Patients With Advanced Solid TumorsPhase 1NCT07787520
A Study of LAE118 as Monotherapy and in Combination With Antitumor Agents in Advanced Solid Tumors
A Phase 1 study testing LAE118, Fulvestrant and Palbociclib in people with Patients With Advanced Solid Tumors, run by Laekna Limited at 6 sites in China.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Patients With Advanced Solid Tumors
- What is being tested?
- LAE118, Fulvestrant and Palbociclib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 150 participants
- Where
- 6 sitesChina
- Study dates
- Aug 2026to Dec 2029
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
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- 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.
- Cohorts B/C:
- Receipt of no more than 3 lines of systemic antitumor therapy in the advanced setting (including at least 1 line of endocrine therapy, no more than 1 line of CDK4/6 inhibitor therapy, and no more than 1 line of chemotherapy).
- If disease recurrence occurs during adjuvant endocrine therapy or within 12 months of completion of adjuvant endocrine therapy, such adjuvant therapy will be counted as one line of prior therapy.
- Prior fulvestrant therapy is permitted; however, the proportion of participants with prior fulvestrant exposure must not exceed 50% of the total enrolled participants in Cohort B and Cohort C, respectively.
- Female participants with HR+/HER2- advanced breast cancer who are postmenopausal, premenopausal, or perimenopausal are eligible for enrollment. In Cohorts B/C, male participants and female participants with HR+/HER2- advanced breast cancer who are premenopausal or perimenopausal must receive continuous ovarian function suppression throughout the study period (initiation of luteinizing hormone-releasing hormone agonist [LHRHa] no later than Day 1 of Cycle 1).
- Menopause is defined as follows [34]:
- Prior bilateral oophorectomy. Age ≥60 years. Age <60 years with amenorrhea for ≥12 months in the absence of prior chemotherapy, tamoxifen, toremifene, or ovarian suppression, and with estradiol and follicle-stimulating hormone (FSH) levels in the postmenopausal range.
- Age <60 years with chemotherapy-induced amenorrhea for ≥12 months and FSH and estradiol levels consistently in the postmenopausal range upon serial assessment.
- Age <60 years currently receiving tamoxifen with FSH and estradiol levels in the postmenopausal range.
- Participants in Cohorts B/C must have no contraindications to fulvestrant, including hypersensitivity to fulvestrant or any of its components, or hepatic impairment classified as Child-Pugh Class B or C. Participants in Cohort C must have no contraindications to palbociclib, including hypersensitivity to palbociclib or any of its components.
- Fasting plasma glucose <7.7 mmol/L and hemoglobin A1c (HbA1c) <7.0%.
- A minimum washout period of 4 weeks or 5 half-lives (whichever is shorter) between the end of the last antitumor therapy and the planned start date of study treatment.
- Completion of radiotherapy at least 4 weeks prior to the planned start date of study treatment; completion of palliative radiotherapy for bone or other metastatic lesions at least 2 weeks prior to the planned start date of study treatment.
- Ability to swallow and absorb oral medications, with no gastrointestinal disorders that would interfere with drug absorption.
- Resolution of toxicities related to prior antitumor therapy to Grade ≤1, except for stable residual symptoms (alopecia, peripheral sensory neuropathy, skin hyperpigmentation, dysgeusia).
- Female participants of childbearing potential must agree to use highly effective contraception from the time of enrollment until at least 1 year after the last dose of study treatment. Acceptable methods include:
- Complete abstinence (if this is their preferred and usual lifestyle). Intrauterine device (IUD) or hormonal intrauterine system. Contraceptive implant. Oral contraceptives (combined with barrier contraception). Partner has undergone vasectomy with confirmed azoospermia. Male participants with female partners of childbearing potential must agree to use effective contraception (e.g., condom use) from the time of enrollment until at least 1 year after the last dose of study treatment.
- Female participants of childbearing potential must have a negative serum pregnancy test during the screening period.
- Adequate organ function, defined as follows:
- Hematologic: The following criteria must be met without the use of erythropoietin, growth factors, or packed red blood cell transfusion within 14 days prior to screening laboratory assessments:
- Absolute neutrophil count (ANC) ≥1.5 × 10⁹/L. Platelet count ≥100 × 10⁹/L. Hemoglobin ≥10.0 g/dL.
- Hepatic:
- Total bilirubin ≤1.5 × upper limit of normal (ULN). Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × ULN (or ≤3 × ULN for participants with liver metastases).
