Clinical Trials /

Trial of ZW25 in Patients With Advanced HER2-expressing Cancers

NCT02892123

Description:

This is a first-in-human, 3-part study to investigate the safety, tolerability, and effectiveness of ZW25 by itself and combined with selected chemotherapy agents in patients with locally advanced (unresectable) and/or metastatic human epidermal growth factor receptor 2 (HER2)-expressing cancers. This study will also the evaluate the way the body absorbs, distributes, and eliminates ZW25 (pharmacokinetics or PK).

Related Conditions:
  • Adenocarcinoma of the Gastroesophageal Junction
  • Breast Carcinoma
  • Colorectal Carcinoma
  • Gastric Carcinoma
  • Malignant Solid Tumor
  • Non-Small Cell Lung Carcinoma
  • Ovarian Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Trial of ZW25 in Patients With Advanced HER2-expressing Cancers
  • Official Title: Phase I Trial of ZW25 in Patients With Locally Advanced (Unresectable) and/or Metastatic HER2-expressing Cancers

Clinical Trial IDs

  • ORG STUDY ID: ZWI-ZW25-101
  • NCT ID: NCT02892123

Conditions

  • HER2-expressing Cancers

Interventions

DrugSynonymsArms
ZW25ZW25 Monotherapy and ZW25 Combination Therapy

Purpose

This is a first-in-human, 3-part study to investigate the safety, tolerability, and effectiveness of ZW25 by itself and combined with selected chemotherapy agents in patients with locally advanced (unresectable) and/or metastatic human epidermal growth factor receptor 2 (HER2)-expressing cancers. This study will also the evaluate the way the body absorbs, distributes, and eliminates ZW25 (pharmacokinetics or PK).

Detailed Description

      Part 1 of the study will evaluate increasing doses of ZW25 to find the highest dose of ZW25
      that does not cause unacceptable side effects (maximum-tolerated dose or MTD), the lowest
      safe dose with the highest rate of effectiveness (optimal biological dose or OBD), and/or
      other recommended dosages (RDs) of ZW25 in up to 7 dose-specific cohorts. Eligible patients
      include those with selected HER2-expressing locally advanced (unresectable) and/or metastatic
      cancers that have progressed after receipt of all therapies known to confer clinical benefit
      (or ineligible to receive therapy).

      Part 2 of the study will further evaluate the safety, tolerability, and efficacy of ZW25 in
      patients with selected HER2-expressing locally advanced (unresectable) and/or metastatic
      cancers that have progressed after receipt of all therapies known to confer clinical benefit
      (or ineligible to receive therapy) in up to 5 separate disease-specific cohorts.

      Part 3 of the study will evaluate the safety, tolerability, and efficacy of ZW25 combined
      with selected chemotherapy agents, including paclitaxel, capecitabine, or vinorelbine.
      Patients with selected HER2-expressing locally advanced (unresectable) and/or metastatic
      cancers that have progressed after at least 1 and no more than 3 prior systemic chemotherapy
      regimens will be evaluated in this part of the study.
    

Trial Arms

NameTypeDescriptionInterventions
ZW25 Monotherapy and ZW25 Combination TherapyExperimental
  • ZW25

Eligibility Criteria

        Inclusion Criteria:

          1. HER2-expressing cancer as follows:

             Part 1:

               -  Cohorts 1 - 3: Any locally advanced (unresectable) and/or metastatic
                  HER2-expressing (HER2 1+, 2+, or 3+ by IHC) cancer (including but not limited to
                  breast, gastric, ovarian, colorectal and non-small cell lung) that has progressed
                  after receipt of all therapies known to confer clinical benefit

               -  Cohorts 4 - 6:

                    -  HER2 IHC 2+ /FISH- breast cancer or gastroesophagel adenocarcinoma (GEA)

                    -  HER2 IHC 3+ or HER2 IHC 2+ /FISH+ breast cancer or GEA

                    -  Any other HER2 IHC 3+ or FISH+ cancer

                         -  HER2-overexpressing (3+ by IHC) or HER2-2+ and FISH+ breast cancer must
                            have progressed after prior treatment with trastuzumab, pertuzumab, and
                            T-DM1

                         -  HER2-overexpressing (3+ by IHC) or HER2-2+ and FISH+ GEA must have
                            progressed after prior treatment with trastuzumab

                              -  Patients with colorectal cancer must be KRAS wild-type

                              -  Patients with NSCLC must have ALK wild-type, EGFR wild-type, and
                                 ROS1 fusion negative as determined by standard methods

               -  Cohort 7 (only at selected sites): HER2 IHC 3+, HER2 IHC 2+ /FISH+, or HER2 IHC
                  2+ /FISH- breast cancer

             Part 2:

             Locally advanced (unresectable) and/or metastatic cancer that has progressed after
             receipt of all therapies known to confer clinical benefit (unless ineligible to
             receive a specific therapy) as follows:

               -  Cohort 1: HER2 IHC 2+/FISH- breast cancer

               -  Cohort 2: HER2 IHC 3+ or HER2 IHC 2+/FISH+ breast cancer

               -  Cohort 3: HER2 IHC 2+/FISH- GEA

               -  Cohort 4: HER2 IHC 3+ or HER2 IHC 2+/FISH+ GEA

               -  Cohort 5: Any other HER2 IHC 3+ or IHC 2+/FISH+ cancer, including the following:

                    -  Cohort 5a: HER2 IHC 3+ or IHC 2+/FISH+ GI cancers other than GEA (patients
                       with colorectal cancer must be KRAS wild-type.)

