A Study of Catequentinib Hydrochloride (AL3818) in Endometrial, LGSOC, STS or GBM Cancers

NCT07811297 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: AL-GB-900
• Study Type: interventional
• Target: 138
• Locations: 1 country
• Sites: 1

Brief Summary

This phase 1b/2a study evaluates the investigational oral drug catequentinib hydrochloride (AL3818), given alone or with AL58805, temozolomide, or lomustine (CCNU), in adults with advanced or metastatic solid tumors. The phase 1b part will identify doses that can be given safely based on side effects during the first treatment cycle. The phase 2a part will estimate whether the treatments shrink non-brain tumors or keep glioblastoma from worsening for at least 6 months. The study is open label, which means participants and study investigators will know which treatment is given. Tumor response will be assessed with RECIST version 1.1. The study will also evaluate how the investigational drugs move through the body, the duration of tumor response, progression-free survival, overall survival, and treatment safety.

Conditions

Endometrial Neoplasms; Ovarian Neoplasms; Soft Tissue Sarcoma (STS); Glioblastoma

Outcome Measures

Primary Outcomes (2)

• Recommended combination dose (RCD)

  Determine the recommended combination dose (RCD) of AL3818 in combination with other anti-tumor agents based on evaluation of dose-limiting toxicity (DLT) events during Phase 1b.

  36 months

• Objective Tumor Response Rate (ORR)

  Evaluate the proportion of participants who achieve Complete Response (CR) or Partial Response (PR) as the best overall tumor response according to RECIST version 1.1; tumor response in participants with GBM is assessed according to RANO 2.0.

  36 months

Secondary Outcomes (6)

• Pharmacokinetic endpoint: Time to Maximum Plasma Concentration (Tmax)

  36 months

• Pharmacokinetic endpoint: Peak Plasma Concentration (Cmax)

  36 months

• Pharmacokinetic endpoint: Area Under the Curve (AUC)

  36 months

• Duration of Response (DOR)

  36 months

• Progression-Free Survival (PFS)

  36 months

Study Arms (7)

P1b.1-A1: Cohort A1 (Monotherapy RP2D determination, Solid Tumors)

EXPERIMENTAL

This cohort evaluates the safety and tolerability of oral AL3818 monotherapy (12 mg, 4 days on/3 days off) in a 28-day per cycle for patients with advanced solid tumors such as NSCLC, SCLC, STS, Thyroid, Endometrial, LGSOC, Breast cancer patients who require ≥2nd-line therapy or have no standard of care (SOC) treatment options (age ≥18). A 3+3 design is used to assess dose-limiting toxicities (DLTs), escalate to 14 mg if no DLT or de-escalate to 10 mg if DLT observed, to determine the recommended monotherapy Phase II dose (RP2D). LGSOC patient can use AL3818 for1st line treatment at PI's discretion.

Drug: AL3818

P1b.1-A2: Cohort A2 (Combination therapy RP2D determination, Endometrial, LGSOC or STS)

EXPERIMENTAL

This cohort evaluates the safety and tolerability of oral AL3818 (12mg or 10mg, 4 days on/3 days off, based on above RP2D-2mg) in combination with AL58805 (10 mg) in a 28-day per cycle for patients with STS or Endometrial patients. A 3+3 design is used to assess dose-limiting toxicities (DLTs), escalate AL58805 to 20mg if no DLT or deescalate AL3818 to 10 mg if DLT observed, to determine the recommended combination therapy Phase II dose (RP2D). LGSOC patient can use AL3818 for1st line treatment at PI's discretion.

Drug: AL58805; Drug: AL3818

P1b.2-B1: Cohort B1 (Monotherapy RP2D determination, Glioblastoma)

EXPERIMENTAL

This cohort evaluates the safety and tolerability of AL3818 monotherapy (12mg, 4 days on/3 days off) for glioblastoma (GBM) patients. A 3+3 design is used to assess dose-limiting toxicities (DLTs), de-escalate to 10 mg if DLT observed. If no DLT observed, Patients will go next cohort P1b.2-B2 for combination study.

Drug: AL3818

P1b.2-B2: Cohort B2 (Combination therapy RP2D-B determination, Glioblastoma)

EXPERIMENTAL

This cohort evaluates the safety and tolerability of AL3818 12mg (or 10 mg), 4 days on/3 days off (if passed DLT) in combination with Temozolomide (150 mg/m², 5 days on/23 days off) in a 28-day cycle for up to 6 cycles of Temozolomide, or CCNU (90 mg/m²) in a 8-week cycle for up to 6 cycles of CCNU for glioblastoma (GBM) patients. A 3+3 DLT assessment will determine the recommended combination dose (RCD) with RCD-B1 for Temozolomide or RCD-B2 for CCNU respectively. Temozolomide or CCNU is sequentially enrolled at PI's discretion based on patients meeting eligibility criteria. If DLT is observed in this combination therapy, the AL3818 dose will be further reduced to next -2 mg level. Patients from Cohort B1 without DLTs in the first cycle (28 days for Temozolomide or 56 days for CCNU) may transition to this Cohort B2. RCD-B1 and RCD-B2 will be used in phase 2a study.

