A Study of AL58805 in Advanced, Metastatic GYN, STS or Breast Cancers

Phase 1b/2a Clinical Study of AL58805 Combining With Other Anti-tumor Agents in Advanced, Metastatic GYN, STS or Breast Cancers

This phase 1b/2a study evaluates AL58805, an oral investigational drug that blocks PI3K and mTOR signaling, in combination with one of three anticancer treatments: AL8326 (veonetinib), eribulin, or fulvestrant. Adults with recurrent, advanced, or metastatic endometrial cancer, cervical cancer, soft tissue sarcoma, or breast cancer may be eligible after at least one prior standard treatment has failed or could not be tolerated and no effective standard treatment option remains.

In phase 1b, small groups of participants will receive different doses of AL58805 with a fixed dose of the partner treatment to identify a recommended combination dose based on dose-limiting side effects. In phase 2a, disease-specific groups will receive the selected combination dose to estimate the objective response rate and further evaluate duration of response, progression-free survival, overall survival, safety, pharmacokinetics, and exploratory tumor biomarkers. Protocol treatment may continue for up to 12 months, with continued treatment beyond 12 months possible for participants who remain clinically benefiting and receive investigator and sponsor approval.

Study Overview

• Status: Not yet recruiting
• Conditions: Breast Neoplasms; Endometrial Neoplasms; Soft Tissue Sarcoma (STS)
• Intervention / Treatment: Drug: AL58805; Drug: AL8326; Drug: Eribulin; Drug: Fulvestrant

Detailed Description

AL-GB-805 is a global, multicenter, open-label, nonrandomized phase 1b/2a study of oral AL58805, a dual PI3K/mTOR inhibitor, combined with AL8326 (veonetinib), eribulin, or fulvestrant in adults with recurrent, advanced, or metastatic endometrial cancer, cervical cancer, soft tissue sarcoma (STS), or breast cancer for whom at least one prior standard treatment has failed or was not tolerated and no standard effective option remains.

Phase 1b uses a standard 3+3 dose-escalation/de-escalation design to select a regimen-specific recommended combination dose (RCD). AL58805 begins at 10 mg and may be increased to 20 mg or reduced to 5 mg based on dose-limiting toxicities (DLTs). Cohort A combines AL58805 with AL8326 40 mg in 28-day cycles; Cohort B combines AL58805 with eribulin 1.4 mg/m² intravenously on Days 1 and 8 of each 21-day cycle; and Cohort C combines AL58805 with fulvestrant 500 mg intramuscularly on Days 1, 15, and 29 and monthly thereafter in 28-day cycles. The RCD is the highest evaluated AL58805 dose at which fewer than 33% of evaluable participants experience a DLT during the first treatment cycle.

Phase 2a evaluates each regimen at its RCD. Cohort D includes separate endometrial cancer, cervical cancer, and STS groups receiving AL58805 plus AL8326. Cohort E includes separate STS and breast cancer groups receiving AL58805 plus eribulin. Cohort F includes an HR-positive or other eligible breast cancer group receiving AL58805 plus fulvestrant. Each disease-specific group initially enrolls 17 participants. Under the protocol-specified Simon two-stage design, a group with no objective responses stops for futility; a group with one or more objective responses may enroll 18 additional participants for a total of 35.

Tumor response is assessed by the investigator or local radiologist according to RECIST 1.1 at baseline and approximately every 8 weeks beginning on Cycle 3 Day 1. A complete response or partial response is confirmed by repeat imaging 4 to 6 weeks later. Treatment continues until disease progression, unacceptable toxicity, intercurrent illness that prevents safe treatment, withdrawal, sponsor discontinuation, or completion of 12 months of protocol treatment, whichever occurs first. Treatment beyond progression may be allowed when the investigator and sponsor determine that clinical benefit continues and urgent alternative intervention is not being delayed.

Participants who remain without progression and continue to benefit may receive study treatment beyond 12 months with investigator and sponsor approval under the protocol continued-access provisions or may later transition to a separate post-trial access protocol. Safety is monitored through the final study visit 4 to 5 weeks after the last study dose, and unresolved related adverse events and serious adverse events are followed until resolution or stabilization. Long-term follow-up includes vital status and subsequent anticancer therapy every 3 to 6 months.

