A Study of AL58805 in Advanced, Metastatic GYN, STS or Breast Cancers
Trial statusNot yet recruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorAdvenchen Pharmaceuticals, LLC.
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Age ≥ 18 years.
Pathologically confirmed recurrent or metastatic solid tumors such as Endometrial cancer, Cervical cancer, STS and Breast cancer;
Failure of at least 1 prior line of standard therapy (disease progression after treatment or intolerable treatment toxicities);
No standard and effective treatment available.
Disqualifiers
Treatment with an investigational agent within 28 days of enrollment.
Cytotoxic chemotherapy, immunotherapy, or radiotherapy within 28 days (42 days in cases of mitomycin C, nitrosourea, lomustine) 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.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.)
Trial design
Design model
Parallel
Treatments tested in this trial
AL58805
DrugAL58805 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.
AL8326
DrugAL8326 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.
Eribulin
DrugEribulin 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.
Fulvestrant
DrugFulvestrant is a class of estrogen receptor antagonist, estrogen receptor downregulation agents for anti-breast cancer treatment.
Treatment groups
138 Participants
are divided into 6 treatment groups6
Treatment groupsSee each treatment group below.
Group A: P1b-Cohort A: (AL58805 + AL8326 Endometrial/Cervical/STS cancer, RCD-A)Experimental treatment 2 interventions
Group B: P1b-Cohort B: (AL58805 + Eribulin, Soft Tissue Sarcoma/Breast Cancer, RCD-B)Experimental treatment 2 interventions
Group C: P1b-Cohort C: (AL58805 + Fulvestrant, HR+/other Breast Cancer, RCD-C)Experimental treatment 2 interventions
Group D: P2a-Cohort D: (AL58805 + AL8326, Endometrial/Cervical/STS cancer)Experimental treatment 2 interventions
Group E: P2a-Cohort E: (AL58805 + Eribulin, Breast cancer/Soft Tissue Sarcoma)Experimental treatment 2 interventions
Group F: P2a-Cohort F: (AL58805 + Fulvestrant, HR+/other Breast Cancer)Experimental treatment 2 interventions
Trial outcomes
Primary outcomes
1
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.
Time frame
36 months2
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.
Time frame
36 monthsSecondary outcomes
1
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.
Time frame
36 months2
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.
Time frame
36 months3
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.
Time frame
36 months4
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.
Time frame
36 monthsSponsors and contacts
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Source ClinicalTrials.gov
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