Advanced Solid TumorsPhase 1/2NCT05593094
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 1/2 study testing ZN-A-1041, ZN-A-1041 + T-DM1 3.6 mg/kg iv. for Phase 1b and ZN-A-1041 + T-Dxd 5.4 mg/kg iv. for Phase 1b in people with Advanced Solid Tumors and HER2-positive Breast Cancer, run by Hoffmann-La Roche at 36 sites in 7 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Solid Tumors, HER2-positive Breast Cancer
- What is being tested?
- ZN-A-1041, ZN-A-1041 + T-DM1 3.6 mg/kg iv. for Phase 1b and ZN-A-1041 + T-Dxd 5.4 mg/kg iv. for Phase 1b
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 210 participants
- Where
- 36 sitesin 7 countries
- Study dates
- 3 Sep 2020to 31 Aug 2027
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Life expectancy of at least 6 months, as determined by the investigator
- Histologically or cytologically confirmed with unresectable or metastatic HER2-positive advanced solid tumors
- Must be relapsed or refractory after prior treatment for metastatic disease that included a taxane and trastuzumab or must have received first-line induction therapy for advanced disease a pertuzumab plus trastuzumab-based regimen or a T-DXd-based regimen
- Participants with new, untreated, progressive, or stable brain metastases are eligible
Who cannot join
- Participation in any other clinical study involving an investigational drug or device within 4 weeks prior to the first dose of study treatment
- Any intracranial lesion (brain metastasis) that requires immediate local therapy, such as surgery or radiation, or systemic corticosteroids at the time of enrollment
Trial locations and contacts
36 sites in 7 countries.
36 sites in 7 countries
Spain13 sites
Hospital Universitario Ramon y Cajal
A Gudiña, Orense, 32540
Instituto de Investigacion Oncologica Vall dHebron (VHIO) - EPON
Argentona, Barcelona, 08310
Instituto Oncologico Dr. Rosell-Hospital Universitari Dexeus-Grupo Quironsalud
Barcelona, 08028
Hospital Clinic de Barcelona
Barcelona, 08036
Hospital Universitario de Jaen
Jaén, 23007
Hospital Universitario Virgen del Rocio
Las Cabezas de San Juan, Sevilla, 41730
Hospital Beata Maria Ana
Madrid, 28007
Hospital Clinico San Carlos
Madrid, 28040
Hospital Universitario 12 de Octubre
Madrid, 28041
Hospital Clinico Universitario de Santiago
Santiago de Compostela, LA Coruna, 15706
Hospital Universitario Virgen Macarena
Seville, 41009
Fundacion Instituto Valenciano de Oncologia (IVO)
Valencia, 46009
Hospital Clinico Universitario de Valencia
Valencia, 46010
United States8 sites
University of Michigan Hospital
Ann Arbor, Michigan, 48109
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
TOI Clinical Research
Cerritos, California, 90703-2684
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, 48201
Duke University School of Medicine
Durham, North Carolina, 27710
MD Anderson Cancer Center
Houston, Texas, 77030-4000
UCSF Helen Diller Family CCC
San Francisco, California, 94158
Arizona Clinical Research Center, Inc.;Hematology Oncology Physicians - Aoa
Tucson, Arizona, 85712
France7 sites
Centre Georges Francois Leclerc
Dijon, 21000
Centre Oscar Lambret
Lille, 59020
Centre Léon Bérard Centre Régional de Lutte Contre Le Cancer Rhône Alpes
Lyon, 69373
Institut Paoli-Calmettes
Marseille, 13009
Institut de Cancerologie de l Ouest
Saint-Herblain, 44805
EDOG - Institut Claudius Regaud - PPDS
Toulouse, Haute-Garonne, 31059
Gustave Roussy
Villejuif, 94800
Italy3 sites
Asst Papa Giovanni XXIII
Bergamo, Lombardy, 24127
Fondazione Policlinico Universitario A Gemelli-Rome
Magnago, Lombardy, 20020
Istituto Romagnolo per lo Studio dei Tumori Dino Amadori - IRST S.r.l - PPDS
Parma, Emilia-Romagna, 43126
Australia2 sites
Geelong Hospital
Geelong, Victoria, 3220
Sunshine Hospital
St Albans, Victoria, 3021
United Kingdom2 sites
Clatterbridge Cancer Centre
Liverpool, Merseyside, L69 3GL
The Christie
Manchester, Lancashire, M20 4BX
About this study
Official title: 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
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).