- Serum albumin ≥30 g/L.
- Renal:
- Creatinine clearance ≥60 mL/min (calculated using the Cockcroft-Gault formula).
- Coagulation:
- International normalized ratio (INR) ≤1.5 × ULN. Activated partial thromboplastin time (aPTT) ≤1.5 × ULN. For participants requiring anticoagulation with warfarin, INR must be stably maintained within the range of 2 to 3. For participants with mechanical heart valves requiring anticoagulation, INR may be maintained within the range of 2.5 to 3.5.
- Adrenal function tests during screening show no clinically significant abnormalities.
- Bone mineral density testing (dual-energy X-ray absorptiometry [DEXA]) must be performed during the screening period, with a T-score >-2.5 (based on the lowest value across multiple sites assessed).
Who cannot join
- 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.
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- 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).
- Documented cardiomyopathy. Left ventricular ejection fraction (LVEF) <50% (if applicable). History of clinically significant arrhythmias (including but not limited to ventricular tachycardia, complete left bundle branch block, high-grade atrioventricular block, supraventricular tachycardia, or atrial fibrillation).
- Corrected QTcF interval >450 ms (corrected using Fridericia's formula), based on the mean of 3 consecutive electrocardiograms obtained within 10 minutes at intervals of at least 1 minute apart. Participants with a history of additional risk factors for torsades de pointes (TdP) (e.g., heart failure, hypokalemia, family history of long QT syndrome) are not eligible for enrollment.
- Suspected pneumonitis or interstitial lung disease (confirmed by imaging or CT scan), or history of pneumonitis or interstitial lung disease within the past 6 months.
- Electrolyte abnormalities requiring treatment.
- History of and/or current adrenal disorders (e.g., Cushing's disease, Addison's disease, adrenal insufficiency).
- Systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg; however, participants with hypertension controlled with oral antihypertensive medication (systolic BP <140 mmHg and diastolic BP <90 mmHg) are eligible for enrollment.
- Active HBV infection (defined as HBsAg positive with HBV DNA ≥200 IU/mL or ≥1000 copies/mL), active HCV infection (defined as anti-HCV antibody positive with detectable HCV RNA), or HIV infection (defined as anti-HIV antibody positive).
- Note: As outlined in the U.S. FDA guidance "Cancer Clinical Trial Eligibility Criteria: Patients with HIV, Hepatitis B Virus, or Hepatitis C Virus Infections," participants with well-controlled HIV, HBV, or HCV are eligible. Participants receiving effective antiviral therapy with controlled viral loads should continue the same regimen throughout the study treatment period.
- Known psychiatric illness or substance use disorder that would impair the ability to comply with study requirements.
- Known history of solid organ transplantation or hematopoietic stem cell transplantation.
- Receipt of a live vaccine or live attenuated vaccine within 30 days prior to the first dose of study treatment.
- Any known medical condition, concurrent therapy, or laboratory abnormality that, in the investigator's judgment, could confound study results, interfere with participant adherence to study procedures, or render participation inconsistent with the participant's best interest.
- Any concurrent ocular or intraocular disease (e.g., uveitis, vitritis) that, in the opinion of the investigator or ophthalmologist, requires medical or surgical intervention during the study to prevent or treat conditions that could lead to vision loss.
- Cataract of Grade ≥2 severity per CTCAE version 5.0.
- Use of moderate or strong CYP3A4 and/or CYP2C8 inhibitors and/or P-gp inhibitors within less than 5 elimination half-lives or 1 week (whichever is longer) prior to the first dose of study treatment; or use of moderate or strong CYP3A4 and/or CYP2C8 inducers within less than 5 elimination half-lives or 2 weeks (whichever is longer) prior to the first dose of study treatment; or anticipated need for continuous use of these medications during the study period (see Appendix 1 for examples of known strong or moderate CYP3A4 and CYP2C8 inhibitors/inducers and/or P-gp inhibitors).
- Cohorts B/C only: Disease progression within 3 months of the most recent endocrine therapy in the advanced/metastatic setting.
- History of or active inflammatory bowel disease requiring treatment, including ulcerative colitis, Crohn's disease, etc.
- Any other condition that, in the investigator's opinion, renders the participant unsuitable for participation in this trial.
Trial locations and contacts
6 sites in 1 country. Contact the study team or a site near you to ask about taking part.