• Study Type: Interventional
• Enrollment (Estimated): 138
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Queenie Yang, PhD; Phone Number: 8055301550; Email: queeniey@advenchen.com
• Study Contact Backup: Name: Judy Chen; Email: judc@advenchen.com

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas MD Anderson Cancer Center
      • Contact: Marium Kaukab, MBBS, CCRP; Phone Number: 713-792-9868; Email: surgery_regstartup@mdanderson.org
      • Principal Investigator: Jeffrey Andrew How, MD, MPH, MS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

- Subjects must meet all of the following inclusion criteria to be eligible for this study:

1. Age ≥ 18 years.

2. Histologically proven diagnosis of:

   1. Pathologically confirmed recurrent or metastatic solid tumors such as Endometrial cancer, Cervical cancer, STS and Breast cancer;

   2. Failure of at least 1 prior line of standard therapy (disease progression after treatment or intolerable treatment toxicities);

      - Patients with mismatch repair deficient/microsatellite-instability high tumors must have received a prior anti-PD-1/PD-L1 therapeutic agent.

   3. No standard and effective treatment available.
3. Have measurable disease defined by RECIST 1.1 confirmed by CT or MRI scan within 28 days of enrollment.
4. Life expectancy of ≥ 3 months at the time of enrollment.
5. Able to take orally administered study medication.

6. Have adequate baseline function and performance status within 28 days of enrollment:

   1. Bone marrow function: absolute neutrophil count (ANC) ≥ 1,500/mm3, platelets ≥75,000/mm3 and Hemoglobin ≥ 9g/dl.
   2. Renal function: creatinine ≤ 1.5 x institutional upper limit normal (ULN) or if creatinine is > 1.5 x ULN, creatinine clearance must be > 50 mL/min.
   3. Hepatic function: bilirubin ≤ 1.5 x ULN or ≤ 3.0 x ULN for subjects with Gilbert Syndrome; No liver metastasis, AST and ALT ≤ 2.5 × ULN; When liver metastasis occurs, AST and ALT ≤ 5.0 × ULN.
   4. Coagulation profile: international normalized ratio (INR) is ≤ 1.5 and an aPTT or PTT < 1.2 x ULN.
   5. ECOG performance ≤ 2
   6. Left ventricular ejection fraction (LVEF) ≥ 50%
7. No gastrointestinal diseases that affect drug absorption, such as malabsorption.
8. Women of child-bearing potential must agree to use contraceptive measures starting 1 week before C1D1 until 4 weeks after the last dose of study treatment and have a negative serum pregnancy test within 28 days of enrollment. The patient must be non-lactating; if a female patient has not yet reached menopause (menopause is defined as the cessation of menstruation for at least 12 consecutive months, with no other causes), and has not undergone sterilization (removal of the ovaries and/or uterus), she is considered to be fertile. Her sexual partner should use medically approved contraception during the treatment period and for 4 weeks after the treatment ends;
9. Provide written informed consent and authorization permitting release of Protected Health Information.
10. Ability and willingness to comply with the study protocol for the duration of the study and with follow-up procedures.

Exclusion Criteria:

• Subjects presenting with any of the following will not be included in the study:

  1. Treatment with an investigational agent within 28 days of enrollment.
  2. Cytotoxic chemotherapy, immunotherapy, or radiotherapy within 28 days (42 days in cases of mitomycin C, nitrosourea, lomustine) prior to enrollment.
  3. Concomitant treatment with strong inhibitors or inducers of CYP3A4, CYP2C9 and CYP2C19 within 14 days prior to enrollment and during the study unless there is an emergent or life- threatening medical condition that required it.
  4. Known allergy or intolerance to investigational drugs (e.g.AL58805, AL8326, eriblin, fulvestrant, etc.) and excipients. (For example, who have had intolerable adverse reactions such as local injection site pain or systemic discomfort after application of fulvestrant should be excluded.)
  5. Other invasive malignancies, with the exception of non-melanoma skin cancer, who had (or have) any evidence of other cancer presents within the last 5 years prior to enrollment or whose previous cancer treatment contraindicates this protocol therapy.
  6. Myocardial infarction or unstable angina within 6 months prior to enrollment; New York Heart Association (NYHA) Grade II or greater congestive heart failure; serious cardiac arrhythmia requiring medication; and Grade II or greater peripheral vascular disease.
  7. Pre-existing uncontrolled hypertension as documented by two baseline blood pressure readings taken at least five minutes apart, defined as systolic BP >150 mm Hg or diastolic BP>90 mm Hg pressure.
  8. QTc≥ 480 msec on screening ECG per Fridericia's formula.
  9. History of or existing risk factors for Torsades de pointes (TdP) (e.g., heart failure, hypokalemia, family history of Long QT Syndrome).
  10. Concurrent use of concomitant medications that prolong the QT/QTc interval.
  11. History of significant vascular disease (e.g. aortic aneurysm, aortic dissection, peripheral vascular disease).
  12. Patients with severe chronic obstructive pulmonary disease (COPD) in acute exacerbation, severe pulmonary fibrosis (such as idiopathic pulmonary fibrosis with rapid disease progression), etc.

