Trial of ZN-A-1041 Enteric Capsules in Patients With HER2-Positive Advanced Solid Tumors

NCT04487236 | Completed Phase 1

• 1 other identifier: ZN-A-1041-101
• Study Type: interventional
• Target: 61
• Locations: 1 country
• Sites: 1

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 patients with HER2-positive advanced solid tumors. The study will consist of three phases: phase 1a (dose escalation with ZN-A-1041 monotherapy), phase 1b (dose escalation with ZN-A-1041 in combination with Capecitabine and Trastuzumab) and phase 1c (dose expansion with ZN-A-1041 in combination with Capecitabine and Trastuzumab).

Conditions

Advanced Solid Tumors; HER2-positive Breast Cancer

Keywords

Phase 1; Advanced Solid Tumors; HER2-Positive Breast Cancer; Brain metastases

Outcome Measures

Primary Outcomes (3)

• The safety/tolerability of ZN-A-1041 as a monotherapy on Phase 1a

  Dose at which no more than one out of six patient at the same dose level experiences a probable drug-related dose limiting toxicity.

  23days

• The safety/tolerability of ZN-A-1041 in combination with Capecitabine and Trastuzumab in Phase 1b

  Dose at which no more than one out of six patient at the same dose level experiences a probable drug-related dose limiting toxicity.

  21days

• The safety of ZN-A-1041 in combination with Capecitabine and Trastuzumab in Phase 1c

  To evaluate the safety of ZN-A-1041 in combination with Capecitabine in patients on the RP2D Dose

  through study completion, an average of 3 year

Secondary Outcomes (4)

• Plasma Level of ZN-A-1041 and its major metabolites on phase 1a,phase 1b and 1c

  From baseline to Day 8

• Plasma Level of ZN-A-1041 and its major metabolites on Phase 1a,phase 1 b and 1c

  From baseline to Day 8

• Plasma level of ZN-A-1041 and its main metabolites Phase 1a,phase 1b and 1c

  From baseline to Day 8

• The preliminary efficacy of ZN-A-1041 as a monotherapy or combination in Phase 1a,phase 1b and 1c

  through study completion, an average of 3 year

Study Arms (11)

ZN-A-1041 50mg

EXPERIMENTAL

Phase 1a: Subjects will be given ZN-A-1041 orally 50mg Bid, for 21days as one cycle

Drug: ZN-A-1041 50mg BID

ZN-A-1041 100mg

EXPERIMENTAL

Phase 1a: Subjects will be given ZN-A-1041 orally 100mg Bid, for 21days as one cycle

Drug: ZN-A-1041 100mg BID

ZN-A-1041 200mg

EXPERIMENTAL

Phase 1a: Subjects will be given ZN-A-1041 orally 200mg Bid, for 21days as one cycle

Drug: ZN-A-1041 200mg BID

ZN-A-1041 400mg

EXPERIMENTAL

Phase 1a: Subjects will be given ZN-A-1041 orally 400mg Bid, for 21days as one cycle

Drug: ZN-A-1041 400mg BID

ZN-A-1041 600mg

EXPERIMENTAL

Phase 1a: Subjects will be given ZN-A-1041 orally 600mg Bid, for 21days as one cycle

Drug: ZN-A-1041 600mg BID

ZN-A-1041 800mg

EXPERIMENTAL

Phase 1a: Subjects will be given ZN-A-1041 orally 800mg Bid, for 21days as one cycle

Drug: ZN-A-1041 800mg BID

ZN-A-1041 1000mg

EXPERIMENTAL

Phase 1a: Subjects will be given ZN-A-1041 orally 1000mg Bid, for 21days as one cycle

Drug: ZN-A-1041 1000mg BID

ZN-A-1041 level 1+Capecitabine 1000 mg/m2 + Trastuzumab 8 mg/kg iv. First Cycle

EXPERIMENTAL

Phase 1b: ZN-A-1041 Level 1 (The previous dose of MTD) to be used in the combination therapy will be determined based on the MTD identified in the Phase 1a study. Capecitabine will be given at the dose of 1000 mg/m2, BID (2000 mg/m2/day), during the first 2 weeks of the 21-day treatment cycle. Trastuzumab (8 mg/kg in cycle 1 followed by 6 mg/kg beginning in cycle 2, administered as an IV infusion. If intolerance, reduce Capecitabine dose to 750 mg/m2 for exploration