6 sites in 1 country
China6 sites
Cancer Hospital, Chinese Academy of Medical Sciences
Beijing, Beijing Municipality, 100021
Binghe Xu, 010-87788787, cancergcp@163.com
The First Hospital of Jilin University
Changchun, Jilin, 130021
Nanya Wang, 0431-88783330, wangfei5780@126.com
Zhejiang Cancer Hospital
Hangzhou, Zhejiang, 310022
Hai Hu, 0571-88122482, lify1697@zjcc.org.cn
Anhui Provincial Cancer Hospital
Hefei, Anhui, 233004
Yueyin Pan, 0551-65320585, ahszlyygcp@163.com
Zhongshan Hospital Affiliated to Fudan University
Shanghai, Shanghai Municipality, 200032
Tianshu Liu, 021-31587858, gao.yiju@zs-hospital.sh.cn
Shanghai East Hospital
Shanghai, Shanghai Municipality, 200123
Ye Guo, 021-38804518-28329, shdfgcp@163.com
About this study
Official 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 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
- Being tested
- LAE118, Fulvestrant, Palbociclib
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LAE118Drug
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.
FulvestrantDrug
Fulvestrant is approved for the treatment of post-menopausal metastatic breast cancer following disease progression on therapy with an anti-estrogen therapy.
PalbociclibDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Cohort A (LAE118 monotherapy) | Experimental | Not described Receives: Drug: LAE118 |
| Cohort B (LAE118 plus fulvestrant) | Experimental | Not described Receives: Drug: LAE118; Drug: Fulvestrant |
| Cohort C (LAE118 plus fulvestrant and palbociclib) | Experimental | Not described Receives: Drug: LAE118; Drug: Fulvestrant; Drug: Palbociclib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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
Measured: Baseline to EOT, up to ~24 months
Change from baseline in PR interval as assessed by 12-lead ECG
Unit: bpm
Measured: Baseline to EOT, up to ~24 months
Change from baseline in QRS duration as assessed by 12-lead ECG
Unit: msec
Measured: Baseline to EOT, up to ~24 months
Change from baseline in heart rate as assessed by 12-lead ECG
Unit: bpm
Measured: Baseline to EOT, up to ~24 months
Change from baseline in systolic and diastolic blood pressure
Unit: mmHg
Measured: Baseline to EOT, up to ~24 months
Change from baseline in pulse rate
Unit: bpm
Measured: Baseline to EOT, up to ~24 months
Change from baseline in respiratory rate
Unit: breaths/min
Measured: Baseline to EOT, up to ~24 months
Change from baseline in body temperature
Unit: °C
Measured: 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.
Measured: 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).
Measured: 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
Measured: 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
Measured: 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
Measured: Baseline to EOT, up to ~24 months
Change from baseline in serum albumin and total protein
Unit: g/L
Measured: Baseline to EOT, up to ~24 months
Change from baseline in prothrombin time (PT) and activated partial thromboplastin time (aPTT)
Unit: seconds
Measured: Baseline to EOT, up to ~24 months
Change from baseline in international normalized ratio (INR)
Measured: Baseline to EOT, up to ~24 months
Change from baseline in fibrinogen
Unit: g/L
Measured: Baseline to EOT, up to ~24 months
Change from baseline in thyroid-stimulating hormone (TSH)
mIU/L
Measured: Baseline to EOT, up to ~24 months
Change from baseline in free triiodothyronine (FT3) and free thyroxine (FT4)
Unit: pmol/L
Measured: Baseline to EOT, up to ~24 months
Change from baseline in adrenal function parameters
Cortisol, ACTH, aldosterone, renin, and aldosterone/renin ratio.
Measured: Baseline to EOT, up to ~24 months
Change from baseline in troponin I/T
Unit: ng/mL
Measured: Baseline to EOT, up to ~24 months
Change from baseline in brain natriuretic peptide (BNP)
Unit: pg/mL
Measured: Baseline to EOT, up to ~24 months
Change from baseline in urinalysis parameters
Urine protein, glucose, ketones, occult blood, and specific gravity.
Measured: Baseline to EOT, up to ~24 months
Secondary outcomes (20)
Objective response rate (ORR)
Proportion of participants with CR or PR per RECIST v1.1 by investigator assessment.
Measured: Every 8 weeks from C1D1 to progression/EOT, up to ~24 months
Clinical benefit rate (CBR)
Proportion of participants with CR, PR, or SD ≥24 weeks per RECIST v1.1.
Measured: Every 8 weeks from C1D1, up to ~24 months
Duration of response (DOR)
Time from first CR/PR to disease progression or death per RECIST v1.1.
