RecruitingPhase 1

Testing the Combination of the Anticancer Drugs Trastuzumab Deruxtecan (DS-8201a) and Azenosertib (ZN-c3) in Patients With Stomach or Other Solid Tumors

United States48 participantsStarted 2025-02-03

Plain-language summary

This phase I trial tests the safety, side effects, and best dose of azenosertib in combination with trastuzumab deruxtecan in treating patients with HER2-positive gastric or gastroesophageal junction cancer and other HER2-positive solid tumors that have spread to nearby tissue or lymph nodes (locally advanced), that have spread from where it first started (primary site) to other places in the body (metastatic), or that cannot be removed by surgery (unresectable). Azenosertib is in a class of medications called kinase inhibitors. It inhibits a protein called Wee1. Inhibition of the Wee1 protein can make tumor cells more vulnerable to chemotherapy drugs, leading to tumor cell death. Trastuzumab deruxtecan is in a class of medications called antibody-drug conjugates. It is composed of a monoclonal antibody, called trastuzumab, linked to a chemotherapy drug, called deruxtecan. Trastuzumab attaches to HER2 positive cancer cells in a targeted way and delivers deruxtecan to kill them. Giving azenosertib in combination with trastuzumab deruxtecan may be safe, tolerable, and/or more effective in treating patients with locally advanced, metastatic, or unresectable HER2-positive gastric, gastroesophageal junction, or other solid tumors, compared to just trastuzumab deruxtecan alone.

Who can participate

Age range

18 Years

Sex

ALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Inclusion Criteria: * In the dose escalation, patients must have a histologically documented locally advanced, unresectable, or metastatic solid tumor that has progressed following at least one prior line of treatment in the metastatic setting or has no satisfactory alternative treatment option and all of the following: * HER2 expression by immunohistochemistry (IHC) (1+, 2+, or 3+) or HER2 amplification by in situ hybridization (ISH) or next generation sequencing (NGS) (on any Clinical Laboratory Improvements Amendments \[CLIA\] platform on tissue), AND * T-DXd (DS-8201a)-naive disease * In the dose expansion, patients must have histologically documented locally advanced, unresectable or metastatic gastric or gastroesophageal junction (GEJ) cancer that has progressed following at least one prior line of treatment in the metastatic setting and have all of the following: * HER2 expression by IHC (1+, 2+, or 3+) or HER2 amplification by ISH or NGS (on any CLIA platform on tissue), AND * T-DXd (DS-8201a)-naive disease * Received prior trastuzumab-based treatment, if eligible for such treatment * For the dose escalation and dose expansion, patients can have evaluable or measurable disease * Potential trial participants should have recovered from clinically significant adverse events (AEs) of their most recent therapy/intervention prior to enrollment * Age ≥ 18 years. Because no dosing or AE data are currently available on the use of T-DXd (DS-8201a) in combination wi…

Questions worth asking your doctor

Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.

1Based on my diagnosis and history, is this trial worth exploring for me — or is there a standard treatment we should try first?
2What does this trial's phase tell us about how much is already known about its safety and benefit?
3What would taking part actually involve for me — visits, tests, time, and travel?
4What are the known and possible risks or side effects I should weigh, and how would they be monitored?
5If this trial isn't the right fit, what other options or trials would you suggest I look into?

Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.

Questions for the trial coordinator

The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.

1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?

A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.

What they're measuring

Maximum tolerated dose

Timeframe: Up to completion of dose-escalation

Recommended phase 2 dose

Timeframe: Up to completion of dose-escalation

Incidence of dose limiting toxicities (DLTs)

Timeframe: Up to completion of dose-escalation

Incidence of adverse events (AEs)

Timeframe: Up to 30 days after the last administration of study intervention

Trial details

NCT IDNCT06364410

SponsorNational Cancer Institute (NCI)

Sponsor typeNIH

Study typeINTERVENTIONAL

Primary completion2027-07-08

View on ClinicalTrials.gov More Clinical Stage III Gastric Cancer AJCC v8 trials

Plain-language summary

Who can participate

Age range

18 Years

Sex

ALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

What they're measuring

Maximum tolerated dose

Timeframe: Up to completion of dose-escalation

Recommended phase 2 dose

Timeframe: Up to completion of dose-escalation

Incidence of dose limiting toxicities (DLTs)

Timeframe: Up to completion of dose-escalation

Incidence of adverse events (AEs)

Timeframe: Up to 30 days after the last administration of study intervention