Drug: AL3818; Drug: Temozolomide (TMZ); Drug: CCNU

P2a.3-C: Cohort C (AL3818 monotherapy, Endometrial, LGSOC cancer)

EXPERIMENTAL

This cohort evaluates the preliminary efficacy and safety of AL3818 monotherapy at the RP2D (determined from Cohort A, 4 days on/3 days off in 28-day cycles) in patients with advanced endometrial, LGSOC cancer (≥2nd-line, age ≥18) with TP53 mutated adenocarcinoma, TP53 carcinosarcoma and TP53 wild type. Treatment continues until disease progression (PD) or intolerability (n=17 for each TP53 and LGSOC group). LGSOC patient can use AL3818 for1st line treatment at PI's discretion.

Drug: AL3818

P2a.3-D: Cohort D (AL58805 + AL3818, Endometrial, LGSOC and STS)

EXPERIMENTAL

This cohort evaluates the safety and efficacy of AL3818 + AL58805 at RP2D (determined from Cohort A2) in patients with advanced endometrial, LGSOC or STS cancer (≥2nd-line, age ≥18). Enrollment n=17 each indication, Optional biomarker research may be included to identify mutations of PIK3CA, PTEN, ARID1A and homologous recombination deficiency. LGSOC patient can use AL3818 for1st line treatment at PI's discretion.

Drug: AL58805; Drug: AL3818

P2a.3-E: Cohort E (AL3818 + temozolomide or CCNU, Glioblastoma)

EXPERIMENTAL

This cohort evaluates the safety and efficacy of AL3818 (RCD-B1 and RCD-B2 from Cohort B1 and B2) qd/4 days on, 3 days off) in combination with Temozolomide (150 mg/m², 5 days on/23 days off) all for 28 days per cycle for up to 6 cycles of Temozolomide, or CCNU (90 mg/m²) in a 8-week cycle for up to 6 cycles of CCNU to PD or intolerability for ≥ 2nd line treatment (age: ≥ 18) GBM patients. Enrollment is at n=17 individually for Temozolomide or CCNU which is sequentially enrolled at PI's discretion.

Drug: AL3818; Drug: Temozolomide (TMZ); Drug: CCNU

Interventions

AL58805 DRUG

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.

P1b.1-A2: Cohort A2 (Combination therapy RP2D determination, Endometrial, LGSOC or STS); P2a.3-D: Cohort D (AL58805 + AL3818, Endometrial, LGSOC and STS)

AL3818 DRUG

AL3818 is a novel small molecule dual receptor tyrosine kinase inhibitor, which shows highly selective inhibition of fibroblast growth factor receptor (FGFr) and vascular endothelial growth factor receptor (VEGFR). Preclinical studies of this agent in mouse models, including various cancer xenografts, have demonstrated that treatment of tumor-bearing mice with AL3818 induces tumor reductions.

P1b.1-A1: Cohort A1 (Monotherapy RP2D determination, Solid Tumors); P1b.1-A2: Cohort A2 (Combination therapy RP2D determination, Endometrial, LGSOC or STS); P1b.2-B1: Cohort B1 (Monotherapy RP2D determination, Glioblastoma); P1b.2-B2: Cohort B2 (Combination therapy RP2D-B determination, Glioblastoma); P2a.3-C: Cohort C (AL3818 monotherapy, Endometrial, LGSOC cancer); P2a.3-D: Cohort D (AL58805 + AL3818, Endometrial, LGSOC and STS); P2a.3-E: Cohort E (AL3818 + temozolomide or CCNU, Glioblastoma)

Temozolomide (TMZ) DRUG

Temozolomide is an alkylating agent, which metabolizes to generate active substance methyl triazene imidazole formamide (MTIC), which interferes with the replication and repair of tumor cell DNA and induces apoptosis of cancer cells.

P1b.2-B2: Cohort B2 (Combination therapy RP2D-B determination, Glioblastoma); P2a.3-E: Cohort E (AL3818 + temozolomide or CCNU, Glioblastoma)

CCNU DRUG

CCNU is an alkylating agent that works by damaging cancer cell DNA, ultimately leading to cell death. It is lipid-soluble, allowing it to cross the blood-brain barrier, which is crucial for treating brain tumors.