Measured: From first response to progression/death, up to ~24 months
Progression-free survival (PFS)
Time from first dose to disease progression per RECIST v1.1
Measured: C1D1 to progression/death, up to ~24 months
Peak plasma concentration (Cmax) of LAE118
Peak plasma concentration (Cmax) of LAE118 following single dose (Cycle 0 Day 1 for Cohort A; Cycle 1 Day 1 for Cohorts B and C) and multiple dose (Cycle 1 Day 15). Unit: ng/mL
Measured: Day 1 and Day 15: pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-dose.
Time to peak plasma concentration (Tmax) of LAE118
Time to peak plasma concentration (Tmax) of LAE118 following single dose on Day 1 and multiple doses on Day 15. Unit: hours
Measured: Day 1 and Day 15: pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-dose.
Area under the plasma concentration-time curve (AUC0-t, AUC0-∞, AUC0-24, AUCtau) of LAE118
Area under the plasma concentration-time curve (AUC0-t, AUC0-∞, AUC0-24, and AUCtau) of LAE118. AUC0-t and AUC0-∞ following both single and multiple doses; AUC0-24 following single dose only (Day 1); AUCtau following multiple doses only (Day 15). Unit: ng·h/mL
Measured: Day 1 (single-dose period) and Day 15 (multiple-dose period): pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-dose.
Terminal half-life (t1/2) of LAE118
Following single and multiple dose. Unit: hours
Measured: Day 1 (single-dose period) and Day 15 (multiple-dose period): pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-dose.
Apparent volume of distribution (Vz/F) of LAE118
Following single and multiple dose. Unit: L
Measured: Day 1 (single-dose period) and Day 15 (multiple-dose period): pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-dose.
Apparent clearance (CL/F) of LAE118
Following single and multiple dose. Unit: L/h
Measured: Day 1 (single-dose period) and Day 15 (multiple-dose period): pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-dose.
Trough plasma concentration (Ctrough) of LAE118
Trough plasma concentration (Ctrough) of LAE118 following multiple doses on Cycle 1 Day 15. Unit: ng/mL
Measured: Pre-dose on Day 15 of Cycle 1 (each cycle is 28 days).
Accumulation ratio (Racc) of LAE118
Accumulation ratio (Racc) of LAE118 following multiple doses (Cycle 1 Day 15 versus single-dose baseline). Unit: ratio
Measured: Single-dose baseline (Cycle 0 Day 1 for Cohort A; Cycle 1 Day 1 for Cohorts B and C) and multiple-dose steady-state (Cycle 1 Day 15 for all cohorts). Each cycle is 28 days.
Cmax of fulvestrant and palbociclib
Maximum plasma concentration (Cmax) of fulvestrant and palbociclib when co-administered with LAE118 on Cycle 1 Day 1 (single dose) and Cycle 1 Day 15 (multiple doses). Unit: ng/mL
Measured: Cycle 1 Day 1 and Cycle 1 Day 15: pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-dose. Each cycle is 28 days.
Tmax of fulvestrant and palbociclib
Time to maximum plasma concentration (Tmax) of fulvestrant and palbociclib when co-administered with LAE118 on Cycle 1 Day 1 (single dose) and Cycle 1 Day 15 (multiple doses). Unit: hours
Measured: Cycle 1 Day 1 and Cycle 1 Day 15: pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-dose. Each cycle is 28 days.
AUC0-t of fulvestrant and palbociclib
Area under the plasma concentration-time curve from time 0 to the last quantifiable time point (AUC0-t) of fulvestrant and palbociclib when co-administered with LAE118 on Cycle 1 Day 1 (single dose) and Cycle 1 Day 15 (multiple doses). Unit: ng·h/mL
Measured: Cycle 1 Day 1 and Cycle 1 Day 15: pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-dose. Each cycle is 28 days.