Drug: ZN-A-1041 Level 1 +Capecitabine 1000 mg/m2 + Trastuzumab 8 mg/kg iv. First Cycle

ZN-A-1041 level 2+Capecitabine 1000 mg/m2+ Trastuzumab 8 mg/kg iv. First Cycle

EXPERIMENTAL

Phase 1b: ZN-A-1041 Level 2 ( dose of MTD) to be used in the combination therapy will be determined based on the MTD identified in the Phase 1a study. Capecitabine will be given at the dose of 1000 mg/m2, BID (2000 mg/m2/day), during the first 2 weeks of the 21-day treatment cycle. Trastuzumab (8 mg/kg in cycle 1 followed by 6 mg/kg beginning in cycle 2, administered as an IV infusion. If intolerance, reduce Capecitabine dose to 750 mg/m2 for exploration

Drug: ZN-A-1041 Level 2 +Capecitabine 1000 mg/m2 + Trastuzumab 8 mg/kg iv. First Cycle

ZN-A-1041 MAD+Capecitabine 1000 mg/m2+Trastuzumab 8 mg/kg iv. First Cycle

EXPERIMENTAL

Phase 1b: If the MTD is still not reached at the maximum dose level in Phase 1a study, the maximum dose level (MAD) of ZN-A-1041 in Phase 1a will be used in Phase 1b study. If intolerance, reduce Capecitabine dose to 750 mg/m2 for exploration

Drug: ZN-A-1041 MAD +Capecitabine 1000 mg/m2 + Trastuzumab 8 mg/kg iv. First Cycle

ZN-A-1041+Capecitabine+Trastuzumab

EXPERIMENTAL

Phase 1c: The combined dose of ZN-A-1041 is based on the recommended combined dose in the Phase 1b and the possible changes in the dosage form and the results of the food effect study, which will be decided by the sponsor and the investigator after discussion

Drug: ZN-A-1041+Capecitabine + Trastuzumab 8 mg/kg iv. First Cycle

Interventions

ZN-A-1041 50mg BID DRUG

Orally 21days for one cycle

Also known as: ZN-A-1041 Enteric Capsules

ZN-A-1041 50mg

ZN-A-1041 100mg BID DRUG

Orally 21days for one cycle

Also known as: ZN-A-1041 Enteric Capsules

ZN-A-1041 100mg

ZN-A-1041 200mg BID DRUG

Orally 21days for one cycle

Also known as: ZN-A-1041 Enteric Capsules

ZN-A-1041 200mg

ZN-A-1041 400mg BID DRUG

Orally 21days for one cycle

Also known as: ZN-A-1041 Enteric Capsules

ZN-A-1041 400mg

ZN-A-1041 600mg BID DRUG

Orally 21days for one cycle

Also known as: ZN-A-1041 Enteric Capsules

ZN-A-1041 600mg

ZN-A-1041 800mg BID DRUG

Orally 21days for one cycle

Also known as: ZN-A-1041 Enteric Capsules

ZN-A-1041 800mg

ZN-A-1041 1000mg BID DRUG

Orally 21days for one cycle

Also known as: ZN-A-1041 Enteric Capsules

ZN-A-1041 1000mg

ZN-A-1041 Level 1 +Capecitabine 1000 mg/m2 + Trastuzumab 8 mg/kg iv. First Cycle DRUG

ZN-A-1041 level 1 BID; Capecitabine 1000 mg/m2 BID Trastuzumab 8 mg/kg iv. First Cycle

Also known as: ZN-A-1041 Enteric Capsules

ZN-A-1041 level 1+Capecitabine 1000 mg/m2 + Trastuzumab 8 mg/kg iv. First Cycle

ZN-A-1041 Level 2 +Capecitabine 1000 mg/m2 + Trastuzumab 8 mg/kg iv. First Cycle DRUG

ZN-A-1041 level 2 BID; Capecitabine 1000 mg/m2 BID Trastuzumab 8 mg/kg iv. First Cycle

Also known as: ZN-A-1041 Enteric Capsules

ZN-A-1041 level 2+Capecitabine 1000 mg/m2+ Trastuzumab 8 mg/kg iv. First Cycle

ZN-A-1041 MAD +Capecitabine 1000 mg/m2 + Trastuzumab 8 mg/kg iv. First Cycle DRUG

ZN-A-1041 MAD BID; Capecitabine 1000 mg/m2 BID Trastuzumab 8 mg/kg iv. First Cycle