  13. History or evidence upon physical examination of central nervous system (CNS) disease including primary brain tumor; seizures not controlled with standard medical therapy; and history of cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA), or subarachnoid hemorrhage within 6 months of enrollment.

      a. Subjects with metastatic CNS tumors may participate in this study if the subject is > 28 days from therapy completion (including radiation and/or surgery), is clinically stable at the time of study enrollment, and is not receiving corticosteroid therapy.

  14. History of neurological or psychiatric disorder, such as dementia, which in the investigator's assessment may prevent protocol compliance.
  15. Serious, non-healing wound, ulcer or bone fracture.
  16. Major surgical procedure within 28 days or minor surgical procedure performed within 7 days prior to C1D1 (a major surgical procedure is defined as requiring general anesthesia).
  17. Diabetes with poor blood sugar control. (If a patient with diabetes requires long-term use of insulin or hypoglycemic drugs, with no history of hypoglycemic drug dose adjustment in the past 1 month, they may be considered for inclusion after investigator assessment, even if their HbA1c is between 7.5% and 8.0%.)
  18. History of pancreatitis; history of renal disease that includes histologically confirmed glomerulonephritis, biopsy proven tubulointerstitial nephritis, crystal nephropathy or other renal insufficiencies.
  19. Proteinuria on urinalysis within 28 days of enrollment. Subjects discovered to have a urine protein of 1+ on dipstick or ≥ 30 mg/dl at baseline should undergo a 24-hour urine collection and demonstrate < 1000 mg protein per 24 hours or spot urine protein (mg/dL) to creatinine (mg/dL) ratio must be <1.0 to allow participation in the study.
  20. Clinically significant, uncontrolled hypokalemia, hypomagnesaemia, and/or hypocalcaemia.
  21. Hemoptysis within 3 months prior to enrollment.
  22. Acute or chronic liver disease, active hepatitis A, B, or C with known cirrhosis or liver dysfunction.
  23. Active bacterial infections requiring IV antibiotics (excluding uncomplicated urinary tract infection).
  24. Active bleeding or pathologic conditions that carry high risk of bleeding, such as known bleeding disorder, coagulopathy, or tumor involving major vessels.
  25. History of non-malignant gastrointestinal bleeding, gastric stress ulcerations, or peptic ulcer disease within the past 3-months prior to enrollment that in the opinion of the investigator may place the subject at risk of side effects on an anti-angiogenesis product.
  26. Intra-abdominal abscess within the last 3 months of enrollment.
  27. Ascites or pleural effusion (CTCAE5.0 ≥2)
  28. History of difficulty swallowing, malabsorption, active partial or complete bowel obstruction, or other chronic gastrointestinal disease or condition that may hamper compliance and/or absorption.
  29. Anticoagulation therapy with warfarin. Subjects treated with heparin, low molecular weight heparin, or any other anticoagulant may be included provided the subject has been on a stable therapeutic dose of the anticoagulant for at least 14 days prior to enrollment.
  30. Known history of human immunodeficiency virus infection (HIV) with viral load is detectable.
  31. HBsAg-positive patients with HBV DNA ≥ 104 copies or ≥ 2000IU/mL, antiviral and liver protection treatment should be performed first, and they can be enrolled only when HBV-DNA ≤ 104 copies/mL (2000IU/mL), and continue to take antiviral drugs, monitor liver function and hepatitis B virus load; HCV antibody positive and HCV-RNA positive.
  32. The investigator deems that the subject is not suitable to participate in this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: P1b-Cohort A: (AL58805 + AL8326 Endometrial/Cervical/STS cancer, RCD-A); This cohort evaluates the safety and tolerability of AL8326 (40 mg) in combination with AL58805 (10 mg) in a 3+3 DLT evaluation design. If DLT occurs, AL58805 will be reduced to 5 mg; If no DLT occurs at 10 mg, it will be escalated to 20 mg.	Drug: AL58805; AL58805 is a novel chemical-structure antitumor drug with independent intellectual property rights. It functions as a novel dual-target PI3K/mTOR kinase inhibitor, exhibiting effects such as inhibiting tumor cell growth and proliferation, suppressing tumor nutrient metabolism, and exerting anti-angiogenic activity. By simultaneously inhibiting both PI3K and mTOR, it completely blocks the entire PI3K/AKT/mTOR signaling pathway at relatively low safe doses, thereby enhancing antitumor efficacy.; Drug: AL8326; AL8326 is a novel small molecule multi-receptor tyrosine kinase inhibitor, which shows highly selective inhibition of fibroblast growth factor receptor (FGFr1, FGFr2, FGFr3), vascular endothelial growth factor receptor (VEGFr1, VEGFr2, VEGFr3) and Aurora-B.