Change from baseline in fasting blood glucose
Unit: mmol/L
Measured: Baseline to EOT, up to ~24 months
Change from baseline in glycated hemoglobin (HbA1c) and glycated albumin
Unit: %
Measured: Baseline to EOT, up to ~24 months
Change from baseline in serum C-peptide
Unit: ng/mL
Measured: Baseline to EOT, up to ~24 months
Change from baseline in serum insulin
Unit: μIU/mL
Measured: Baseline to EOT, up to ~24 months
Change from baseline in QTcF interval and its relationship with plasma LAE118 concentration
Unit: msec
Measured: Baseline to EOT, up to ~24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Aug 2026
- Study startAug 2026 (estimated)
- Primary completionMar 2029 (estimated)
- Study completionDec 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Patients With Advanced Solid TumorsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 150 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Laekna Limited
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07787520
- Sponsor's protocol ID
- LAE118CN1002
- Status last verified
- Aug 2026
- First submitted
- 26 Jul 2026
- Last updated
- 26 Aug 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT07787520
- Acronym / sponsor ID
- LAE118CN1002
- Conditions
- Patients With Advanced Solid Tumors
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 150 participants (estimated)
- Lead sponsor
- Laekna LimitedIndustry (pharma, biotech, devices)
- Study start
- Aug 2026 (estimated)
- Primary completion
- Mar 2029 (estimated)
- Study completion
- Dec 2029 (estimated)
- First posted
- 26 Aug 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (45 listed)
- 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.
Key exclusion criteria (33 listed)
- 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:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LAE118LAЕ118 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. | Drug | Cohort A (LAE118 monotherapy), Cohort B (LAE118 plus fulvestrant), Cohort C (LAE118 plus fulvestrant and palbociclib) |
| FulvestrantFulvestrant is approved for the treatment of post-menopausal metastatic breast cancer following disease progression on therapy with an anti-estrogen therapy. | Drug | Cohort B (LAE118 plus fulvestrant), Cohort C (LAE118 plus fulvestrant and palbociclib) |
| PalbociclibPalbociclib 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. | Drug | Cohort C (LAE118 plus fulvestrant and palbociclib) |
Primary outcome
Number of participants with adverse events (AEs)
Time frame: From ICF signing to 30 days after last dose, up to ~24 months
Frequency and severity of AEs, including treatment-related AEs, serious AEs (SAEs), and AEs leading to treatment discontinuation, as assessed by CTCAE v5.0.
Number of participants with dose-limiting toxicities (DLTs)
Time frame: 35 days (Cohort A) / 28 days (Cohorts B and C)
Per protocol definition. DLT observation period: C0D1-C1D28 for Cohort A; C1D1-C1D28 for Cohorts B and C.
Change from baseline in QTcF interval as assessed by 12-lead ECG
Time frame: Baseline to EOT, up to ~24 months
Triplicate recordings within 10 min, ≥1 min apart. Fridericia's correction。 Unit: msec
Change from baseline in PR interval as assessed by 12-lead ECG
Time frame: Baseline to EOT, up to ~24 months
Unit: bpm
Change from baseline in QRS duration as assessed by 12-lead ECG
Time frame: Baseline to EOT, up to ~24 months
Unit: msec
Change from baseline in heart rate as assessed by 12-lead ECG
Time frame: Baseline to EOT, up to ~24 months
Unit: bpm
Change from baseline in systolic and diastolic blood pressure
Time frame: Baseline to EOT, up to ~24 months
Unit: mmHg
Change from baseline in pulse rate
Time frame: Baseline to EOT, up to ~24 months
Unit: bpm
Change from baseline in respiratory rate
Time frame: Baseline to EOT, up to ~24 months
Unit: breaths/min
Change from baseline in body temperature
Time frame: Baseline to EOT, up to ~24 months
Unit: °C
Change from baseline in physical examination findings
Time frame: Baseline to EOT, up to ~24 months
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.
Change from baseline in hematology parameters
Time frame: Baseline to EOT, up to ~24 months
WBC with differential (10⁹/L), RBC (10¹²/L), hemoglobin (g/L), hematocrit (%), platelet count (10⁹/L).
Change from baseline in serum chemistry - enzymes
Time frame: Baseline to EOT, up to ~24 months
ALT, AST, ALP, GGT, LDH, CK, CK-MB, amylase, lipase. Unit: U/L
Change from baseline in serum chemistry - bilirubin, creatinine, and bile acids
Time frame: Baseline to EOT, up to ~24 months
Total bilirubin, direct bilirubin, creatinine, bile acids. Unit: μmol/L
Change from baseline in serum chemistry - electrolytes and metabolites
Time frame: Baseline to EOT, up to ~24 months
Sodium, potassium, calcium, magnesium, phosphorus, BUN/urea, total cholesterol, HDL-C, LDL-C, triglycerides. Unit: mmol/L
Change from baseline in serum albumin and total protein
Time frame: Baseline to EOT, up to ~24 months
Unit: g/L
Change from baseline in prothrombin time (PT) and activated partial thromboplastin time (aPTT)
Time frame: Baseline to EOT, up to ~24 months
Unit: seconds
Change from baseline in international normalized ratio (INR)
Time frame: Baseline to EOT, up to ~24 months
Change from baseline in fibrinogen
Time frame: Baseline to EOT, up to ~24 months
Unit: g/L
Change from baseline in thyroid-stimulating hormone (TSH)
Time frame: Baseline to EOT, up to ~24 months
mIU/L
Change from baseline in free triiodothyronine (FT3) and free thyroxine (FT4)
Time frame: Baseline to EOT, up to ~24 months
Unit: pmol/L
Change from baseline in adrenal function parameters
Time frame: Baseline to EOT, up to ~24 months
Cortisol, ACTH, aldosterone, renin, and aldosterone/renin ratio.
