ASP2074 for Solid Tumors

Recruiting at 13 trial locations

Overseen By Astellas Pharma Global Development, Inc.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Astellas Pharma Global Development, Inc.

Must not be taking: Steroids, Immunosuppressants

Disqualifiers: CNS metastases, Active autoimmune, HIV, Hepatitis, Cardiovascular disease, others

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

Compensation: Varies

Number of Visits: 8

23 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a new drug called ASP2074 for adults with advanced cancers that have spread and no longer respond to standard treatments. The drug is given through an infusion, and the study will find the best dose and check for side effects. Patients will be closely monitored throughout the treatment.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, you cannot participate if you require systemic steroid therapy or other immunosuppressive therapy within 14 days before starting the study treatment, unless it's a low dose or for specific purposes like imaging contrast.

How does the drug ASP2074 differ from other treatments for solid tumors?

ASP2074 is unique because it may involve a novel mechanism of action or target specific pathways in solid tumors, potentially similar to how PARP inhibitors target DNA repair pathways. This could make it effective for tumors with specific genetic profiles, offering a new option where standard treatments are limited. ^{1 2 3 4 5}

Research Team

Senior Medical Director

Principal Investigator

Astellas Pharma Global Development, Inc.

Eligibility Criteria

Adults with advanced solid tumors that have spread and are not responding to standard treatments can join this trial. They must be in good physical condition (ECOG Status of 0 or 1), have recovered from previous therapies, agree to use contraception, and not be pregnant or breastfeeding. Specific cancers like colorectal, pancreatic, gastric cancer, esophageal or GEJ adenocarcinoma are included for certain parts of the study.

Inclusion Criteria

Participant must meet all of the criteria based on laboratory tests. In case of multiple laboratory data within this period, the most recent data should be used. If a participant has received a recent blood transfusion, the laboratory tests must be obtained >/= 2 weeks after any blood transfusion.

Participant has predicted life expectancy >/= 12 weeks.

I have at least one tumor that can be measured.

Exclusion Criteria

I have not had a stroke or mini-stroke in the last 6 months.

I have had major blood vessel problems, like an aneurysm or clot, in the last 6 months.

I haven't taken strong immune system suppressing drugs in the last 14 days, except for low-dose steroids or a one-time dose for tests.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation (Part 1)

Participants receive escalating doses of ASP2074 to determine suitable doses for Part 2

Up to 28 days per cycle

Multiple visits per cycle, with extra visits during the first 2 cycles

Dose Expansion (Part 2)

Participants receive ASP2074 at doses determined from Part 1 to find a more accurate dose for future studies

Up to 15 months

Regular visits during treatment cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 21 months

Clinic visits every 6 weeks, then calls every 12 weeks for up to 1 year

Treatment Details

Interventions

• ASP2074

Trial Overview ASP2074 is being tested as a new treatment for solid tumors. The trial has two parts: first to find safe doses by giving different amounts to small groups and monitoring for problems; second to confirm these doses in more people. It's given as an infusion at the start of each cycle until it's no longer tolerated or effective.

Participant Groups

Group I: ASP2074 Dose Expansion (Part 2) Pancreatic Adenocarcinoma Experimental Treatment 1 Intervention

Participants will receive ASP2074 with dose/regimen selected from dose escalation (Part 1).

Group II: ASP2074 Dose Expansion (Part 2) Esophageal or GEJ Adenocarcinoma Experimental Treatment 1 Intervention

Participants will receive ASP2074 with dose/regimen selected from dose escalation (Part 1).

Group III: ASP2074 Dose Expansion (Part 2) Colorectal Adenocarcinoma Experimental Treatment 1 Intervention

Participants will receive ASP2074 with dose/regimen selected from dose escalation (Part 1).

Group IV: ASP2074 Dose Escalation (Part 1) Experimental Treatment 1 Intervention

Participants will be assigned to sequentially or in parallel escalating dose/regimen cohorts of ASP2074 in three parts (Part A, B and C). Part B and Part C will be opened sequentially based upon sponsor review of emerging data.

Who Is Running the Clinical Trial?

Astellas Pharma Global Development, Inc.

Lead Sponsor

Trials

204

Recruited

123,000+

Tadaaki Taniguchi

Astellas Pharma Global Development, Inc.

Chief Medical Officer

M.D., Ph.D.

Naoki Okamura

Astellas Pharma Global Development, Inc.

Chief Executive Officer

Not available

Findings from Research

A new combination treatment strategy using the CDK4/6 inhibitor palbociclib shows promise for treating Rb-positive soft tissue sarcomas by inducing cell cycle arrest, making the cancer cells more sensitive to other treatments like doxorubicin.

This synergistic effect was confirmed in both laboratory tests and in vivo studies using patient-derived xenografts, providing strong preclinical support for future clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CDK4/6 Inhibitors Sensitize Rb-positive Sarcoma Cells to Wee1 Kinase Inhibition through Reversible Cell-Cycle Arrest. Francis, AM., Alexander, A., Liu, Y., et al.[2022]

A genomic analysis of 56 liposarcoma samples revealed that while there were few gene mutations, over half of the samples exhibited gene amplifications, particularly of MDM2, CDK4, and receptor tyrosine kinases (RTKs).

In laboratory tests, combining CDK4 and IGF1R inhibitors effectively suppressed the growth of a well-differentiated liposarcoma cell line with IGF1R amplification, suggesting that this combination therapy could be a promising treatment for patients with these tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Frequent amplification of receptor tyrosine kinase genes in welldifferentiated/ dedifferentiated liposarcoma. Asano, N., Yoshida, A., Mitani, S., et al.[2018]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Magnitude of benefit of the addition of poly ADP-ribose polymerase (PARP) inhibitors to therapy for malignant tumor: A meta-analysis. [2020]

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

CDK4/6 Inhibitors Sensitize Rb-positive Sarcoma Cells to Wee1 Kinase Inhibition through Reversible Cell-Cycle Arrest. [2022]

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

MCM4 Is a Novel Biomarker Associated With Genomic Instability, BRCAness Phenotype, and Therapeutic Potentials in Soft-Tissue Sarcoma. [2021]

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

Frequent amplification of receptor tyrosine kinase genes in welldifferentiated/ dedifferentiated liposarcoma. [2018]

5. United Arab Emirates pubmed.ncbi.nlm.nih.gov

The emerging role of poly(ADP-Ribose) polymerase inhibitors in cancer treatment. [2019]