P1b.2-B2: Cohort B2 (Combination therapy RP2D-B determination, Glioblastoma); P2a.3-E: Cohort E (AL3818 + temozolomide or CCNU, Glioblastoma)

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.
• Histologically proven diagnosis of:
• Pathologically confirmed recurrent or metastatic solid tumors such as NSCLC, SCLC, STS, Thyroid, Endometrial, LGSOC, GBM and breast cancer (Phase 2a: STS, Endometrial, LGSOC and GBM ); GBM can only have histological confirmation of diagnosis;
• Failure of at least 1 prior line of standard therapy (disease progression after treatment or intolerable treatment toxicities); concurrent chemoradiation therapy and adjuvant chemotherapy such as containing temozolomide will be considered as 1 line of prior therapy
• no standard or effective treatment available.
• Measurable disease is not required in phase 1b. Have measurable disease defined by RECIST 1.1 (or RANO 2.0 for GBM by MRI) confirmed by CT or MRI scan within 28 days of enrollment in phase 2a.
• Life expectancy of ≥ 3 months at the time of enrollment.
• Able to take orally administered study medication.
• Have adequate baseline function and performance status within 28 days of enrollment:
• Bone marrow function: absolute neutrophil count (ANC) ≥ 1,500/mm3, platelets ≥75,000/mm3 and Hemoglobin ≥ 9g/dl.
• 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.
• 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.
• Coagulation profile: international normalized ratio (INR) is ≤ 1.5 and an aPTT or PTT \< 1.2 x ULN.
• ECOG performance ≤ 2
• Left ventricular ejection fraction (LVEF) ≥ 50%

You may not qualify if:

• Subjects presenting with any of the following will not be included in the study:
• Treatment with an investigational agent within 28 days of enrollment.
• Cytotoxic chemotherapy, targeted therapies, immunotherapy, or radiotherapy within 28 days (42 days in cases of mitomycin C, nitrosourea, lomustine) prior to enrollment. Prior bevacizumab or other antiangiogenic therapies for phase 2 part of the GBM cohort (however, use of bevacizumab for radiation necrosis or toxicity is allowed unless it is within 28 days prior to enrollment).
• 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.
• Known allergy or intolerance to investigational drugs (e.g., AL3818, AL58805, temozolomide, CCNU, etc.) and excipients. (For example, patients who have had severe allergic reactions such as rash or anaphylactic shock after previous use of temozolomide.)
• 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.
• 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.
• 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.
• QTc ≥ 480 msec on screening ECG per Fridericia's formula.
• History of or existing risk factors for Torsades de pointes (TdP) (e.g., heart failure, hypokalemia, family history of Long QT Syndrome).
• Concurrent use of concomitant medications that prolong the QT/QTc interval.
• History of significant vascular disease (e.g. aortic aneurysm, aortic dissection, peripheral vascular disease).
• Patients with severe chronic obstructive pulmonary disease (COPD) in acute exacerbation, severe pulmonary fibrosis (such as idiopathic pulmonary fibrosis with rapid disease progression), etc.
• History or evidence upon physical examination of central nervous system (CNS) disease including primary brain tumor (not applicable for GBM cohorts); 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.

Sponsors & Collaborators

• Advenchen Pharmaceuticals, LLC.: lead

Study Sites (1)

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (3)

• Ellingson BM, Wen PY, Cloughesy TF. Modified Criteria for Radiographic Response Assessment in Glioblastoma Clinical Trials. Neurotherapeutics. 2017 Apr;14(2):307-320. doi: 10.1007/s13311-016-0507-6.

  PMID: 28108885 BACKGROUND

• Glaviano A, Foo ASC, Lam HY, Yap KCH, Jacot W, Jones RH, Eng H, Nair MG, Makvandi P, Geoerger B, Kulke MH, Baird RD, Prabhu JS, Carbone D, Pecoraro C, Teh DBL, Sethi G, Cavalieri V, Lin KH, Javidi-Sharifi NR, Toska E, Davids MS, Brown JR, Diana P, Stebbing J, Fruman DA, Kumar AP. PI3K/AKT/mTOR signaling transduction pathway and targeted therapies in cancer. Mol Cancer. 2023 Aug 18;22(1):138. doi: 10.1186/s12943-023-01827-6.

  PMID: 37596643 BACKGROUND

• Lai S, Li P, Liu X, Liu G, Xie T, Zhang X, Wang X, Huang J, Tang Y, Liu Z, Shen G, Li C, Lu F, Wang L, Jiang F, Sun C, Chen Y, Chen M. Efficacy and safety of anlotinib combined with the STUPP regimen in patients with newly diagnosed glioblastoma: a multicenter, single-arm, phase II trial. Cancer Biol Med. 2024 Mar 4;21(5):433-44. doi: 10.20892/j.issn.2095-3941.2023.0373.

  PMID: 38445445 BACKGROUND

MeSH Terms

Conditions

Endometrial Neoplasms; Ovarian Neoplasms; Sarcoma; Glioblastoma

Interventions

anlotinib; Temozolomide; Lomustine

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Endocrine System Diseases; Gonadal Disorders; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nitrosourea Compounds; Urea; Amides; Nitroso Compounds

Study Officials

• Judy Chen

  Advenchen Pharmaceuticals, LLC.

  STUDY DIRECTOR

• Carlos K Matsuoka, MD

  UT MD Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Queenie Yang, PhD

CONTACT

8055301550; queeniey@advenchen.com

Judy Chen

CONTACT

judc@advenchen.com

Study Design

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

Study Record Dates

• First Submitted: August 12, 2026
• First Posted: September 10, 2026
• Study Start: September 1, 2026
• Primary Completion (Estimated): September 1, 2030
• Study Completion (Estimated): September 1, 2031
• Last Updated: September 10, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)