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NCT05593094 | RECRUITING | Advanced Solid Tumors

A Phase 1 Trial of ZN-A-1041 Enteric Capsules or Combination in Patients With HER2-Positive Advanced Solid Tumors
Sponsor:

Suzhou Zanrong Pharma Limited

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 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).

Condition or disease

Advanced Solid Tumors

HER2-positive Breast Cancer

Intervention/treatment

ZN-A-1041 50mg BID

ZN-A-1041 100mg BID

ZN-A-1041 200mg BID

ZN-A-1041 400mg BID

ZN-A-1041 600mg BID

ZN-A-1041 800mg BID

ZN-A-1041 1000mg BID

ZN-A-1041 + T-DM1 3.6 mg/kg iv. for Phase1b

ZN-A-1041 + T-Dxd 5.4 mg/kg iv. for Phase1b

ZN-A-1041 + PHESGO / Herceptin plus Perjeta injection for Phase1b

ZN-A-1041 + T-DM1 3.6 mg/kg iv. for Phase1c

ZN-A-1041 + T-Dxd 5.4 mg/kg iv. for Phase1c

ZN-A-1041 + PHESGO / Herceptin plus Perjeta injection for Phase1c

Phase

PHASE1

Detailed Description:

Phase 1a of the study will adopt the "modified 3+3" dose escalation design with a total of 7 planned dose levels. Patients with HER2-positive advanced solid tumor (including those with brain metastases) will be enrolled to receive a single-dose administration of ZN-A-1041 followed by multiple-dose administration of ZN-A-1041.Phase 1b of the study will adopt the "traditional 3+3" dose escalation design. The dose levels will be based on the results of the Phase 1a study and the results of a food effect study. In Phase 1b, patients with unresectable locally-advanced or metastatic HER2+ breast cancer with and without brain metastasis will be enrolled in three arms: Arm1 will receive multiple doses of ZN-A-1041 in combination with T-DM1; Arm2 will receive multiple doses of ZN-A-1041 in combination with T-DXd. Arm 3 will receive multiple doses of ZN-A-1041 in combination with PHESGO or Herceptin plus Perjeta after Herceptin plus Perjeta and 4-8-cycle treatment of taxane. Patients will be assessed for an appropriate arm by the sponsor and the investigator at the time of consent. Patients with unresectable locally-advanced or metastatic HER2+ breast cancer with and without brain metastasis are planned to be enrolled in Phase 1c of the study: Arm1 will receive multiple doses of ZN-A-1041 in combination with T-DM1; Arm2 will receive multiple doses of ZN-A-1041 in combination with T-DXd; Arm 3 will receive multiple doses of ZN-A-1041 in combination with PHESGO or Herceptin plus Perjeta after Herceptin plus Perjeta or T-DXd based induction regimen. Patients will be assessed for an appropriate arm by the sponsor and the investigator at the time of consent. Arm1 of Phase 1c can start independently after the DLT observation period of the last patient in Phase 1b Arm1. Arm 2 of Phase 1c can start independently after the DLT observation of the last patient in Phase 1b Arm 2. Arm 3 of Phase 1c can start independently after the DLT observation of the last patient in Phase 1b Arm 3. The dose levels used in Phase 1c will be based on the recommended doses obtained from the Phase 1b study. Each phase of the study includes a screening period (from 28 days prior to the first administration of the study drug), a treatment period (until there are no clinical benefits as deemed by the Investigator, disease progression, death, intolerable toxicity, withdrawal of informed consent, loss of follow-up, or the start of new anti-tumor treatment), and a follow-up period (until 28 days after the last administration of the study drug). During the trial, the safety, tolerability, PK and efficacy data of ZN-A-1041 as monotherapy and in combination in the subjects will be collected and analyzed, thereby providing RP2D for subsequent future clinical trials.

