What side effects are associated with this type of intervention?

Common treatments for lymphoma, including chemotherapy, immunotherapy, and targeted therapy, often result in side effects such as hematologic toxicities (neutropenia, anemia, thrombocytopenia), gastrointestinal issues (nausea, vomiting, diarrhea), fatigue, and increased risk of infections. Specific regimens like rituximab combined with chemotherapy can cause infusion reactions, cardiovascular issues (hypertension, atrial fibrillation), and non-hematologic toxicities (rash, fever).

What prior FDA approvals exist?

FDA-approved treatments for lymphoma that promote apoptosis in cancer cells include bortezomib and venetoclax. Bortezomib is a proteasome inhibitor that induces apoptosis by disrupting the proteasome pathway, leading to the accumulation of pro-apoptotic factors. Venetoclax is a BCL-2 inhibitor that promotes apoptosis by inhibiting the BCL-2 protein, which is often overexpressed in cancer cells to prevent cell death. These treatments, like ASTX660, aim to induce apoptosis in cancer cells, albeit through different mechanisms.

What other types of research exist?

Promising alternatives to ASTX660 for lymphoma patients include BTK inhibitors like ibrutinib, acalabrutinib, and zanubrutinib, which are effective in various types of lymphoma. Venetoclax, a BCL-2 inhibitor, is another option that promotes apoptosis in cancer cells. Additionally, CAR T-cell therapies targeting specific antigens on lymphoma cells are showing significant promise in clinical trials.

← Back to Search

Inhibitor

ASTX660 for Cancer

Phase 1 & 2

Waitlist Available

Research Sponsored by Taiho Oncology, Inc.

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Subjects with histologically or cytologically confirmed advanced solid tumors or lymphoma that is metastatic or unresectable, and for whom standard life-prolonging measures are not available. Specific tumor types that will be selected for study in Phase 2 are detailed in the protocol

Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2

Must not have

Known brain metastases, unless stable or previously treated

Known history of human immunodeficiency virus (HIV) infection, or seropositive results consistent with active hepatitis B virus (HBV) or active hepatitis C virus (HCV) infection

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 84 months

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing ASTX660, a new drug for patients with advanced cancers who have no other treatment options. It works by blocking proteins that help cancer cells survive, making it easier to kill them.

Who is the study for?

Adults with advanced solid tumors or lymphoma that can't be removed by surgery and have no standard life-prolonging treatments available. They must have acceptable organ function, not be pregnant or breastfeeding, agree to use effective contraception, and not have other serious health issues that could affect their safety or the study results.

What is being tested?

ASTX660 is being tested in this Phase 1/2 trial to find the safest dose, see how well it works against certain cancers, and understand its effects on the body. Participants will receive ASTX660 directly without comparison to another drug.

What are the potential side effects?

Specific side effects of ASTX660 are not listed but may include typical reactions seen with cancer drugs such as fatigue, nausea, risk of infection due to low blood counts, potential liver or kidney issues reflected by lab tests requirements.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

Select...

My cancer is advanced, cannot be surgically removed, and has no standard treatment options.

Select...

I can take care of myself and am up and about more than half of my waking hours.

Select...

My organ functions are within normal ranges according to recent tests.

Select...

My cancer is a specific type of lymphoma recognized by the WHO.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

My brain metastases are stable or have been treated.

Select...

I have HIV or active hepatitis B or C.

Select...

I do not have any severe illnesses or conditions that could risk my safety or affect the study results.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 84 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 84 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 84 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Efficacy (Phase 2) - antitumor activity assessed by disease control rate (DCR)

Efficacy (Phase 2) - antitumor activity assessed by objective response rate (ORR)

Safety (Phase 1) - number of subjects with AEs, DLTs, abnormal clinical laboratory values or physical exam results

Secondary study objectives

Assessment of target (cIAP1) engagement

Duration of antitumor response

Overall survival

+7 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

9Treatment groups

Experimental Treatment

Group I: Phase 2 - Cohort 6Experimental Treatment1 Intervention

Treatment with ASTX660 for cervical carcinoma not responsive or relapsed after standard therapy.