Read the detailed description
This study is composed of three parts designed to evaluate the safety and efficacy of ZN-A-1041 in participants with HER2-positive advanced solid tumors.
Phase 1a (Monotherapy Dose Escalation): In this first phase, participants will receive ZN-A-1041 alone. The study will begin with a low dose of ZN-A-1041, which will be gradually increased in new groups of participants to find the highest dose that can be given safely. This will establish the recommended dose for further study.
Phase 1b (Combination Dose Escalation): In the second phase, the study will evaluate the safety of giving ZN-A-1041 together with established standard-of-care therapies for HER2-positive breast cancer. Participants will be enrolled into one of three combination arms to receive ZN-A-1041 with either T-DM1, T-DXd, or a pertuzumab/trastuzumab-based regimen. This phase will identify the recommended dose for these combination therapies.
Phase 1c (Combination Dose Expansion): In the final phase, additional participants will be enrolled to receive ZN-A-1041 at the recommended combination doses identified in Phase 1b. This will allow for a more thorough evaluation of the safety and preliminary efficacy of these treatment regimens.
Throughout the study, participants will undergo screening, treatment, and follow-up periods to collect comprehensive data on the safety, tolerability, pharmacokinetics, and anti-tumor activity of ZN-A-1041, both as a single agent and in combination.
- Conditions
- Advanced Solid Tumors, HER2-positive Breast Cancer
- Being tested
- ZN-A-1041, ZN-A-1041 + T-DM1 3.6 mg/kg iv. for Phase 1b, ZN-A-1041 + T-Dxd 5.4 mg/kg iv. for Phase 1b, ZN-A-1041 + PHESGO / Herceptin plus Perjeta injection for Phase 1b, ZN-A-1041 + T-DM1 3.6 mg/kg iv. for Phase 1c
- Keywords
- Phase 1, Advanced Solid Tumors, HER2 postive, Brain metastases, Herceptin, Perjeta, PHESGO, First Line, 1st Line
- Medical subject headings
- Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ZN-A-1041Drug
Also called ZN-A-1041 Enteric Capsules
ZN-A-1041: escalating doses orally BID at pre-defined dosing regimens to determine the MTD
ZN-A-1041 + T-DM1 3.6 mg/kg iv. for Phase 1bDrug
Also called ZN-A-1041 Enteric Capsules
ZN-A-1041: BID via oral administration T-DM1: 3.6 mg/kg given as an intravenous infusion on the first day of each treatment cycle, once every 3 weeks (21-day cycle)
ZN-A-1041 + T-Dxd 5.4 mg/kg iv. for Phase 1bDrug
Also called ZN-A-1041 Enteric Capsules
ZN-A-1041: BID via oral administration T-DXd: 5.4 mg/kg given as an intravenous infusion on the first day of each treatment cycle, once every 3 weeks (21-day cycle)
ZN-A-1041 + PHESGO / Herceptin plus Perjeta injection for Phase 1bDrug
Also called ZN-A-1041 Enteric Capsules
ZN-A-1041: BID via oral administration PHESGO dose is 600 mg pertuzumab/600 mg trastuzumab/2000 unites hyaluronidase every 3 weeks for subcutaneous administrations (21-day cycle) Perjeta is 420 mg administered as an intravenous infusion Herceptin is 6 mg/kg administered as an intravenous infusion
ZN-A-1041 + T-DM1 3.6 mg/kg iv. for Phase 1cDrug
Also called ZN-A-1041 Enteric Capsules
ZN-A-1041: BID via oral administration T-DM1: intravenous infusion on the first day of each treatment cycle, once every 3 weeks (21-day cycle)
ZN-A-1041 + T-Dxd 5.4 mg/kg iv. for Phase 1cDrug
Also called ZN-A-1041 Enteric Capsules
ZN-A-1041: BID via oral administration T-DXd: intravenous infusion on the first day of each treatment cycle, once every 3 weeks (21-day cycle)
ZN-A-1041 + PHESGO / Herceptin plus Perjeta injection for Phase 1cDrug
Also called ZN-A-1041 Enteric Capsules
ZN-A-1041: BID via oral administration PHESGO: every 3 weeks for subcutaneous administrations (21-day cycle) Perjeta: intravenous infusion Herceptin: intravenous infusion
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: Drug: ZN-A-1041 + PHESGO / Herceptin plus Perjeta injection for Phase 1c |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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
To assess the PK of ZN-A-1041 and its major metabolites.