Study Type : INTERVENTIONAL
Estimated Enrollment : 210 participants
Masking : NONE
Primary Purpose : TREATMENT
Official Title : A Phase 1 Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of ZN-A-1041 Enteric Capsules as a Single Agent or in Combination in Patients With HER2-Positive Advanced Solid Tumors
Actual Study Start Date : 2020-10-15
Estimated Primary Completion Date : 2025-10-30
Estimated Study Completion Date : 2026-10-30

Information not available for Arms and Intervention/treatment

Ages Eligible for Study: 18 Years
Sexes Eligible for Study: ALL
Accepts Healthy Volunteers:
Criteria
* Inclusion Criteria
  • 1. ECOG performance status of 0 to 1
  • 2. HER2 positive is defined as Immunohistochemistry (IHC) (++) and Fluorescence In Situ Hybridization (FISH) positive, or IHC (+++).
  • 3. Phase 1a study will enroll patients with unresectable or metastatic HER2-positive advanced solid tumor.
  • For patients who have no brain metastases, the following criteria should be met:
  • 1. Patients should be relapsed or refractory to existing therapy(ies) or have been intolerant of such therapies
  • 2. Patients with HER2-positive breast cancer should have previously received Trastuzumab, Pertuzumab, Trastuzumab emtansine(T-DM1) and a taxane.
  • 3. Patients with HER2-positive gastric cancer must have previously received trastuzumab.
  • 4. Have measurable or non-measurable disease assessable by RECIST 1.1.
  • For patients with brain metastasis, the following criteria should be met:
  • 1. Patients with HER2-positive breast cancer must have received prior treatment with Trastuzumab, Pertuzumab and T-DM1, and a taxane 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: i) 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; ii) 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.
  • 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.
  • 4. Phase 1b and Phase 1c study will enroll patients with unresectable locally advanced or metastatic HER2+ breast cancer.
  • For Phase 1b patients who have no brain metastases, the following criteria should be met:
  • 1. For arm 1 and arm 2, patients should be relapsed or refractory to existing therapy(ies), with a history of prior treatment with trastuzumab and a taxane. For arm3, patients have received 4-8 cycles (21-day cycles) of previous treatment with trastuzumab, pertuzumab, and taxane as first-line therapy for advanced HER2+ breast cancer with no evidence of disease progression.
  • 2. Have measurable or non-measurable disease assessable by RECIST 1.1
  • For Phase 1c patients who have no brain metastases, the following criteria should be met:
  • 1. For arm 1 and arm 2, patients should be refractory to existing therapy(ies), with a history of prior treatment with trastuzumab. For arm3, patients have received a pertuzumab plus trastuzumab or T-DXd for advanced HER2+breast cancer with no evidence of disease progression.
  • 2. In arms 1 and 2, patients should have at least one measurable lesion either extracranially or intracranially per RECIST v1.1.
  • For patients with brain metastasis, the following criteria should be met:
  • 1. For arm 1 and arm 2 of phase 1b, patients should be relapsed or refractory to existing therapy(ies), with a history of prior treatment with trastuzumab and a taxane. For arm3, patients have received 4-8 cycles (21-day cycles) of previous treatment with trastuzumab, pertuzumab, and taxane as first-line therapy for advanced HER2+ breast cancer with no evidence of disease progression. For arm 1 and arm 2 of phase 1c, patients should be refractory to existing therapy(ies), with a history of prior treatment with trastuzumab. For arm3, patients have received previous treatment with a pertuzumab plus trastuzumab or T-DXd for advanced HER2+ breast cancer with no evidence of disease progression (except brain metastases).
  • 2. Do not require immediate local treatment during the trial period, and meet either of the following two criteria: i) 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; ii) 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.
  • 5. Suspected or confirmed leptomeningeal metastasis are allowed.
  • 6. In Phase 1b arm1 and arm2, 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. For arm3, patients should not have prior treatment for unresectable locally-advanced or metastatic HER2+ breast cancer with and without brain metastasis, except for ongoing Herceptin, Perjeta or PHESGO and taxane.
  • 7. In Phase 1c arm1 and arm2, Patients should not have received prior treatment with tucatinib, afatinib, or any other investigational anti-HER2, anti-EGFR, or HER2 TKI agent. Prior treatment with lapatinib or neratinib within 12 months of starting study treatment (except in cases where they were given for ≤ 21 days and was discontinued for reasons other than disease progression or severe toxicity). Prior treatment with pyrotinib for recurrent of mBC (except in cases where pyrotinib was given for ≤ 21 days and was discontinued for reasons other than disease progression or severe toxicity). For arm3, patients should not have prior treatment for unresectable locally-advanced or metastatic HER2+ breast cancer with and without brain metastasis, except for ongoing Herceptin, Perjeta or PHESGO or T-Dxd based induction.
  • * Exclusion Criteria
    • 1. Subjects who have participated in any clinical study or received any clinical study drug within 4 weeks prior to the first administration except for on-going Herceptin, Perjeta or PHESGO in arm3
    • 2. CNS Exclusion - Based on screening brain MRI and clinical assessment
    • 1. Progressive neurologic impairment or increased intracranial pressure (including nausea, vomiting, blurred vision, headache, epilepsy, etc.)
    • 2. Any intracranial lesion thought to require immediate local therapy
    • 3. Require antiepileptic treatment (except for these patients with stable seizures require continuous Levetiracetam therapy).
    • 4. Ongoing use of systemic corticosteroids for control of symptoms of brain metastases at a total daily dose of \> 2 mg of dexamethasone (or equivalent)
A Phase 1 Trial of ZN-A-1041 Enteric Capsules or Combination in Patients With HER2-Positive Advanced Solid Tumors

