NCT05593094|Active Not RecruitingPhase 1FDA Drug

A Phase 1 Trial of ZN-A-1041 Enteric Capsules or Combination in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Advanced Solid Tumors

A Phase 1 Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics (PK), and Efficacy of ZN-A-1041 Enteric Capsules as a Single Agent or in Combination in Patients With HER2-Positive Advanced Solid Tumors

Hoffmann-La Roche ClinicalTrials.gov

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3 other identifiers

XO45189ZN-A-1041-101-US2023-508459-37-00

Study Type

interventional

Target

210

Locations

7 countries

Sites

Timeline

RegisteredOct 2022

StartedSep 2020

CompletionAug 2027

Brief Summary

This will be a Phase 1, multicenter, open-label trial to evaluate the safety, tolerability, PK and efficacy of ZN-A-1041 as a monotherapy or in combination in participants with HER2-positive advanced solid tumors with or without brain metastases. The study will consist of three phases: Phase 1a (dose escalation with ZN-A-1041 monotherapy), Phase 1b (dose escalation with ZN-A-1041 combination therapy) and Phase 1c (dose expansion with ZN-A-1041 combination therapy).

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

210

participants targeted

Target at P75+ for phase_1

Timeline

15mo left

Started Sep 2020

Longer than P75 for phase_1

Geographic Reach

7 countries

36 active sites

Status

active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

7 years study duration

Study Progress83%

Sep 2020Aug 2027

Study Start

First participant enrolled

September 3, 2020

Completed

2.1 years until next milestone

First Submitted

Initial submission to the registry

October 17, 2022

Completed

8 days until next milestone

First Posted

Study publicly available on registry

October 25, 2022

Completed

4.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 31, 2027

Expected

Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

August 31, 2027

Last Updated

May 26, 2026

Status Verified

May 1, 2026

Enrollment Period

7 years

First QC Date

October 17, 2022

Last Update Submit

May 22, 2026

Conditions

Advanced Solid Tumors HER2-positive Breast Cancer

Keywords

Phase 1Advanced Solid TumorsHER2 postiveBrain metastasesHerceptinPerjetaPHESGOFirst Line1st Line

Outcome Measures

Primary Outcomes (3)

The Incidence of Treatment-emergent Adverse Events of ZN-A-1041 as a Monotherapy in Phase 1a
Dose at which no more than one out of six participant at the same dose level experiences a probable drug-related DLT.
23 days
The Incidence of Treatment-emergent Adverse Events of ZN-A-1041 in Combination with T-DM1 or with T-DXd, or in Combination with PHESGO or Herceptin plus Perjeta
Dose at which no more than one out of six participant at the same dose level experiences a probable drug-related DLT.
21 days
RP2D
To evaluate the safety of ZN-A-1041 in combination with T-DM1 or with T-DXd, or in combination with PHESGO or Herceptin plus Perjeta in participants on the RP2D.
Through study completion, an average of 1 year

Secondary Outcomes (5)

Plasma, Urine and Potentially Cerebrospinal Fluid (CSF) Level of ZN-A-1041 and its Main Metabolites
From baseline to cycle 9 (each cycel is 21 days)
Serum Level of Combination Drugs in Phase 1c
Through study completion, an average of 2 year
Anti-drug Antibodies (ADAs) Evaluation in Phase 1c
Through study completion, an average of 2 year
Overall Response Rate (ORR)
Through study completion, an average of 2 year
Progression Free Survival (PFS)
Through study completion, an average of 2 year

Study Arms (7)

1a: ZN-A-1041

EXPERIMENTAL

Phase 1a: Participants will receive escalating doses of ZN-A-1041 orally twice a day (BID) at pre-defined dosing regimens to determine the maximum tolerated dose (MTD).

Drug: ZN-A-1041

1b: ZN-A-1041 + T-DM1 3.6 mg/kg iv.

EXPERIMENTAL

Phase 1b Arm1: 1. If the maximum tolerated dose (MTD) of ZN-A-1041 is identified in Phase 1a study: The 2 tentative dose levels of ZN-A-1041 are MTD-1 (Level 1) and MTD (Level 2). 2. If the MTD is still not reached at the maximum dose level in Phase 1a study, the maximum dose level of ZN-A-1041 in Phase 1a will be used in Phase 1b study.

Drug: ZN-A-1041 + T-DM1 3.6 mg/kg iv. for Phase 1b

1b: ZN-A-1041 + T-Dxd 5.4 mg/kg iv.

EXPERIMENTAL

Phase 1b Arm2: 1. If the MTD of ZN-A-1041 is identified in Phase 1a study: The 2 tentative dose levels of ZN-A-1041 are MTD-1 (Level 1) and MTD (Level 2). 2. If the MTD is still not reached at the maximum dose level in Phase 1a study, the maximum dose level of ZN-A-1041 in Phase 1a will be used in Phase 1b study.

Drug: ZN-A-1041 + T-Dxd 5.4 mg/kg iv. for Phase 1b

1b: ZN-A-1041 + PHESGO / Herceptin plus Perjeta

EXPERIMENTAL

Phase 1b Arm3: 1. If the MTD of ZN-A-1041 is identified in Phase 1a study: The 2 tentative dose levels of ZN-A-1041 are MTD-1 (Level 1) and MTD (Level 2). 2. If the MTD is still not reached at the maximum dose level in Phase 1a study, the maximum dose level of ZN-A-1041 in Phase 1a will be used in Phase 1b study.

Drug: ZN-A-1041 + PHESGO / Herceptin plus Perjeta injection for Phase 1b

1c: ZN-A-1041 + T-DM1 3.6 mg/kg iv.

EXPERIMENTAL

Phase 1c Arm1: The recommended dose combination for Phase 1c will be determined by the Investigator and the Sponsor based on the data from Phase 1b.

Drug: ZN-A-1041 + T-DM1 3.6 mg/kg iv. for Phase 1c

1c: ZN-A-1041 + T-Dxd 5.4 mg/kg iv.

EXPERIMENTAL

Phase 1c Arm2: The recommended dose combination for Phase 1c will be determined by the Investigator and the Sponsor based on the data from Phase 1b.

Drug: ZN-A-1041 + T-Dxd 5.4 mg/kg iv. for Phase 1c

1c: ZN-A-1041 + Herceptin plus Perjeta/PHESGO

EXPERIMENTAL

Phase 1c Arm3: The recommended dose combination for Phase 1c will be determined by the Investigator and the Sponsor based on the data from Phase 1b.

Drug: ZN-A-1041 + PHESGO / Herceptin plus Perjeta injection for Phase 1c