ASTX660 for Cancer

Not currently recruiting at 72 trial locations

Overseen By Purvi Monani

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Taiho Oncology, Inc.

Must not be taking: QT prolonging drugs

Disqualifiers: Cardiac disease, HIV, Hepatitis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 7

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called ASTX660, a potential cancer therapy, for individuals with advanced cancers, specifically solid tumors or lymphoma, who lack other standard treatment options. The main goals are to assess the drug's safety, determine the optimal dose, and identify any early signs of effectiveness. Participants may include those with certain types of lymphoma, head and neck cancers, or cervical cancer that have either returned or not responded to previous treatments. Individuals with a type of cancer that fits these criteria might be suitable candidates for this trial. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot take certain treatments like chemotherapy, radiotherapy, or monoclonal antibodies within a specific time before starting the trial. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that ASTX660 is likely to be safe for humans?

Research has shown that ASTX660 has a manageable safety profile in several studies. In patients with peripheral T-cell lymphoma (PTCL) and cutaneous T-cell lymphoma (CTCL), ASTX660 has demonstrated promising results and is generally well-tolerated. Common side effects include tiredness and nausea, but these are usually not severe.

For head and neck squamous cell carcinoma (HNSCC), ASTX660 has been tested with other treatments and has shown potential effectiveness, with safety data supporting further research.

In diffuse large B-cell lymphoma (DLBCL), ASTX660 has shown early signs of effectiveness, though more detailed safety information is still being collected.

For cervical cancer, some patients experience long-term side effects, with about 15% having severe side effects.

Overall, ASTX660 is being tested to ensure safety and effectiveness. Studies suggest it is generally well-tolerated across different cancer types, though patients may experience side effects like tiredness or nausea. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about ASTX660 because it targets cancer cells differently from existing treatments. Unlike standard therapies for cancers like peripheral T-cell lymphoma and head and neck squamous cell carcinoma, which often involve chemotherapy or radiation, ASTX660 works by inhibiting specific proteins involved in cancer cell survival pathways, such as the NF-κB pathway. This targeted approach could potentially offer a more effective treatment, with fewer side effects than traditional methods. Moreover, ASTX660's ability to focus on molecular features specific to certain tumors makes it a promising candidate for personalized cancer therapy.

What evidence suggests that ASTX660 could be an effective treatment for cancer?

Research has shown that ASTX660 could help treat different types of cancer. In this trial, participants will receive ASTX660 for various conditions. For peripheral T-cell lymphoma (PTCL) and cutaneous T-cell lymphoma (CTCL), studies have found that ASTX660 works well and is generally safe. In head and neck squamous cell carcinoma (HNSCC), ASTX660 has been shown to help the immune system find and attack cancer cells. For diffuse large B-cell lymphoma (DLBCL), ASTX660 has shown promising results. Early studies for cervical cancer demonstrated that ASTX660, when used with other treatments, helped stop tumor growth and improved survival rates. Overall, ASTX660 targets specific proteins that help cancer cells survive, which might make it effective for various cancers. ^{1 6 7 8 9}

Who Is on the Research Team?

Jason Taylor, MD, PhD

Principal Investigator

Astex Pharmaceuticals, Inc.

Are You a Good Fit for This Trial?

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.

Inclusion Criteria

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

My lymphoma is CD30-positive and I can't use or have already used brentuximab vedotin.

I have mycosis fungoides or Sezary syndrome and cannot take mogamulizumab.

Exclusion Criteria

My brain metastases are stable or have been treated.

I have HIV or active hepatitis B or C.

I do not have severe nerve pain or damage.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1 - Dose Escalation

Dose-escalation stage to identify the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) using a 3+3 study design.

Up to 78 months

7 days on/7 days off every 28-day cycle

Phase 1 - Dose Expansion

Dose-expansion stage to confirm tolerability of ASTX660 at the RP2D.

Up to 78 months

Phase 2 - Treatment

Evaluation of ASTX660 activity in selected tumor types, including PTCL, HNSCC, DLBCL, CTCL, and cervical carcinoma.

Up to 84 months

Follow-up

Participants are monitored for safety and effectiveness after treatment.

Up to 84 months

What Are the Treatments Tested in This Trial?

Interventions

• ASTX660

Trial Overview 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.

How Is the Trial Designed?

Group I: Phase 2 - Cohort 6 Experimental Treatment 1 Intervention

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

Group II: Phase 2 - Cohort 5 Experimental Treatment 1 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 4 Experimental Treatment 1 Intervention

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

Group IV: Phase 2 - Cohort 3 Experimental Treatment 1 Intervention

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

Group V: Phase 2 - Cohort 2 Experimental Treatment 1 Intervention

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

Group VI: Phase 2 - Cohort 1 Experimental Treatment 1 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 Treatment 1 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 Treatment 1 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 Treatment 1 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.

Who Is Running the Clinical Trial?

Taiho Oncology, Inc.

Lead Sponsor

Trials

79

Recruited

12,700+

Tim Whitten

Taiho Oncology, Inc.

Chief Executive Officer since 2018

MBA and Pharmacy degree

Harold Keer

Taiho Oncology, Inc.

Chief Medical Officer

MD, PhD

Astex Pharmaceuticals, Inc.

Lead Sponsor

Trials

97

Recruited

7,400+

Dr. Harren Jhoti

Astex Pharmaceuticals, Inc.