Location Details

NCT05593094

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Locations

RECRUITING

United States, Arizona

ACRC/Arizona Clinical Research Center, Inc

Tucson, Arizona, United States, 85715

RECRUITING

United States, California

TOI Clinical Research

Cerritos, California, United States, 90703-2684

RECRUITING

United States, California

Innovative Clinical Research Institute

Whittier, California, United States, 90603

RECRUITING

United States, Massachusetts

Dana-Farber Cancer Institute

Boston, Massachusetts, United States, 02215

RECRUITING

United States, Road cancer

Barbara Ann Karmanos Cancer center

Detroit, Road cancer, United States, 48201

RECRUITING

United States, North Carolina

Duke Cancer Institute

Durham, North Carolina, United States, 27710

RECRUITING

United States, Texas

Md Anderson Cancer center

Houston, Texas, United States, 77030

ACTIVE NOT RECRUITING

Australia, Victoria

Andrew Love Cancer Center

Geelong, Victoria, Australia, 3220

ACTIVE NOT RECRUITING

Australia, Victoria

Sunshine Hospital - Australia

St Albans, Victoria, Australia, 3021

ACTIVE NOT RECRUITING

France, Nord

Center Oscar Lambret - PPDS

Lille, Nord, France, 59000

ACTIVE NOT RECRUITING

France,

Center Léon Bérard Regional Center for the fight against Rhône Alpes cancer

Lyon, France, 69373

ACTIVE NOT RECRUITING

France,

Institut Claudius Regaud - PPDS

Toulouse, France, 31059

ACTIVE NOT RECRUITING

New Zealand,

Auckland City Hospital

Auckland, New Zealand, 1023

ACTIVE NOT RECRUITING

Spain,

Dr. Rosell-Hospital Universitari Dexeus-Group Quironsalud Institute

Barcelona, Spain, 8028

ACTIVE NOT RECRUITING

Spain,

Vall Dhebron Oncologica Research Institute (VHIO) - Epon

Barcelona, Spain, 8035

ACTIVE NOT RECRUITING

Spain,

Clinic Hospital in Barcelona

Barcelona, Spain, 8036

ACTIVE NOT RECRUITING

Spain,

Jaen University Hospital

Jaén, Spain, 23007

RECRUITING

Spain,

Ramon and Cajal University Hospital

Madrid, Spain, 28034

ACTIVE NOT RECRUITING

Spain,

San Carlos Clinic Hospital

Madrid, Spain, 28040

ACTIVE NOT RECRUITING

Spain,

Santiago University Clinic Hospital

Santiago de Compostela, Spain, 15706

ACTIVE NOT RECRUITING

Spain,

Virgen Macarena University Hospital

Sevilla, Spain, 41009

RECRUITING

Spain,

Valencian Institute of Oncologia Foundation

Valencia, Spain, 46026

ACTIVE NOT RECRUITING

United Kingdom, Lancashire

The Christie - PPDS

Manchester, Lancashire, United Kingdom, M20 4BX