe NA Xu

  Cancer Institute and Hospital, Chinese Academy of Medical Sciences

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Masking Details: Open Label for phase I
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: BOIN for Phase I with 1 treatment arm

Study Record Dates

• First Submitted: July 26, 2021
• First Posted: May 25, 2022
• Study Start: June 12, 2021
• Primary Completion: December 11, 2023
• Study Completion: December 11, 2023
• Last Updated: October 10, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

CN (5)