Measured: From baseline to cycle 9 (each cycel is 21 days)
Serum Level of Combination Drugs in Phase 1c
To assess the serum concentration of combination drugs.
Measured: Through study completion, an average of 2 year
Anti-drug Antibodies (ADAs) Evaluation in Phase 1c
To assess the incidence of ADAs.
Measured: Through study completion, an average of 2 year
Overall Response Rate (ORR)
The preliminary efficacy of ZN-A-1041 as a monotherapy or combination in Phase 1a, Phase 1b and 1c.
Measured: Through study completion, an average of 2 year
Progression Free Survival (PFS)
The preliminary efficacy of ZN-A-1041 as a monotherapy or combination in Phase 1a, Phase 1b and 1c.
Measured: Through study completion, an average of 2 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Oct 2022
- Study start3 Sep 2020
- Primary completion31 Aug 2027 (estimated)
- Study completion31 Aug 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Solid TumorsStudies of the same condition, open and under way.
- More trials run by Hoffmann-La RocheThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 210 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05593094
- Sponsor's protocol ID
- XO45189
- Other IDs
- ZN-A-1041-101-US, 2023-508459-37-00, 2023
- Status last verified
- Aug 2026
- First submitted
- 17 Oct 2022
- Last updated
- 21 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data\_sharing
Study at a glance
From the registry record, last updated by the sponsor on 21 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT05593094
- Acronym / sponsor ID
- XO45189
- Conditions
- Advanced Solid Tumors, HER2-positive Breast Cancer
- Keywords
- Phase 1, Advanced Solid Tumors, HER2 postive, Brain metastases, Herceptin, Perjeta, PHESGO, First Line
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 210 participants (estimated)
- Lead sponsor
- Hoffmann-La RocheIndustry (pharma, biotech, devices)
- Study start
- 3 Sep 2020 (actual)
- Primary completion
- 31 Aug 2027 (estimated)
- Study completion
- 31 Aug 2027 (estimated)
- First posted
- 25 Oct 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
This study is composed of three parts designed to evaluate the safety and efficacy of ZN-A-1041 in participants with HER2-positive advanced solid tumors.
Phase 1a (Monotherapy Dose Escalation): In this first phase, participants will receive ZN-A-1041 alone. The study will begin with a low dose of ZN-A-1041, which will be gradually increased in new groups of participants to find the highest dose that can be given safely. This will establish the recommended dose for further study.
Phase 1b (Combination Dose Escalation): In the second phase, the study will evaluate the safety of giving ZN-A-1041 together with established standard-of-care therapies for HER2-positive breast cancer. Participants will be enrolled into one of three combination arms to receive ZN-A-1041 with either T-DM1, T-DXd, or a pertuzumab/trastuzumab-based regimen. This phase will identify the recommended dose for these combination therapies.
Phase 1c (Combination Dose Expansion): In the final phase, additional participants will be enrolled to receive ZN-A-1041 at the recommended combination doses identified in Phase 1b. This will allow for a more thorough evaluation of the safety and preliminary efficacy of these treatment regimens.