Experimental: P1b-Cohort B: (AL58805 + Eribulin, Soft Tissue Sarcoma/Breast Cancer, RCD-B); This cohort evaluates the safety and tolerability of Eribulin (1.4 mg/m²IV; 21 day-cycles of local standard) in combination with AL58805(10 mg). If DLT occurs, AL58805 will be reduced to 5 mg; If no DLT occurs at 10 mg bid, it will be escalated to 20 mg.	Drug: AL58805; AL58805 is a novel chemical-structure antitumor drug with independent intellectual property rights. It functions as a novel dual-target PI3K/mTOR kinase inhibitor, exhibiting effects such as inhibiting tumor cell growth and proliferation, suppressing tumor nutrient metabolism, and exerting anti-angiogenic activity. By simultaneously inhibiting both PI3K and mTOR, it completely blocks the entire PI3K/AKT/mTOR signaling pathway at relatively low safe doses, thereby enhancing antitumor efficacy.; Drug: Eribulin; Eribulin Mesylate is a microtubule dynamics inhibitor used in the treatment of certain advanced solid tumors. It works by binding to tubulin, inhibiting the dynamic assembly and disassembly of microtubules, blocking mitosis in cancer cells, and inducing apoptosis.
Experimental: P1b-Cohort C: (AL58805 + Fulvestrant, HR+/other Breast Cancer, RCD-C); This cohort evaluates the safety and tolerability of Fulvestrant (500 mg IM) in combination with AL58805 (10 mg). If DLT occurs, AL58805 will be reduced to 5 mg; If no DLT occurs at 10 mg, it will be escalated to 20 mg.	Drug: AL58805; AL58805 is a novel chemical-structure antitumor drug with independent intellectual property rights. It functions as a novel dual-target PI3K/mTOR kinase inhibitor, exhibiting effects such as inhibiting tumor cell growth and proliferation, suppressing tumor nutrient metabolism, and exerting anti-angiogenic activity. By simultaneously inhibiting both PI3K and mTOR, it completely blocks the entire PI3K/AKT/mTOR signaling pathway at relatively low safe doses, thereby enhancing antitumor efficacy.; Drug: Fulvestrant; Fulvestrant is a class of estrogen receptor antagonist, estrogen receptor downregulation agents for anti-breast cancer treatment.
Experimental: P2a-Cohort D: (AL58805 + AL8326, Endometrial/Cervical/STS cancer); This cohort evaluates the safety and efficacy of AL8326 + AL58805 at RCD-A (determined from Cohort A) in patients with advanced Endometrial (n=17), Cervical (n=17) and STS cancer (n=17) (≥2nd line, age ≥18). Treatment continues until PD or intolerability.	Drug: AL58805; AL58805 is a novel chemical-structure antitumor drug with independent intellectual property rights. It functions as a novel dual-target PI3K/mTOR kinase inhibitor, exhibiting effects such as inhibiting tumor cell growth and proliferation, suppressing tumor nutrient metabolism, and exerting anti-angiogenic activity. By simultaneously inhibiting both PI3K and mTOR, it completely blocks the entire PI3K/AKT/mTOR signaling pathway at relatively low safe doses, thereby enhancing antitumor efficacy.; Drug: AL8326; AL8326 is a novel small molecule multi-receptor tyrosine kinase inhibitor, which shows highly selective inhibition of fibroblast growth factor receptor (FGFr1, FGFr2, FGFr3), vascular endothelial growth factor receptor (VEGFr1, VEGFr2, VEGFr3) and Aurora-B.
Experimental: P2a-Cohort E: (AL58805 + Eribulin, Breast cancer/Soft Tissue Sarcoma); This cohort evaluates the safety and efficacy of Eribulin + AL58805 at RCD-B (determined from Cohort B) in patients with STS (n=17) and Breast cancer (n=17) (≥2nd-line, age ≥18). Treatment continues until PD or intolerability.	Drug: AL58805; AL58805 is a novel chemical-structure antitumor drug with independent intellectual property rights. It functions as a novel dual-target PI3K/mTOR kinase inhibitor, exhibiting effects such as inhibiting tumor cell growth and proliferation, suppressing tumor nutrient metabolism, and exerting anti-angiogenic activity. By simultaneously inhibiting both PI3K and mTOR, it completely blocks the entire PI3K/AKT/mTOR signaling pathway at relatively low safe doses, thereby enhancing antitumor efficacy.; Drug: Eribulin; Eribulin Mesylate is a microtubule dynamics inhibitor used in the treatment of certain advanced solid tumors. It works by binding to tubulin, inhibiting the dynamic assembly and disassembly of microtubules, blocking mitosis in cancer cells, and inducing apoptosis.