Change from baseline in troponin I/T
Time frame: Baseline to EOT, up to ~24 months
Unit: ng/mL
Change from baseline in brain natriuretic peptide (BNP)
Time frame: Baseline to EOT, up to ~24 months
Unit: pg/mL
Change from baseline in urinalysis parameters
Time frame: Baseline to EOT, up to ~24 months
Urine protein, glucose, ketones, occult blood, and specific gravity.
20 secondary outcomes
Objective response rate (ORR)
Time frame: Every 8 weeks from C1D1 to progression/EOT, up to ~24 months
Clinical benefit rate (CBR)
Time frame: Every 8 weeks from C1D1, up to ~24 months
Duration of response (DOR)
Time frame: From first response to progression/death, up to ~24 months
Progression-free survival (PFS)
Time frame: C1D1 to progression/death, up to ~24 months
Peak plasma concentration (Cmax) of LAE118
Time frame: Day 1 and Day 15: pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-dose.
Time to peak plasma concentration (Tmax) of LAE118
Time frame: Day 1 and Day 15: pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-dose.
Area under the plasma concentration-time curve (AUC0-t, AUC0-∞, AUC0-24, AUCtau) of LAE118
Time frame: Day 1 (single-dose period) and Day 15 (multiple-dose period): pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-dose.
Terminal half-life (t1/2) of LAE118
Time frame: Day 1 (single-dose period) and Day 15 (multiple-dose period): pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-dose.
Apparent volume of distribution (Vz/F) of LAE118
Time frame: Day 1 (single-dose period) and Day 15 (multiple-dose period): pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-dose.
Apparent clearance (CL/F) of LAE118
Time frame: Day 1 (single-dose period) and Day 15 (multiple-dose period): pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-dose.
Trough plasma concentration (Ctrough) of LAE118
Time frame: Pre-dose on Day 15 of Cycle 1 (each cycle is 28 days).
Accumulation ratio (Racc) of LAE118
Time frame: Single-dose baseline (Cycle 0 Day 1 for Cohort A; Cycle 1 Day 1 for Cohorts B and C) and multiple-dose steady-state (Cycle 1 Day 15 for all cohorts). Each cycle is 28 days.
Cmax of fulvestrant and palbociclib
Time frame: Cycle 1 Day 1 and Cycle 1 Day 15: pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-dose. Each cycle is 28 days.
Tmax of fulvestrant and palbociclib
Time frame: Cycle 1 Day 1 and Cycle 1 Day 15: pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-dose. Each cycle is 28 days.
AUC0-t of fulvestrant and palbociclib
Time frame: Cycle 1 Day 1 and Cycle 1 Day 15: pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours post-dose. Each cycle is 28 days.
Change from baseline in fasting blood glucose
Time frame: Baseline to EOT, up to ~24 months
Change from baseline in glycated hemoglobin (HbA1c) and glycated albumin
Time frame: Baseline to EOT, up to ~24 months
Change from baseline in serum C-peptide
Time frame: Baseline to EOT, up to ~24 months
Change from baseline in serum insulin
Time frame: Baseline to EOT, up to ~24 months
Change from baseline in QTcF interval and its relationship with plasma LAE118 concentration
Time frame: Baseline to EOT, up to ~24 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Aug 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing LAE118, Fulvestrant and Palbociclib in people with Patients With Advanced Solid Tumors, run by Laekna Limited at 6 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 45 inclusion and 33 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 26 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Zheng Zhang (+8617602165910, zheng.zhang@laekna.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants with adverse events (AEs) (time frame: From ICF signing to 30 days after last dose, up to ~24 months). The study lists 25 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Aug 2026.