ASTX295 for Solid Cancers

Recruiting at 29 trial locations

Overseen By Astex Pharmaceuticals

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Taiho Oncology, Inc.

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: Unknown

106 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug called ASTX295 in patients with advanced solid tumors who have a normal TP53 gene. The study aims to find out if the drug is safe and how it behaves in the body. Researchers want to see if it can help treat cancer without causing harmful side effects.

Will I have to stop taking my current medications?

The trial requires that you stop certain anticancer treatments before starting the study drug. Specifically, you must stop cytotoxic chemotherapy 3 weeks prior, monoclonal antibodies or immunotherapy 4 weeks prior, and other investigational drugs 4 weeks or 5 half-lives prior, whichever is shorter.

What safety data exists for ASTX295 in humans?

The research articles reviewed do not provide specific safety data for ASTX295. However, they discuss general safety concerns related to targeted therapies and immunotherapies, such as skin, stomach, lung, and heart issues, which are usually mild and manageable if treated early. ^{1 2 3 4 5}

Research Team

Kim-Hein Dao, DO, PhD

Principal Investigator

Astex Pharmaceuticals, Inc.

Eligibility Criteria

Adults with advanced solid tumors that have not spread and are untreatable or have returned after standard therapy. They must be in fairly good health, able to perform daily activities (ECOG 0-2), and have normal organ function tests. Specific tumor types are eligible for different phases of the trial, all requiring a wild-type TP53 gene.

Inclusion Criteria

My cancer type matches one of the specific categories listed for the trial.

Serum total bilirubin ≤1.5 × upper limit of normal (ULN).

My cancer has spread, cannot be surgically removed, and does not respond to standard treatments.

Exclusion Criteria

My heart's pumping ability is below normal.

Screening 12-lead electrocardiogram (ECG) with measurable QTcF interval of ≥470 msec. (Fridericia's formula should be used).

I have advanced HIV or AIDS.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1: Dose Escalation and Expansion

Participants receive ASTX295 to determine the recommended Phase 2 dose and assess preliminary clinical activity

6 months to 1 year

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• ASTX295

Trial Overview ASTX295 is being tested in patients with specific solid tumors containing the wild-type TP53 gene. The study has two parts: Phase 1 to find the right dose and see how safe it is, followed by Phase 2 to check its effectiveness against certain cancers.

Participant Groups

Group I: ASTX295 Experimental Treatment 1 Intervention

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

Findings from Research

A review of 81 clinical trials involving over 45,000 patients revealed that the reporting of adverse events (AEs) for targeted therapies and immunotherapies is often inadequate, particularly regarding recurrent/late toxicities and the duration of AEs.

The study highlights that more than 90% of trials failed to adequately report the timing and occurrence of all-grade AEs, indicating a need for improved transparency and detail in AE reporting in future oncology trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic Review of adverse events reporting in clinical trials leading to approval of targeted therapy and immunotherapy. Bossi, P., Botta, L., Bironzo, P., et al.[2020]

Targeted therapies for non-small cell lung cancer (NSCLC) have significantly improved treatment options, but their effectiveness can be compromised by issues like poor patient adherence and adverse events.

The review highlights the need for standardized monitoring protocols for the various toxicities associated with these therapies, which can include skin, gastrointestinal, lung, and heart-related side effects, to ensure better patient management and treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted Toxicities: Protocols for Monitoring the Adverse Events of Targeted Therapies Used in the Treatment of Non-Small Cell Lung Cancer. Hines, JB., Bowar, B., Levine, E., et al.[2023]

Adjuvant therapy with PD-1/PD-L1 inhibitors significantly improves overall survival (OS) and disease-free survival (DFS) in cancer patients, based on a meta-analysis of six randomized controlled trials involving 4,436 participants.

While these treatments offer substantial survival benefits, they are also associated with a higher risk of severe treatment-related adverse events (≥ grade 3), indicating a need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of adjuvant therapy with PD‑1/PD‑L1 inhibitors in cancer. Mo, DC., Liang, ZY., Chen, L., et al.[2022]

The maximum tolerated dose (MTD) of sunitinib combined with pemetrexed and cisplatin was determined to be 37.5 mg of sunitinib, 500 mg/m² of pemetrexed, and 75 mg/m² of cisplatin on a 2 weeks on, 1 week off schedule, but this regimen was associated with significant cumulative myelosuppression, requiring dose reductions.

Despite the challenges with tolerability, the treatment showed modest antitumor activity, with 50% of evaluable patients with non-small cell lung cancer achieving stable disease for at least 8 weeks, and one patient with mesothelioma experiencing a partial response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sunitinib combined with pemetrexed and cisplatin: results of a phase I dose-escalation and pharmacokinetic study in patients with advanced solid malignancies, with an expanded cohort in non-small cell lung cancer and mesothelioma. Camidge, DR., Blais, N., Jonker, DJ., et al.[2018]

References

1. England pubmed.ncbi.nlm.nih.gov

Systematic Review of adverse events reporting in clinical trials leading to approval of targeted therapy and immunotherapy. [2020]

2. France pubmed.ncbi.nlm.nih.gov

Immune Checkpoint Blockade: The New Frontier in Cancer Treatment. [2019]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Targeted Toxicities: Protocols for Monitoring the Adverse Events of Targeted Therapies Used in the Treatment of Non-Small Cell Lung Cancer. [2023]

4. Greece pubmed.ncbi.nlm.nih.gov

Efficacy and safety of adjuvant therapy with PD‑1/PD‑L1 inhibitors in cancer. [2022]

5. Germany pubmed.ncbi.nlm.nih.gov

Sunitinib combined with pemetrexed and cisplatin: results of a phase I dose-escalation and pharmacokinetic study in patients with advanced solid malignancies, with an expanded cohort in non-small cell lung cancer and mesothelioma. [2018]