Experimental: P2a-Cohort F: (AL58805 + Fulvestrant, HR+/other Breast Cancer); This cohort evaluates the safety and efficacy of Fulvestrant + AL58805 at RCD-C(determined from Cohort C) in patients with HR+/other Breast cancer (≥2nd-line, age ≥18). Treatment continues until PD or intolerability (n=17). Other breast cancer in phase 1b/2a: HER2-, PIK3CA mutant and PIK3CA Wild-Type etc.	Drug: AL58805; AL58805 is a novel chemical-structure antitumor drug with independent intellectual property rights. It functions as a novel dual-target PI3K/mTOR kinase inhibitor, exhibiting effects such as inhibiting tumor cell growth and proliferation, suppressing tumor nutrient metabolism, and exerting anti-angiogenic activity. By simultaneously inhibiting both PI3K and mTOR, it completely blocks the entire PI3K/AKT/mTOR signaling pathway at relatively low safe doses, thereby enhancing antitumor efficacy.; Drug: Fulvestrant; Fulvestrant is a class of estrogen receptor antagonist, estrogen receptor downregulation agents for anti-breast cancer treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recommended Combination Dose (RCD)	Determine the recommended combination dose (RCD) of AL58805 in combination with AL8326, Eribulin, or Fulvestrant based on the incidence of dose-limiting toxicities (DLTs) during Phase 1b. The RCD is defined as the highest evaluated dose level at which fewer than 33% of participants experience a DLT.	36 months
Objective Tumor Response Rate (ORR)	Percentage of participants who achieve a Complete Response (CR) or Partial Response (PR) as the best overall tumor response according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.	36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic endpoint: Time to Maximum Plasma Concentration (Tmax)	Time from study drug administration to the observed maximum plasma concentration (Tmax) of AL58805, and of AL8326 where applicable, determined from protocol-specified pharmacokinetic sampling.	36 months
Pharmacokinetic endpoint: Maximum Observed Plasma Concentration (Cmax)	Maximum observed plasma concentration (Cmax) of AL58805, and of AL8326 where applicable, determined from plasma concentration-time data collected at protocol-specified pharmacokinetic sampling time points.	36 months
Pharmacokinetic endpoint: Area Under the Plasma Concentration-Time Curve (AUC)	Area under the plasma concentration-time curve (AUC) of AL58805, and of AL8326 where applicable, calculated from plasma concentration-time data collected at protocol-specified pharmacokinetic sampling time points.	36 months
Duration of Response (DOR)	Time from the date of the first documented objective response, defined as Complete Response (CR) or Partial Response (PR), to the date of documented disease progression or death from any cause, whichever occurs first, according to RECIST version 1.1.	36 months
Progression-Free Survival (PFS)	Time from Cycle 1 Day 1 (C1D1) to the first documented disease progression or death from any cause, whichever occurs first.	36 months
Overall Survival (OS)	Time from Cycle 1 Day 1 (C1D1) to death from any cause.	36 months

Collaborators and Investigators

• Sponsor: Advenchen Pharmaceuticals, LLC.
• Investigators: Study Director: Judy Chen, Advenchen Pharmaceuticals, LLC.; Principal Investigator: Jeffrey A How, MD, UT MD Anderson

Publications and helpful links

General Publications

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Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): September 1, 2030
• Study Completion (Estimated): September 1, 2031

Study Registration Dates

• First Submitted: August 12, 2026
• First Submitted That Met QC Criteria: September 3, 2026
• First Posted (Actual): September 10, 2026

Study Record Updates

• Last Update Posted (Actual): September 10, 2026
• Last Update Submitted That Met QC Criteria: September 3, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Neoplasms by Histologic Type; Uterine Diseases; Genital Diseases, Female; Genital Neoplasms, Female; Skin Diseases; Breast Diseases; Uterine Neoplasms; Neoplasms, Connective and Soft Tissue; Skin and Connective Tissue Diseases; Breast Neoplasms; Sarcoma; Endometrial Neoplasms; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Polycyclic Compounds; Steroids; Fused-Ring Compounds; Estradiol; Estrenes; Estranes; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Fulvestrant; eribulin
• Other Study ID Numbers: AL-GB-805

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No