Throughout the study, participants will undergo screening, treatment, and follow-up periods to collect comprehensive data on the safety, tolerability, pharmacokinetics, and anti-tumor activity of ZN-A-1041, both as a single agent and in combination.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 7
| Arm | Type | Receives |
|---|---|---|
| 1a: ZN-A-1041 | Experimental | Drug: ZN-A-1041Phase 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). |
| 1b: ZN-A-1041 + T-DM1 3.6 mg/kg iv. | Experimental | Drug: ZN-A-1041 + T-DM1 3.6 mg/kg iv. for Phase 1bPhase 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. |
| 1b: ZN-A-1041 + T-Dxd 5.4 mg/kg iv. | Experimental | Drug: ZN-A-1041 + T-Dxd 5.4 mg/kg iv. for Phase 1bPhase 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. |
| 1b: ZN-A-1041 + PHESGO / Herceptin plus Perjeta | Experimental | Drug: ZN-A-1041 + PHESGO / Herceptin plus Perjeta injection for Phase 1bPhase 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. |
| 1c: ZN-A-1041 + T-DM1 3.6 mg/kg iv. | Experimental | Drug: ZN-A-1041 + T-DM1 3.6 mg/kg iv. for Phase 1cPhase 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. |
| 1c: ZN-A-1041 + T-Dxd 5.4 mg/kg iv. | Experimental | Drug: ZN-A-1041 + T-Dxd 5.4 mg/kg iv. for Phase 1cPhase 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. |
| 1c: ZN-A-1041 + Herceptin plus Perjeta/PHESGO | Experimental | Drug: ZN-A-1041 + PHESGO / Herceptin plus Perjeta injection for Phase 1cPhase 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Life expectancy of at least 6 months, as determined by the investigator
- Histologically or cytologically confirmed with unresectable or metastatic HER2-positive advanced solid tumors
- Must be relapsed or refractory after prior treatment for metastatic disease that included a taxane and trastuzumab or must have received first-line induction therapy for advanced disease a pertuzumab plus trastuzumab-based regimen or a T-DXd-based regimen
- Participants with new, untreated, progressive, or stable brain metastases are eligible
Key exclusion criteria (2 listed)
- Participation in any other clinical study involving an investigational drug or device within 4 weeks prior to the first dose of study treatment
- Any intracranial lesion (brain metastasis) that requires immediate local therapy, such as surgery or radiation, or systemic corticosteroids at the time of enrollment
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ZN-A-1041Also: ZN-A-1041 Enteric CapsulesZN-A-1041: escalating doses orally BID at pre-defined dosing regimens to determine the MTD | Drug | 1a: ZN-A-1041 |
| ZN-A-1041 + T-DM1 3.6 mg/kg iv. for Phase 1bAlso: ZN-A-1041 Enteric CapsulesZN-A-1041: BID via oral administration T-DM1: 3.6 mg/kg given as an intravenous infusion on the first day of each treatment cycle, once every 3 weeks (21-day cycle) | Drug | 1b: ZN-A-1041 + T-DM1 3.6 mg/kg iv. |
| ZN-A-1041 + T-Dxd 5.4 mg/kg iv. for Phase 1bAlso: ZN-A-1041 Enteric CapsulesZN-A-1041: BID via oral administration T-DXd: 5.4 mg/kg given as an intravenous infusion on the first day of each treatment cycle, once every 3 weeks (21-day cycle) | Drug | 1b: ZN-A-1041 + T-Dxd 5.4 mg/kg iv. |
| ZN-A-1041 + PHESGO / Herceptin plus Perjeta injection for Phase 1bAlso: ZN-A-1041 Enteric CapsulesZN-A-1041: BID via oral administration PHESGO dose is 600 mg pertuzumab/600 mg trastuzumab/2000 unites hyaluronidase every 3 weeks for subcutaneous administrations (21-day cycle) Perjeta is 420 mg administered as an intravenous infusion Herceptin is 6 mg/kg administered as an intravenous infusion | Drug | 1b: ZN-A-1041 + PHESGO / Herceptin plus Perjeta |
