A Study of LAE118 as Monotherapy and in Combination With Antitumor Agents in Advanced Solid Tumors

NCT07787520 | Not Yet Recruiting Phase 1

• 1 other identifier: LAE118CN1002
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 6

Brief Summary

Study Title: A Phase I, Open-Label, Dose-Escalation and Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of LAE118 as Monotherapy and in Combination With Other Antitumor Agents in Patients With Advanced Solid Tumors Study Design Overview: This is an open-label, multicenter Phase I clinical trial comprising three cohorts: Cohort A (LAE118 monotherapy), Cohort B (LAE118 plus fulvestrant), and Cohort C (LAE118 plus fulvestrant and palbociclib). Each cohort consists of two stages. Stage I evaluates safety and determines the maximum tolerated dose (MTD) and recommended dose (RD) of LAE118; Stage II assesses the preliminary efficacy of LAE118 at the RD.

Conditions

Patients With Advanced Solid Tumors

Outcome Measures

Primary Outcomes (25)

• Number of participants with adverse events (AEs)

  Frequency and severity of AEs, including treatment-related AEs, serious AEs (SAEs), and AEs leading to treatment discontinuation, as assessed by CTCAE v5.0.

  From ICF signing to 30 days after last dose, up to ~24 months

• Number of participants with dose-limiting toxicities (DLTs)

  Per protocol definition. DLT observation period: C0D1-C1D28 for Cohort A; C1D1-C1D28 for Cohorts B and C.

  35 days (Cohort A) / 28 days (Cohorts B and C)

• Change from baseline in QTcF interval as assessed by 12-lead ECG

  Triplicate recordings within 10 min, ≥1 min apart. Fridericia's correction。 Unit: msec

  Baseline to EOT, up to ~24 months

• Change from baseline in PR interval as assessed by 12-lead ECG

  Unit: bpm

  Baseline to EOT, up to ~24 months

• Change from baseline in QRS duration as assessed by 12-lead ECG

  Unit: msec

  Baseline to EOT, up to ~24 months

• Change from baseline in heart rate as assessed by 12-lead ECG

  Unit: bpm

  Baseline to EOT, up to ~24 months

• Change from baseline in systolic and diastolic blood pressure

  Unit: mmHg

  Baseline to EOT, up to ~24 months

• Change from baseline in pulse rate

  Unit: bpm

  Baseline to EOT, up to ~24 months

• Change from baseline in respiratory rate

  Unit: breaths/min

  Baseline to EOT, up to ~24 months

• Change from baseline in body temperature

  Unit: °C

  Baseline to EOT, up to ~24 months

• Change from baseline in physical examination findings

  Full-body exam at screening and EOT; targeted exam (head/neck, cardiovascular, respiratory, abdominal, musculoskeletal, neurological, skin) at other visits. Presence of clinically significant abnormalities.

  Baseline to EOT, up to ~24 months

• Change from baseline in hematology parameters

  WBC with differential (10⁹/L), RBC (10¹²/L), hemoglobin (g/L), hematocrit (%), platelet count (10⁹/L).

  Baseline to EOT, up to ~24 months

• Change from baseline in serum chemistry - enzymes

  ALT, AST, ALP, GGT, LDH, CK, CK-MB, amylase, lipase. Unit: U/L

  Baseline to EOT, up to ~24 months

• Change from baseline in serum chemistry - bilirubin, creatinine, and bile acids

  Total bilirubin, direct bilirubin, creatinine, bile acids. Unit: μmol/L

  Baseline to EOT, up to ~24 months

• Change from baseline in serum chemistry - electrolytes and metabolites

  Sodium, potassium, calcium, magnesium, phosphorus, BUN/urea, total cholesterol, HDL-C, LDL-C, triglycerides. Unit: mmol/L

  Baseline to EOT, up to ~24 months

• Change from baseline in serum albumin and total protein

  Unit: g/L

  Baseline to EOT, up to ~24 months

• Change from baseline in prothrombin time (PT) and activated partial thromboplastin time (aPTT)

  Unit: seconds

  Baseline to EOT, up to ~24 months

• Change from baseline in international normalized ratio (INR)

  Baseline to EOT, up to ~24 months

• Change from baseline in fibrinogen

  Unit: g/L

  Baseline to EOT, up to ~24 months

• Change from baseline in thyroid-stimulating hormone (TSH)

  mIU/L

  Baseline to EOT, up to ~24 months

• Change from baseline in free triiodothyronine (FT3) and free thyroxine (FT4)

  Unit: pmol/L

  Baseline to EOT, up to ~24 months

• Change from baseline in adrenal function parameters

  Cortisol, ACTH, aldosterone, renin, and aldosterone/renin ratio.