Chief Executive Officer since 2007

PhD in Biochemistry from Birkbeck College, London

Dr. Harold N. Keer

Astex Pharmaceuticals, Inc.

Chief Medical Officer since 2020

MD

Published Research Related to This Trial

The study introduces five novel patient-derived ex vivo soft tissue sarcomas models that accurately represent the complex genetic makeup of these rare tumors, which can help in understanding their molecular pathogenesis and identifying new drug sensitivities.

These high-fidelity models are essential for improving patient stratification in functional precision oncology, particularly for soft tissue sarcomas, which are known for their heterogeneity and resistance to conventional treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Addressing Modern Diagnostic Pathology for Patient-Derived Soft Tissue Sarcosphere Models in the Era of Functional Precision Oncology. Chen, Y., Herzog, M., Pliego-Mendieta, A., et al.[2023]

A meta-analysis of 53 Phase II/III/IV trials involving nearly 20,000 patients revealed that molecular target anticancer drugs significantly increase the risk of serious adverse events (SAEs) by 57% and fatal adverse events (FAEs) by 51% compared to placebo.

The overall incidence rates for SAEs and FAEs were found to be 26.9% and 2.3%, respectively, highlighting the need for careful monitoring and preventive measures for patients receiving these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk of serious adverse event and fatal adverse event with molecular target anticancer drugs in cancer patients: A meta-analysis. Wang, Z., Yang, X., Wang, J., et al.[2020]

A review of 12 targeted anticancer drugs revealed that 39% of serious adverse drug reactions (ADRs) and 39% of potentially fatal ADRs were not reported in the corresponding pivotal randomized clinical trials (RCTs), highlighting a gap in safety information for oncologists.

After a median of 4.3 years post-approval, 42% of these drugs received boxed warnings from the FDA, indicating that significant safety concerns can emerge long after initial approval and may not be adequately addressed in early clinical trial reports.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reporting of serious adverse drug reactions of targeted anticancer agents in pivotal phase III clinical trials. Seruga, B., Sterling, L., Wang, L., et al.[2022]

A total of 3120 adverse event cases related to avapritinib were reported to the FDA, with 44% occurring within the first 30 days of treatment, highlighting the importance of monitoring patients closely during this period.

The study found that elderly male patients are at a higher risk for serious adverse events, indicating that clinicians should exercise caution when prescribing avapritinib to this demographic.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A post-marketing pharmacovigilance study of avapritinib: Adverse event data mining and analysis based on the United States Food and Drug Administration Adverse Event Reporting System database. Rong, L., Xie, M., Jiang, M., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11162013/

Dose escalation of tolinapant (ASTX660) in combination with ... Preclinical studies performed using tolinapant in combination with cisplatin and radiotherapy showed inhibition of tumour growth and enhanced survival.

2. astx.com astx.com/wp-content/uploads/2022/06/2022_ASTX660_Oral_EHA_abst-S217_Michot-final-website.pdf

preliminary analysis of the phase ii study using TOLINAPANT (ASTX660) MONOTHERAPY IN 98 PERIPHERAL T-. CELL LYMPHOMA AND 51 ... • Recent data demonstrates both apoptosis and immunomodulation. ‒ Phase 1 ...

3. aacrjournals.org aacrjournals.org/mct/article/18/12_Supplement/A072/240191/Abstract-A072-Preliminary-results-of-ASTX660-a

Abstract A072: Preliminary results of ASTX660, a novel non ... Here, we report overall efficacy and safety data from the solid tumors (head and neck squamous cell carcinoma [HNSCC]; cervical carcinoma and ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT02503423

NCT02503423 | Phase 1-2 Study of ASTX660 in Subjects ... This is an open-label, dose-escalation Phase 1/2 study to assess the safety of ASTX660, determine the maximum tolerated dose (MTD), recommended Phase 2 dose ...

5. mycancergenome.org mycancergenome.org/content/clinical_trials/NCT02503423/

Clinical Trial: NCT02503423 This is an open-label, dose-escalation Phase 1/2 study to assess the safety of ASTX660, determine the maximum tolerated dose (MTD), recommended ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6959437/

ASTX660, an antagonist of cIAP1/2 and XIAP, increases ... In this study, we show that ASTX660, an antagonist of cIAP1/2 and XIAP, induces expression of immunogenic cell death (ICD) markers in sensitive HNSCC cell ...

7. aacrjournals.org aacrjournals.org/clincancerres/article/26/12/2819/82562/A-Phase-I-Study-of-ASTX660-an-Antagonist-of

A Phase I Study of ASTX660, an Antagonist of Inhibitors of ... Overall, the most common AEs regardless of relationship to study treatment were fatigue (33%), vomiting (31%), and nausea (27%; Supplementary Table S2). The ...

8. onclive.com onclive.com/view/tolinapant-displays-encouraging-activity-and-safety-in-relapsed-refractory-ptcl-ctcl

Tolinapant Displays Encouraging Activity and Safety in ... Single-agent tolinapant (ASTX660) generated promising response rates with a manageable safety profile in patients with relapsed/refractory peripheral T-cell ...

9. trial.medpath.com trial.medpath.com/clinical-trial/914e8092a3a56997/2024-516679-33-00-astx660-advanced-solid-tumors-lymphomas

Study of the safety, activity, and effect on the body of ASTX660 ... ... ASTX660; # 6: Cervical carcinoma not responsive/relapsed after standard therapy ... ASTX660 if data permit; analysis of ASTX660 metabolites if applicable.