A Study of [177Lu]Lu-A9-0631 and [225Ac]Ac-A9-0642 With [68Ga]Ga-A9-6217 or [177Lu]Lu-A9-0631 Imaging in GRPR+ Solid Tumors

A Phase 1-1b Study to Evaluate the Safety, Efficacy, and Dosimetry of [177Lu]Lu-A9-0631, [225Ac]Ac-A9-0642, and [68Ga]Ga-A9-6217 in Participants With GRPR+ Tumors

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.

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.

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.