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

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.

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.

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.

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.

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.

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.

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.