Eligibility Details:
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
common.study.methods.has-drugs-yes
common.study.methods.is-healthy-yes