Group II: Phase 2 - Cohort 5Experimental Treatment1 Intervention

Treatment with ASTX660 for other tumor types that are characterized by a molecular feature that may confer sensitivity to ASTX660 (eg, oncogenic activation of the NF-κB pathway or documented amplification of the gene loci encoding c-IAP1 or c-IAP2), pending confirmation in writing by the Astex medical monitor.

Group III: Phase 2 - Cohort 4Experimental Treatment1 Intervention

Treatment with ASTX660 for relapsed or refractory cutaneous T-cell lymphoma (CTCL).

Group IV: Phase 2 - Cohort 3Experimental Treatment1 Intervention

Treatment with ASTX660 for progressive or relapsed peripheral T-cell lymphoma (PTCL).

Group V: Phase 2 - Cohort 2Experimental Treatment1 Intervention

Treatment with ASTX660 for relapsed or refractory diffuse large B-cell lymphoma (DLBCL).

Group VI: Phase 2 - Cohort 1Experimental Treatment1 Intervention

Treatment with ASTX660 for recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) not responsive or relapsed after standard therapy.

Group VII: Phase 1 - Part 3 (optional)Experimental Treatment1 Intervention

The purpose of the optional Part 3 is to allow for exploration of an alternative dosing regimen of ASTX660 based on emerging safety, PK, and pharmacodynamic (PD) data from Parts 1 and 2 (using the original every-other-week dosing regimen), with agreement of the DSRC. If Part 3 is conducted, the plan is to enroll up to 18 evaluable subjects in 1 or more cohorts using a standard 3+3 study design.

Group VIII: Phase 1 - Part 2 (completed)Experimental Treatment1 Intervention

Dose-expansion stage to confirm tolerability of ASTX660 at the RP2D using the every-other-week daily dosing regimen. Up to a total of 12 subjects (including the 3 or 6 subjects treated at the RP2D in Part 1) will be treated at the RP2D.

Group IX: Phase 1 - Part 1 (completed)Experimental Treatment1 Intervention

Dose-escalation stage to identify the MTD and the RP2D, defined as either the MTD or a dose below the MTD that the Data and Safety Review Committee (DSRC) agree shows adequate pharmacological evidence of target engagement and/or clinical activity. Subjects will receive ASTX660 once a day for 7 consecutive days every other week of each 28-day cycle (ie, \[7 days on/ 7 days off\] ×2; daily dosing on Days 1-7 and 15-21). The starting dose will be escalated stepwise in successive cohorts of 3 to 6 evaluable subjects each (standard 3+3 study design), until the RP2D is determined.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

ASTX660

2020

Completed Phase 1

~60

0 / 7Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Lymphoma treatments often target specific pathways to induce cancer cell death or inhibit their growth. Traditional chemotherapy, such as the DHAP regimen (dexamethasone, high-dose cytarabine, cisplatin), works by damaging the DNA of rapidly dividing cells, leading to cell death. Targeted therapies, like BTK inhibitors (e.g., ibrutinib), block specific proteins essential for cancer cell survival and proliferation. Immunotherapies, including anti-CD20 monoclonal antibodies (e.g., rituximab), enhance the immune system's ability to recognize and destroy cancer cells. ASTX660, a dual antagonist of cIAPs and XIAP, promotes apoptosis by inhibiting proteins that prevent cell death, making it a promising option for inducing cancer cell death in resistant lymphoma cases. These mechanisms are crucial for lymphoma patients as they offer multiple strategies to combat the disease, potentially improving outcomes and reducing resistance to treatment.

Signal Pathways and Therapeutic Prospects of Diffuse Large B Cell Lymphoma.Double hit diffuse large B-cell lymphomas: diagnostic and therapeutic challenges.Dexamethasone, high-dose cytarabine, and cisplatin in combination with rituximab as salvage treatment for patients with relapsed or refractory aggressive non-Hodgkin's lymphoma.