| ZN-A-1041 + T-DM1 3.6 mg/kg iv. for Phase 1cAlso: ZN-A-1041 Enteric CapsulesZN-A-1041: BID via oral administration T-DM1: intravenous infusion on the first day of each treatment cycle, once every 3 weeks (21-day cycle) | Drug | 1c: ZN-A-1041 + T-DM1 3.6 mg/kg iv. |
| ZN-A-1041 + T-Dxd 5.4 mg/kg iv. for Phase 1cAlso: ZN-A-1041 Enteric CapsulesZN-A-1041: BID via oral administration T-DXd: intravenous infusion on the first day of each treatment cycle, once every 3 weeks (21-day cycle) | Drug | 1c: ZN-A-1041 + T-Dxd 5.4 mg/kg iv. |
| ZN-A-1041 + PHESGO / Herceptin plus Perjeta injection for Phase 1cAlso: ZN-A-1041 Enteric CapsulesZN-A-1041: BID via oral administration PHESGO: every 3 weeks for subcutaneous administrations (21-day cycle) Perjeta: intravenous infusion Herceptin: intravenous infusion | Drug | 1c: ZN-A-1041 + Herceptin plus Perjeta/PHESGO |
Primary outcome
The Incidence of Treatment-emergent Adverse Events of ZN-A-1041 as a Monotherapy in Phase 1a
Time frame: 23 days
Dose at which no more than one out of six participant at the same dose level experiences a probable drug-related DLT.
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
Time frame: 21 days
Dose at which no more than one out of six participant at the same dose level experiences a probable drug-related DLT.
RP2D
Time frame: Through study completion, an average of 1 year
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.
5 secondary outcomes
Plasma, Urine and Potentially Cerebrospinal Fluid (CSF) Level of ZN-A-1041 and its Main Metabolites
Time frame: From baseline to cycle 9 (each cycel is 21 days)
Serum Level of Combination Drugs in Phase 1c
Time frame: Through study completion, an average of 2 year
Anti-drug Antibodies (ADAs) Evaluation in Phase 1c
Time frame: Through study completion, an average of 2 year
Overall Response Rate (ORR)
Time frame: Through study completion, an average of 2 year
Progression Free Survival (PFS)
Time frame: Through study completion, an average of 2 year
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Aug 2026.
- Individual participant dataSharing planned: Yes. For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data_sharing
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Active, not recruitingPhase 1
A Study to Assess Safety, Tolerability, and Pharmacokinetics of ABSK043 in Patients With Advanced Solid Tumor
Neoplasms
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A Study of Neladalkib (NVL-655) in Patients With Advanced NSCLC and Other Solid Tumors Harboring ALK Rearrangement or Activating ALK Mutation (ALKOVE-1)
Locally Advanced Solid Tumor, Metastatic Solid Tumor
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Testing AZD5363 as a Potential Targeted Treatment in Cancers With AKT Genetic Changes (MATCH-Subprotocol Y)
Advanced Lymphoma, Advanced Malignant Solid Neoplasm
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Docetaxel and SX-682 in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma, Salivary Gland Carcinoma, and Advanced Prostate Cancer
Head and Neck Cancer, Head and Neck Squamous Cell Carcinoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Trials study director
Hoffmann-La Roche
36 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing ZN-A-1041, ZN-A-1041 + T-DM1 3.6 mg/kg iv. for Phase 1b and ZN-A-1041 + T-Dxd 5.4 mg/kg iv. for Phase 1b in people with Advanced Solid Tumors and HER2-positive Breast Cancer, run by Hoffmann-La Roche at 36 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 21 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 36 sites in Spain, United States, France, Italy, Australia and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The Incidence of Treatment-emergent Adverse Events of ZN-A-1041 as a Monotherapy in Phase 1a (time frame: 23 days). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Aug 2026.