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

Conditions

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

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

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.
• 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.
• 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.
• 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.

Study Details

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.

Key Dates

First listed

Sep 10, 2026

Start date

Sep 1, 2026

Status verified

Aug 2026

Primary completion

Sep 1, 2030

Completion

Sep 1, 2031

Study Design

Enrollment

138 participants (estimated)

Allocation

NON_RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

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

Primary Outcome Measure

Recommended combination dose (RCD) [ Time Frame: 36 months ]

Central Contacts

• Queenie Yang, PhD
  8055301550
  [email protected]
• Judy Chen
  [email protected]

Locations (1)

Find similar trials in Houston, TX

Related Studies

• INdividualized Screening Trial of Innovative Glioblastoma Therapy (INSIGhT)
  PHASE2 · Recruiting · David Reardon, MD · Boston, Massachusetts
• SYNERGY-AI: Artificial Intelligence Based Precision Oncology Clinical Trial Matching and Registry
  Recruiting · Massive Bio, Inc. · Birmingham, Alabama
• HSV-tk and XRT and Chemotherapy for Newly Diagnosed GBM
  PHASE1/PHASE2 · Recruiting · The Methodist Hospital Research Institute · Houston, Texas
• A Trial to Evaluate Multiple Regimens in Newly Diagnosed and Recurrent Glioblastoma
  PHASE2/PHASE3 · Recruiting · Global Coalition for Adaptive Research · Birmingham, Alabama