Health TrialsbyHealthPanel

A Study of APG-3288 in Relapsed/Refractory Blood Cancers

ConditionsRelapsed/Refractory Hematological MalignanciesRelapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Leukemia (CLL/SLLRelapsed/Refractory Diffuse Large B-cell Lymphoma (DLBCL; Including Richter Transformation)Relapsed/Refractory Mantle Cell Lymphoma (MCL)Relapsed/Refractory Waldenström Macroglobulinemia (WM)Relapsed/Refractory Marginal Zone Lymphoma (MZL)Relapsed/Refractory Follicular Lymphoma (FL)
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorAscentage Pharma Group Inc.

About this trial

This is a Phase I, multicenter, open-label, two-stage study of APG-3288 monotherapy, aiming to determine the Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of APG-3288 administered orally once daily in patients with relapsed/refractory (R/R) hematologic malignancies.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Eastern Cooperative Oncology Group (ECOG) status ≤ 1 in Part 1 (dose escalation), and ≤ 2 in Part 2 (dose expansion).

Part 1 (Dose Escalation): histologically or cytologically confirmed diagnosis of R/R CLL/SLL, DLBCL (including Richter Transformation), MCL, WM, MZL, or FL.

Prior systemic therapy: at least 2 prior lines of systemic therapy (including BTK inhibitor for approved indications) and who have failed or are not eligible for available therapies with established clinical benefit.

Measurable disease per response criteria specific to the malignant condition.

Disqualifiers

Concurrent anti-cancer therapy (chemotherapy, radiation therapy, surgery, immunotherapy, hormonal therapy, targeted therapy, biologic therapy, with the exception of hormones for hypothyroidism or estrogen replacement therapy, anti-estrogen analogs, agonists required to suppress serum testosterone levels).

Any investigational therapy within 14 days prior to the first dose of study drug or within 5 half-lives of the respective investigational drug (whichever is shorter).

Persistent toxicities from prior radiotherapy, targeted therapy, immunotherapy, or chemotherapy agents that have not recovered to Grade <2 (except for alopecia or vitiligo).

Symptomatic brain metastases due to tumor involvement of the central nervous system (CNS). Patients with CNS tumors who have been treated, are asymptomatic, and who have discontinued steroids (for the treatment of CNS tumors) for > 28 days may be enrolled.

Trial design

Design model

Sequential

Treatments tested in this trial

  • APG-3288

    Drug

    Orally administered daily; 28 days per cycle.

Treatment groups

180 Participants
are divided into 2 treatment groups
Group A: Part 1 (Dose Escalation Phase)Experimental treatment 1 intervention
Group B: Part 2 (Dose Expansion Phase)Experimental treatment 1 intervention

Trial outcomes

Primary outcomes

1

Incidence of dose-limiting toxicities (DLTs) at each dose level

A DLT is defined as any treatment-related adverse event (TRAE) meeting protocol-specified toxicity criteria occurring during the DLT evaluation period (Cycle 1). DLTs will be assessed in participants receiving escalating dose levels of APG-3288 to evaluate its safety and tolerability.

Time frame
From first dose through the end of Cycle 1 (e.g., Day 1 to Day 28)
2

Incidence of treatment emergent adverse events (TEAEs)

The incidence of treatment emergent adverse events (TEAEs), including Grade 3-5 TEAEs, serious adverse events (SAEs), TEAEs leading to dose interruption, dose reduction, or treatment discontinuation, and deaths, will be assessed in participants receiving APG-3288 in Part 1 (dose escalation) and Part 2 (dose expansion) of the study.

Time frame
From first dose of study treatment through 30 days after the last dose
3

Maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of APG 3288

The MTD and/or RP2D of APG-3288 will be determined during the dose escalation phase based on the incidence of DLTs, overall safety, tolerability, and available pharmacokinetic and pharmacodynamic data.

Time frame
During the dose escalation phase (Part 1)

Secondary outcomes

1

Peak plasma concentration (Cmax) of APG-3288

The assessment of maximum observed plasma concentration (Cmax) following administration of APG-3288.

Time frame
From first dose through 24 hours post-dose
2

Area Under the Plasma Concentration-Time Curve (AUC) of APG-3288

Area under the plasma concentration vs time curve (AUC0-t and AUC0-inf) of APG-3288 following administration APG-3288 at escalating dose levels.

Time frame
From first dose through last measurable concentration, assessed up to 24 hours post-dose
3

Pharmacodynamic (PD) profile of APG 3288

The pharmacodynamic effects of APG 3288 will be evaluated by changes in Bruton's tyrosine kinase (BTK) levels from baseline over time during treatment.

Time frame
From baseline of study treatment through 30 days after the last dose
4

Objective response rate (ORR)

ORR is defined as the proportion of patients who achieve partial response (PR) or better as assessed by the investigator at each efficacy assessment and upon disease progression or at end-of-treatment

Time frame
From first dose until the first documented disease progression or end of treatment, assessed up to 24 months

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Ascentage Pharma Group Inc.

Lead sponsor

Source ClinicalTrials.gov
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