                    -  Cohort 5b: Any other HER2 IHC 3+ or IHC 2+/FISH+ solid tumor types that are
                       not breast or GI cancers (patients with NSCLC must have ALK wild-type, EGFR
                       wild-type, and ROS1 fusion negative as determined by standard methods;
                       patients with ovarian cancers must be KRAS wild type.)

             Part 3:

             Locally advanced (unresectable) and/or metastatic cancer as follows:

               -  HER2 IHC 1+ or IHC2+/FISH- breast cancer patients who have received at least 1
                  and no more than 3 prior systemic chemotherapy regimens

               -  HER2 IHC 3+ or IHC 2+/FISH+ breast cancer patients who have received prior
                  therapy with trastuzumab, pertuzumab, and T-DM1, at least 1 and no more than 3
                  prior systemic chemotherapy regimens

               -  HER2 IHC 2+ or 3+ FISH+ or FISH- GEA patients who have received at least 1 and no
                  more than 3 prior systemic chemotherapy regimens

          2. ≥ 18 years of age

          3. ECOG performance status of 0 or 1

          4. Life expectancy of at least 3 months per the investigator's assessment.

          5. Adequate organ function

          6. Adequate cardiac left ventricular function, as defined by a LVEF >/= institutional
             standard of normal

          7. For Part 1 Cohorts 1 - 3: evaluable disease (target or non-target lesions) per RECIST
             version 1.1. For Part 1 Cohorts 4 - 6, and Parts 2 and 3: measurable disease (target
             lesions) per RECIST version 1.1

          8. Able to provide tumor sample (fresh or archived)

        Exclusion Criteria:

          1. Experimental therapies within 4 weeks before first ZW25 dosing

          2. Treatment with other cancer therapy not otherwise specified within 4 weeks before ZW25
             dosing

          3. Anthracyclines within 90 days before first ZW25 dosing or lifetime load exceeding 300
             mg/m² adriamycin or equivalent

          4. Trastuzumab, pertuzumab, lapatinib, or T‑DM1 within 3 weeks before first ZW25 dosing

          5. Untreated brain metastases (patients with treated brain mets who are off steroids and
             are stable for at least 1 month at the time of screening are eligible)

          6. Pregnant or breast-feeding women

          7. History of life-threatening hypersensitivity to monoclonal antibodies or to
             recombinant proteins or excipients in drug formulation

          8. Acute or chronic uncontrolled renal disease, pancreatitis or liver disease (with
             exception of patients with Gilbert's Syndrome, asymptomatic gall stones, liver
             metastases, or stable chronic liver disease per investigator assessment)

          9. Peripheral neuropathy >Grade 2

         10. Clinically significant interstitial lung disease

         11. Known active hepatitis B or C or known infection with HIV

         12. Immunosuppressive corticosteroids equivalent to >15mg/day of prednisone within 2 weeks
             before first ZW25 dose

         13. QTc Fridericia (QTcF) >450 ms

         14. Having clinically significant cardiac disease such as ventricular arrhythmia requiring
             therapy, uncontrolled hypertension or any history of symptomatic CHF

         15. Having known myocardial infarction or unstable angina within 6 months before first
             ZW25 dosing
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:The proportion of patients who experience dose-limiting toxicities (DLTs) (Part 1)
Time Frame:Up to 8 months
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Serum concentrations of ZW25
Time Frame:Throughout the duration of the study; up to 2 years
Safety Issue:
Description:
Measure:The proportion of patients who develop detectable anti-drug antibodies
Time Frame:Throughout the duration of the study; up to 2 years
Safety Issue:
Description:
Measure:The proportion of patients with an objective response (partial response or complete response) as defined by RECIST 1.1 criteria
Time Frame:Throughout the duration of the study; up to 2 years
Safety Issue:
Description:
Measure:Progression free survival as defined by RECIST 1.1 criteria
Time Frame:Throughout the duration of the study; up to 2 years
Safety Issue:
Description:
Measure:The proportion patients who experience laboratory abnormalities and/or adverse events as defined by CTCAE v4.03 that are related to treatment (Part 1)
Time Frame:Throughout the duration of the study; up to 2 years
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Zymeworks Inc.

Trial Keywords

  • HER2
  • Bispecific antibody
  • Biparatopic antibody
  • Immunotherapy
  • Breast cancer
  • Gastroesophageal adenocarcinoma (GEA)
  • Gastric cancer
  • Gastroesophageal junction (GEJ) cancer
  • Ovarian cancer
  • Non-small cell lung cancer (NSCLC)
  • Chemotherapy
  • Paclitaxel
  • Capecitabine
  • Vinorelbine

Last Updated

December 16, 2019