An open-label, dose-escalation (Part 1), dose-expansion (Part 2) study to assess the safety, pharmacokinetics (PK), and preliminary efficacy of an active drug alone and in combination with paclitaxel or docetaxel.
In Part 1 (dose escalation), subjects will receive escalating doses of an active drug monotherapy (Part 1a) or an active drug in combination with paclitaxel or docetaxel (Part 1b).
In Part 2 (dose expansion), subjects will receive an active drug monotherapy or in combination therapy. The active drug monotherapy cohort will enroll subjects with relapsed or refractory (R/R) small cell lung cancer (SCLC) (Part 2a); the active drug plus a taxane (paclitaxel or docetaxel) combination cohort will enroll subjects with R/R non-small cell lung cancer (NSCLC) and breast cancer (Part 2b).
18 Years and older.
- Has a histologic or cytologic diagnosis of a malignant solid tumor.
- Subjects enrolled in Part 2a (monotherapy, dose expansion) must have small cell lung
cancer (SCLC) with tumors that express B7H3 above a given threshold per central
laboratory testing; subjects enrolled to Part 2b (combination therapy, dose expansion)
must have either NSCLC or HR-positive/HER2-negative breast cancer with tumors that
express B7H3 above a given threshold per central laboratory testing.
- Measurable disease defined by Response Evaluation Criteria in Solid Tumors (RECIST)
- An Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to
- Failure of at least 1 prior systemic chemotherapy including all available standard
therapies for subjects in the dose-escalation phase (Parts 1a and 1b).
- All subjects with breast cancer for subjects in the dose-expansion phase (Part 2b
only) must have the following:
- locally advanced or metastatic HR-positive/HER2-negative breast cancer after
failing cyclindependent kinase (CDK)4/6 inhibitor-based therapy.
- HR-positivity and HER-2-negativity should be confirmed based on American Society
of Clinical Oncology (ASCO)/College of American Pathologists (CAP) criteria.
- All subjects with non-small cell lung cancer (NSCLC) for subjects in the
dose-expansion phase (Part 2b only) must have R/R NSCLC after at least 1 line of
- All subjects with SCLC in the dose-expansion phase (Part 2a only) must have R/R SCLC
from 2 lines of therapy which the first line is platinum-based. In addition, 1 of the
2 lines must have included an anti-PD-1/PD-L1.
- All subjects with either breast cancer or NSCLC must have the following: exposure to
prior taxane-based therapy; no history of taxane allergy (Part 1b and Part 2b only);
and disease that has relapsed or progressed at least 2 months after most recent
exposure to any taxane-based therapy.
- Available tumor tissue suitable for immunohistochemistry testing.
- Adequate kidney, liver, and hematologic laboratory values as described in the
- Untreated brain or meningeal metastases (subjects with a history of metastases may be
eligible based on details described in the protocol).
- Grade 2 or higher peripheral neuropathy (only applies to subjects who would receive
- Unresolved Grade 2 or higher toxicities related to previous anticancer therapy except
- Known active infection of hepatitis B, hepatitis C, or human immunodeficiency virus
with exceptions as described in the protocol.
- Recent history (within 6 months) of congestive heart failure (defined in the
protocol), ischemic cardiovascular event, cardiac arrhythmia requiring pharmacological
or surgical intervention, pericardial effusion, or pericarditis.
- For combination therapy only (Parts 1b and 2b), history of serious allergic reaction
to any taxane or any ingredients used in taxane formulation.