ASTX295 for Solid Cancers

No longer 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called ASTX295 for individuals with advanced solid tumors. It aims to determine the treatment's safety, behavior in the body, and initial effectiveness. The trial seeks participants with wild-type TP53 tumors that have not responded to other treatments or for whom no standard treatment options exist. Suitable candidates include those with certain advanced cancers that cannot be surgically removed and have not responded to previous therapies. As a Phase 1 trial, this research focuses on understanding how ASTX295 works in people, offering participants the opportunity to be among the first to receive this new treatment.

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.

Is there any evidence suggesting that ASTX295 is likely to be safe for humans?

Research is investigating the safety of ASTX295 for treating solid tumors with a specific gene type. Early studies have shown that the main side effects are stomach-related, such as nausea and vomiting, rather than affecting blood cells. As doses increased, more stomach-related side effects appeared. Detailed safety information from this study is not yet available because the treatment remains in early testing. Researchers are primarily determining its safety and the appropriate dosage. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about ASTX295 because it targets a specific protein called MDM2, which plays a role in the growth of solid tumors. Unlike standard treatments that may target the tumor itself, ASTX295 aims to reactivate the body's natural tumor suppressor, p53, by inhibiting MDM2. This approach could offer a more targeted and potentially less toxic alternative to traditional chemotherapy options. By focusing on this novel mechanism, ASTX295 holds promise for effectively treating solid cancers in a new way.

What evidence suggests that ASTX295 might be an effective treatment for advanced solid tumors?

Research has shown that ASTX295, the investigational treatment in this trial, targets a protein called MDM2, which helps fight cancer by activating another protein, p53. Often referred to as the "guardian of the genome," p53 controls cell growth and can stop cancer cells from spreading. In studies with patients who have solid tumors with a specific type of TP53 gene, ASTX295 was well tolerated and showed promising results in affecting the p53 pathway. This suggests it could potentially control tumor growth without causing major side effects. These early findings indicate that ASTX295 could be an effective option for treating solid tumors with this genetic profile. ^{1 2 3 6 7}

Who Is on the Research Team?

Kim-Hein Dao, DO, PhD

Principal Investigator

Astex Pharmaceuticals, Inc.

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

Citations

1. astx.com astx.com/wp-content/uploads/2024/04/Phase-1-study-of-MDM2-antagonist-ASTX295-in-patients-with-solid-tumors-with-wild-type-TP53.pdf

Phase-1-study-of-MDM2-antagonist-ASTX295-in-patients- ... Phase 1 study of MDM2 antagonist ASTX295 in patients with solid tumors with wild-type TP53 ... ASTX295 was well tolerated at clinically effective ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03975387

Study of ASTX295 in Patients With Solid Tumors With Wild- ... Study ASTX295-01 is a first in human Phase 1/2 open-label study of the safety, pharmacokinetics, and preliminary activity of ASTX295 in participants with ...

3. aacrjournals.org aacrjournals.org/cancerres/article/84/7_Supplement/CT066/742337/Abstract-CT066-Phase-1-study-of-MDM2-antagonist

Abstract CT066: Phase 1 study of MDM2 antagonist ASTX295 ... Conclusion:ASTX295 was well tolerated at doses producing p53 pathway modulation with manageable toxicities, notably avoiding significant ...

4. delveinsight.com delveinsight.com/blog/astx295-phase-i-study-result

ASTX295 Phase 1 Study Result | AACR 2024 ASTX295 was well tolerated at doses producing p53 pathway modulation with manageable toxicities, notably avoiding significant thrombocytopenia.

5. cancerresearchhorizons.com cancerresearchhorizons.com/news-and-events/our-news/collaborative-discovery-yields-promising-results-novel-mdm2-p53-antagonist

Collaborative discovery yields promising results in novel ... ASTX295 distinguishes itself from other MDM2-p53 antagonists with its shorter plasma half-life, resulting in a potentially broader therapeutic window and ...

6. withpower.com withpower.com/trial/phase-2-neoplasms-6-2019-0dc60

ASTX295 for Solid Cancers · Info for Participants What safety data exists for ASTX295 in humans? The research articles reviewed do not provide specific safety data for ASTX295. However, they discuss general ...

7. clinicaltrialsregister.eu clinicaltrialsregister.eu/ctr-search/trial/2021-005033-16/DE

Clinical Trials Register To characterize the safety profile of ASTX295. • To determine the PK profile of ASTX295. • To evaluate other parameters of clinical activity.