ASTX660 for Cancer

Recruiting at 68 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

230 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

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.

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.

What safety data is available for ASTX660 in humans?

There is no specific safety data available for ASTX660 in the provided research articles. ^{1 2 3 4 5}

How is the drug ASTX660 unique for treating cancer?

ASTX660 is unique because it targets specific proteins involved in cancer cell survival, potentially offering a new approach for patients who do not respond to standard treatments like doxorubicin, which is often ineffective for certain cancers such as undifferentiated soft tissue sarcoma. ^{6 7 8 9 10}

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

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]

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]

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]

Citations

1. England 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. [2023]

2. India 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. [2020]

3. England pubmed.ncbi.nlm.nih.gov

The reporting of adverse events in oncology phase III trials: a comparison of the current status versus the expectations of the EORTC members. [2020]

4. Germany pubmed.ncbi.nlm.nih.gov

Safety Pharmacology of Anticancer Agents. [2015]

5. United States pubmed.ncbi.nlm.nih.gov

Reporting of serious adverse drug reactions of targeted anticancer agents in pivotal phase III clinical trials. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Patterns of sensitivity to a panel of drugs are highly individualised for undifferentiated/unclassified soft tissue sarcoma (USTS) in patient-derived orthotopic xenograft (PDOX) nude-mouse models. [2020]

7. United States pubmed.ncbi.nlm.nih.gov

Individualized doxorubicin sensitivity testing of undifferentiated soft tissue sarcoma (USTS) in a patient-derived orthotopic xenograft (PDOX) model demonstrates large differences between patients. [2020]

8. United States pubmed.ncbi.nlm.nih.gov

T-LAK cell-originated protein kinase (TOPK): an emerging prognostic biomarker and therapeutic target in osteosarcoma. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

P16 protein expression as a useful predictive biomarker for neoadjuvant chemotherapy response in patients with high-grade osteosarcoma: A systematic meta-analysis under guideline of PRISMA. [2021]

10. United States pubmed.ncbi.nlm.nih.gov

Addressing Modern Diagnostic Pathology for Patient-Derived Soft Tissue Sarcosphere Models in the Era of Functional Precision Oncology. [2023]