Breast Cancer, Colorectal Cancer, GRPR-positive Solid Tumors, Prostate Cancer
Conditions
Keywords
breast cancer, prostate cancer, colorectal cancer (CRC), GRPR-positive solid tumors, radiopharmaceuticals, theranostics
Brief summary
This is a Phase 1-1b multicenter clinical study to evaluate the safety, efficacy, and dosimetry of \[177Lu\]Lu-A9-0631 and \[225Ac\]Ac-0642 in participants with Gastrin-Releasing Peptide Receptor (GRPR) expressing locally advanced, unresectable or metastatic solid tumors.
Detailed description
This is a multicenter, open-label Phase 1-1b study of \[177Lu\]Lu-A9-0631 and \[225Ac\]Ac-A9-0642 in subjects with Gastrin-Releasing Peptide Receptor (GRPR) expressing locally advanced, unresectable or metastatic solid tumors. The study consists of two parts (Phase 1 and 1b). Phase 1 is the dose escalation portion of the study. The aim of the Phase 1 is to evaluate the safety and tolerability as well as the normal organ and tumor dosimetry of \[177Lu\]Lu-A9-0631 and \[225Ac\]Ac-A9-0642, and to determine the maximum tolerated dose (MTD) and the recommended Phase 2 dose (RP2D). Phase 1b will be the dose expansion portion of the study. The aim of the Phase 1b will be to further evaluate the safety, efficacy, and normal organ and tumor dosimetry of \[177 Lu\]Lu-A9-0631 and \[225Ac\]Ac-A9-0642 administered at the RP2D in subjects with (1) Locally advanced, unresectable, or metastatic HR+/HER2- breast cancer; (2) Locally advanced, unresectable, or metastatic prostate cancer; (3) Locally advanced, unresectable, or metastatic CRC; and (4) Other locally advanced, unresectable, or metastatic GRPR-positive solid tumors.
Interventions
DIAGNOSTIC_TEST[68Ga]Ga-A9-6217
Administered IV
DIAGNOSTIC_TESTLow dose [177Lu]Lu-A9-0631
Administered IV
DRUG[177Lu]Lu-A9-0631
Administered IV
DRUG[225Ac]Ac-A9-0642
Administered IV
Sponsors
Alpha-9 Oncology USA Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participant has provided written informed consent prior to any study-specific procedure. * Age ≥ 18 years old. * Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. * Have measurable target lesion per RECIST v1.1. * Progression from, intolerant to, or ineligible for (due to unavailability or contraindication) local standard of care therapies and have one of the following locally advanced or metastatic tumor types: prostate cancer; HR+/HER2- breast cancer; colorectal cancer; and GRPR-positive solid tumors. * Have GRPR-expressing disease as confirmed by PET / CT or SPECT imaging. * Adequate organ function within 14 days of first administration of investigational therapeutic product. * At least 4 weeks from prior major surgery.
Exclusion criteria
* Received anticancer treatment including but not limited to chemotherapy, antibody therapy, immunotherapy, gene therapy, vaccine therapy, angiogenesis inhibitors, or experimental drugs ≤ 14 days prior (≤ 28 days prior in case of checkpoint inhibitor therapy and other antibody therapies) or 5 half-lives, (t1/2) whichever is shorter, to the administration of therapeutic investigational product. * History of uncontrolled allergic reactions and/or known or expected hypersensitivity to a peptide-based imaging or therapeutic agent or any excipient present in either of the therapeutic investigational products. * Major surgery within 4 weeks of planned first dose of the therapeutic investigational product. * Prior external beam radiation therapy to more than 25% of the bone marrow. * Pregnant, breastfeeding, or unwilling to practice birth control during participation in the study. * Any active infection.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1-1b: Incidence of Adverse Events by Frequency, Duration, and Severity | From the first dose of study drug up to the End of Treatment (30 days after the last dose) | An AE is defined as any untoward medical occurrence in a participant administered study drug, which does not necessarily have to have a causal relationship with the study drug. The number of patients experiencing an AE in Part 1 will be reported. |
| Phase 1: Number of Patients with Dose-Limiting Toxicities (DLTs). | Up to 28 days following first study treatment | DLTs is defined as any predefined AE occurring during the DLT observation period. |
| Phase 1: Maximum tolerated dose (MTD) | Up to 28 days following first study treatment | Incidence of dose-limiting toxicity (DLT) per dose level of \[177Lu\]Lu-A9-0631 and/or \[225Ac\]Ac-A9-0642. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1-1b: Absorbed dose estimates (Gy) in normal organs for [177Lu]Lu-A9-0631 and/or [225Ac]Ac-A9-0642 | Up to 7 days after each injection for up to 6 cycles (each cycle is 28 days) | — |
| Phase 1-1b: Objective Response Rate (ORR) | Every 8 ± 1 weeks until radiographic disease progression or up to 12 months after the last dose of [177Lu]Lu-A9-0631 and/or [225Ac]Ac-A9-0642 | Objective response rate is defined as the percentage of patients who achieved a best overall response of confirmed Complete Response (CR) or Partial Response (PR), as determined by the investigator based on RECIST 1.1, by dose level. |
Countries
Australia
Contacts
CONTACTStephen Hull, MD
STUDY_DIRECTORStephen Hull, MD
Alpha 9 Oncology
Outcome results
None listed