Overview
This is a Phase 1b, 2-part, multi-center, open-label study to evaluate the safety, tolerability, dosimetry, and pharmacokinetics (PK) of \[64Cu\]Cu-AKY-2519 and/or \[225Ac\]Ac-AKY-2519, as well as the preliminary anti-tumor activity of \[225Ac\]Ac-AKY-2519 in participants with B7-H3 imaging positive solid tumors.
Description
This Phase 1b study consists of two parts.
Part 1 is the dose escalation portion and will investigate ascending doses of \[225Ac\]Ac-AKY-2519 in patients with locally advanced or metastatic solid tumors, including non-small cell lung cancer (NSCLC), extensive stage-small cell lung cancer (ES-SCLC), metastatic castration-resistant prostate cancer (mCRPC), head and necks squamous cell carcinoma (HNSCC), esophageal squamous cell carcinoma (ESCC), and colorectal cancer (CRC). Part 1 will also incorporate a backfill strategy to evaluate two dose levels further.
Part 2 is the dose expansion portion and aims to assess the efficacy of \[225Ac\]Ac-AKY-2519 in two separate cohorts by indication:
- Cohort A: NSCLC
- Cohort B: Other solid tumors
Eligibility
Inclusion Criteria:
- Age ≥ 18 years
- Histologic or cytologic confirmation of locally advanced or metastatic NSCLC, ES-SCLC, HNSCC, ESCC, CRC or prostatic adenocarcinoma
- Radiologic confirmation on CT of at least one measurable tumor lesion per RECIST v1.1
- ECOG Performance Status of 0 or 1
- Adequate end-organ function
- Ability to give informed consent and comply with study requirements
- Patients with CNS metastases are eligible if they have received therapy and are neurologically stable, asymptomatic and not receiving corticosteroids
Exclusion Criteria:
- Prior treatment with a B7-H3 targeted therapy
- Prior treatment with a targeted radiotherapy
- Received an investigational agent within the previous 28 days
- Prior treatment with a cytotoxic chemotherapy, targeted therapy, biologic agent, immunotherapy or external-beam radiotherapy within the previous 28 days
- Impaired cardiac function or clinically significant cardiac disease
- Concurrent serious medical condition that would impair study participation or impact the assessment of treatment related toxicity