  Baseline to EOT, up to ~24 months

• Change from baseline in troponin I/T

  Unit: ng/mL

  Baseline to EOT, up to ~24 months

• Change from baseline in brain natriuretic peptide (BNP)

  Unit: pg/mL

  Baseline to EOT, up to ~24 months

• Change from baseline in urinalysis parameters

  Urine protein, glucose, ketones, occult blood, and specific gravity.

  Baseline to EOT, up to ~24 months

Secondary Outcomes (20)

• Objective response rate (ORR)

  Every 8 weeks from C1D1 to progression/EOT, up to ~24 months

• Clinical benefit rate (CBR)

  Every 8 weeks from C1D1, up to ~24 months

• Duration of response (DOR)

  From first response to progression/death, up to ~24 months

• Progression-free survival (PFS)

  C1D1 to progression/death, up to ~24 months

• Peak plasma concentration (Cmax) of LAE118

  Day 1 and Day 15: pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-dose.

Study Arms (3)

Cohort A (LAE118 monotherapy)

EXPERIMENTAL

Drug: LAE118

Cohort B (LAE118 plus fulvestrant)

EXPERIMENTAL

Drug: LAE118; Drug: Fulvestrant

Cohort C (LAE118 plus fulvestrant and palbociclib)

EXPERIMENTAL

Drug: LAE118; Drug: Fulvestrant; Drug: Palbociclib

Interventions

LAE118 DRUG

LAЕ118 is a novel, allosteric and highly potent selective inhibitor of PIK3CA. Its activity against PIK3CA mutant cells is superior to that of other broad-spectrum selective inhibitors.

Cohort A (LAE118 monotherapy); Cohort B (LAE118 plus fulvestrant); Cohort C (LAE118 plus fulvestrant and palbociclib)

Fulvestrant DRUG

Fulvestrant is approved for the treatment of post-menopausal metastatic breast cancer following disease progression on therapy with an anti-estrogen therapy.

Cohort B (LAE118 plus fulvestrant); Cohort C (LAE118 plus fulvestrant and palbociclib)

Palbociclib DRUG

Palbociclib is a CDK4/6 inhibitor. Multiple clinical studies have shown that palbociclib combined with endocrine therapy has demonstrated significant clinical benefits in study participants with HR+/HER2- advanced breast cancer.

Cohort C (LAE118 plus fulvestrant and palbociclib)

Eligibility Criteria

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

You may qualify if:

• Age ≥18 years at the time of signing the informed consent form.
• Ability to provide written informed consent to participate in this study.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• During the screening period, a blood sample must be provided for PIK3CA testing at the central laboratory. Only participants with confirmed positive PIK3CA mutation results are eligible for enrollment. Participants with previously documented positive PIK3CA mutation results from local laboratory testing may be enrolled; however, a blood sample must still be collected during the screening period for central laboratory confirmation.
• At least one measurable lesion as defined by RECIST version 1.1 criteria.
• Histologically or cytologically confirmed locally advanced (unresectable) or metastatic solid tumor, meeting the specific criteria for each cohort:
• Cohort A (Stage I, Dose Escalation): Histologically or cytologically confirmed locally advanced (unresectable) or metastatic solid tumor. Lymphoma is excluded.
• Cohort A (Stage II): Histologically or cytologically confirmed locally advanced (unresectable) or metastatic head and neck squamous cell carcinoma (HNSCC) or gynecologic cancers (ovarian, cervical, or endometrial cancer).
• Cohort A (Stage I, Backfill Enrollment) and Cohorts B/C: Histologically or cytologically confirmed locally advanced (unresectable) or metastatic HR+/HER2- breast cancer, based on the most recent tumor specimen.
• HR+/HER2- breast cancer is defined as HER2-negative and ER-positive, regardless of PR expression status.
• Estrogen receptor (ER) positive: Defined as ≥1% of tumor cells demonstrating ER positivity by immunohistochemistry (IHC).
• Progesterone receptor (PR) positive: Defined as ≥1% of tumor cells demonstrating PR positivity by IHC.
• HER2-negative: Defined as IHC intensity of 0 or 1+, or IHC intensity of 2+ without evidence of amplification by in situ hybridization (ISH), or absence of IHC testing and no evidence of amplification by ISH (based on the 2023 updated ASCO-CAP guidelines).
• Prior antitumor therapy:
• Cohort A: Disease progression after adequate standard therapy, or no effective standard therapy available.