Also known as: ZN-A-1041 Enteric Capsules

ZN-A-1041 MAD+Capecitabine 1000 mg/m2+Trastuzumab 8 mg/kg iv. First Cycle

ZN-A-1041+Capecitabine + Trastuzumab 8 mg/kg iv. First Cycle DRUG

Base on 1b ZN-A-1041 dose Base on 1b Capecitabine dose Base on 1b Trastuzumab dose

Also known as: ZN-A-1041 Enteric Capsules

ZN-A-1041+Capecitabine+Trastuzumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. ECOG performance status of 0 to 1 2. HER2-positive is defined as Immunohistochemistry (IHC) (++) and Fluorescence In Situ Hybridization (FISH) positive, or IHC (+++).
• \. Phase 1a study will enroll patients with unresectable or metastatic HER2-positive advanced solid tumor; Phase 1b study will enroll patients with unresectable locally-advanced or metastatic HER2+ breast cancer.
• i. For patients who have no brain metastases, the following criteria should be met:
• Patients should be relapsed or refractory to existing therapy(ies) or have been intolerant of such therapies
• Have at least one extracranial measurable lesion by RECIST v1. 1 ii. For patients with brain metastasis, the following criteria should be met:
• \) Have received prior treatment or patient declined the above treatment; 2) Patients with HER2-positive gastric cancer must have previously received Trastuzumab 3) Do not require immediate local treatment during the trial period, and meet either of the following two criteria:
• For patients who have received previous local treatment (surgery, whole brain radiotherapy (WBRT) and stereotactic radiosurgery (SRS)) for brain metastases, stable or progression of intracranial lesions is required. Interval from prior local therapy could be 3 weeks from WBRT and 2 weeks from SRS.
• Symptomatic or not, patient has not received previous local treatment (surgery or radiotherapy) for brain metastases as long as no local therapy is needed during the trial period.
• iii. In Phase 1a, for patients who have received previous tyrosine kinase inhibitor (TKI) treatment, chemotherapy, antibody, or antibody-drug conjugate (ADC), the interval between the last treatment and the first administration of the study drug in this trial should be at least 2 weeks. In Phase 1b, for patients who have received previous trastuzumab or other antibodies, the interval between the last treatment and the first administration of the study drug in this trial should be at least 3 weeks.
• \. Phase 1c study will enroll patients with unresectable locally-advanced or metastatic HER2+ breast cancer with brain metastases.
• i. For patients with brain metastasis, patients do not require immediate local treatment during the trial period, and meet either of the following two criteria:
• For patients who have received previous local treatment (surgery, whole brain radiotherapy (WBRT) and stereotactic radiosurgery (SRS)) for brain metastases, stable or progression of intracranial lesions is required. Interval from prior local therapy could be 3 weeks from WBRT, 2 weeks from SRS and 4 weeks from surgery
• Symptomatic or not, patient has not received previous local treatment (surgery or radiotherapy) for brain metastases as long as no local therapy is needed during the trial period
• Have at least one measurable lesion and is suitable for accurate repeated assessable by RECIST 1.1, and the patient has an imaging-diagnosable intracranial lesion;
• Patients should not include suspected or confirmed meningeal metastases;

You may not qualify if:

• Subjects who have participated in any clinical study or received any clinical study drug within 4 weeks prior to the first administration
• There is evidence that other primary tumors are present at the same time;
• Previous cumulative dose of doxorubicin exceeds 360mg/m2 or its equivalent dose of similar drugs;
• Progressive neurologic impairment or increased intracranial pressure (including nausea, vomiting, blurred vision, headache, epilepsy, etc.)
• Any intracranial lesion thought to require immediate local therapy
• Require antiepileptic treatment (except for these patients with stable seizures require continuous Levetiracetam therapy).
• Ongoing use of systemic corticosteroids for control of symptoms of brain metastases at a total daily dose of \> 2 mg of dexamethasone (or equivalent)

Sponsors & Collaborators

• Suzhou Zanrong Pharma Limited: lead

Study Sites (1)

Cancer hospital Chinese academy of medical sciences

Beijing, Beijing Municipality, 100000, China

Location

MeSH Terms

Conditions

Brain Neoplasms

Interventions

BID protein, human; Trastuzumab

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Fei Ma, MD

  Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 10, 2020
• First Posted: July 27, 2020
• Study Start: October 15, 2020
• Primary Completion: April 16, 2024
• Study Completion: April 16, 2025
• Last Updated: August 11, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)