You may not qualify if:

• Prior treatment with a PI3K, AKT, or mTOR inhibitor without clinical benefit ("benefit" defined as achieving a best overall response \[BOR\] of CR/PR/SD during PI3K, AKT, or mTOR inhibitor therapy), except for participants who discontinued treatment due to documented intolerance.
• Cohort C only: Participants with prior palbociclib exposure are not eligible for enrollment.
• Participants with type 1 diabetes mellitus or type 2 diabetes mellitus requiring antidiabetic medication are not eligible for enrollment.
• Participants with metaplastic breast cancer or inflammatory breast cancer.
• Known active, uncontrolled, or symptomatic central nervous system (CNS) metastases or leptomeningeal carcinomatosis. Participants with previously treated CNS metastases may be enrolled if all of the following criteria are met:
• At least one measurable non-CNS lesion per RECIST version 1.1 criteria. No history of intracranial or spinal cord hemorrhage. Radiographic stability: No evidence of progression on imaging following completion of CNS-directed therapy. The interval between post-treatment imaging and screening imaging must be at least 4 weeks, with no evidence of progression.
• Clinical stability: No requirement for corticosteroids, diuretics, mannitol, or other agents to reduce intracranial pressure, and no requirement for antiepileptic drugs for at least 14 days prior to the planned start date of study treatment.
• Uncontrolled pleural effusion or ascites (requiring drainage every 2 weeks or more frequently, or requiring an indwelling pleural or peritoneal catheter).
• Concurrent malignancy or history of another malignancy within 3 years prior to the planned start date of study treatment, except for adequately treated basal cell carcinoma, squamous cell carcinoma of the skin, non-melanoma skin cancer, or cervical carcinoma in situ treated with curative intent.
• Major surgery or significant trauma within 28 days prior to initiation of study treatment, or anticipated need for major surgery during the study treatment period. Participants must have fully recovered from prior surgery, including adequate wound healing.
• Receipt of intravenous antibiotics for infection within 2 weeks prior to the planned start date of study treatment.
• History of seizures or predisposing factors for seizures; cerebral arteriovenous malformation; or intracranial space-occupying lesions causing edema or clinical symptoms.
• Meeting any of the following criteria within 26 weeks prior to the planned start date of study treatment:
• History of angina pectoris, coronary artery bypass grafting, symptomatic pericarditis, or myocardial infarction within 12 months prior to initiation of study treatment.
• Documented history of congestive heart failure (New York Heart Association \[NYHA\] Class III-IV).

Sponsors & Collaborators

• Laekna Limited: lead

Study Sites (6)

Anhui Provincial Cancer Hospital

Hefei, Anhui, 233004, China

Location

Cancer Hospital, Chinese Academy of Medical Sciences

Beijing, Beijing Municipality, 100021, China

Location

The First Hospital of Jilin University

Changchun, Jilin, 130021, China

Location

Zhongshan Hospital Affiliated to Fudan University

Shanghai, Shanghai Municipality, 200032, China

Location

Shanghai East Hospital

Shanghai, Shanghai Municipality, 200123, China

Location

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, 310022, China

Location

MeSH Terms

Interventions

Fulvestrant; palbociclib

Intervention Hierarchy (Ancestors)

Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Central Study Contacts

Zheng Zhang

CONTACT

+8617602165910; zheng.zhang@laekna.com

Study Design

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

Study Record Dates

• First Submitted: July 26, 2026
• First Posted: August 26, 2026
• Study Start: August 1, 2026
• Primary Completion (Estimated): March 1, 2029
• Study Completion (Estimated): December 1, 2029
• Last Updated: August 26, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (6)