Advanced Solid Tumor, Gastric Cancer, Head and Neck Squamous Cell Carcinoma, Metastatic Colorectal Carcinoma, Non-small Cell Lung Cancer, Pancreatic Ductal Adenocarcinoma, Renal Cell Carcinoma
Conditions
Keywords
FPI-2068, FPI-2107, FPI-2053, Actinium-225, 225Ac, Indium-111, 111In, Solid tumors, Targeted alpha therapy, TAT, Epidermal growth factor receptor, EGFR, Mesenchymal-epithelial transition factor, cMET, Bispecific antibody, Radioimmuno-SPECT agent, Radioimmuno-therapeutic agent, Monoclonal antibody, Bifunctional chelating agent, Radiopharmaceutical therapy, Alpha particle emitter, Directed bispecific monovalent antibody, bsAb, Bifunctional chelate, mCRC, HNSCC, NSCLC, PDAC, GC, RCC, RLT, Radioligand Therapy, EGFRm, EGFRwt
Brief summary
This is a first-in-human, Phase 1, non-randomized, multicenter, open-label clinical study designed to investigate the safety, tolerability, dosimetry, biodistribution, and pharmacokinetics (PK) of \[225Ac\]-FPI-2068, \[111In\]-FPI-2107, and FPI-2053 in metastatic and/or recurrent solid tumors (HNSCC, NSCLC, mCRC, PDAC, GC, RCC).
Detailed description
The study will be conducted in 2 parts: Part A: optimization of the FPI-2053 dose (treatment with dose level 1 of \[225Ac\]-FPI-2068 - fixed dose). Part B: dose escalation of \[225Ac\]-FPI-2068 with optimal FPI-2053. Part B will commence once the optimal dose of FPI-2053 is determined in Part A. The RP2D will be determined from Part B based on all available safety, efficacy, PK, and dosimetry information.
Interventions
DRUGFPI-2053
FPI-2053 is a bispecific antibody that targets EGFR and cMET
DRUG[111In]-FPI-2107
\[111In\]-FPI-2107 is an imaging agent in which indium-111 is conjugated to FPI-2053. Participants will have a fixed dose of \[111In\]-FPI-2107 followed by imaging scans (with or without pre-administration of FPI-2053).
DRUG[225Ac]-FPI-2068
\[225Ac\]-FPI-2068 is a radiopharmaceutical therapy in which an alpha emitter, actinium-225, is conjugated to FPI-2053. Participants will be dosed through IV administration every 56 days for up to 3 cycles of the Treatment Period.
Sponsors
AstraZeneca
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 130 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: Histologically and/or cytologically confirmed solid tumor that is metastatic, locally advanced, recurrent or inoperable. Disease that has progressed despite prior treatment, and for which additional effective standard therapy is not available or is contraindicated, not tolerable, or the participant refuses standard therapy. Measurable disease as defined by RECIST Version 1.1 ECOG Performance status of 0 or 1 Adequate organ function Key
Exclusion criteria
Previous treatment with any systemic radiopharmaceutical Prior anti-cancer therapy unless adequate washout and recovery from toxicities Contraindications to or inability to perform the imaging procedures required in this study Radiation therapy (RT) within 28 days prior to the first dose of \[111In\]-FPI-2107 Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (≥ once per month) Patients with known CNS metastatic disease unless treated and stable
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Evaluate safety and tolerability of [111In]-FPI-2107, FPI-2053, and [225Ac]-FPI-2068 | From informed consent up to approximately 5 years post last administration | Frequency, duration, and severity of AEs, DLTs, and changes in clinical, laboratory, and ECG parameters compared to baseline |
| Determine radiation dose of [111In]-FPI-2107 and [225Ac]-FPI-2068 to whole body, organs, and selected regions of interest. | Within 56 days of administration | Changes in uptake of \[111In\]-FPI-2107 and projected RAD of \[225Ac\]-FPI-2068 by imaging following the administration of varying doses of FPI-2053 |
| Determine the RP2D of [225Ac]-FPI-2068, given with or without FPI-2053 | 56 days post administration | Estimates of residence time and absorbed radiation doses to the whole body, organs, and selected regions of interest for \[111In\]-FPI-2107 and \[225Ac\]-FPI-2068. |
| Determine the effect of predose administration of varying doses of FPI-2053 on the radiation dosimetry of [111In]-FPI-2107 and [225Ac]-FPI-2068 to whole body, organs, and selected regions of interest. | 56 days post-administration | Changes in uptake of \[111In\]-FPI- 2107 and projected RAD of \[225Ac\]-FPI-2068 by imaging following the administration of varying doses of FPI-2053 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Assess preliminary anti-tumor activity of [225Ac]-FPI-2068 | Approximately 5 years post final administration | * Tumor assessments will be based on RECIST v1.1 (Eisenhauer et al, 2009) and will be performed every 8 weeks (± 1 weeks) after first \[225Ac\]-FPI-2068 dose. During Long term follow up will be every 3 months (± 2 weeks) for 2 years and then every 6 months for 3 years, or as clinically indicated or until disease progression. * Percentage changes in total ctDNA (VAF), compared to baseline |
| Tumor uptake of [111In]-FPI-2107 | Within 56 days of administration | • Tumor uptake of \[111In\]-FPI-2107 in selected regions of interest on SPECT/CT and/or planar images |
| Pharmacokinetics (PK) of [111In]-FPI-2107, and [225Ac]-FPI-2068, by measuring changes in clearance, AUC, Cmax, and half-life. | From first dose of investigation product until 56 days after the last dose of investigational product. | • Determine the plasma concentrations and PK parameters of \[111In\]-FPI-2107, and \[225Ac\]-FPI-2068 and the effect of pre-dose administration of FPI-2053 on the plasma concentrations and PK parameters of \[111In\]-FPI-2107. |
| To assess the immunogenicity of [111In]-FPI-2107, [225Ac]-FPI-2068, and FPI-2053 | From first dose of investigation product until 56 days after the last dose of investigational product. | • Presence of ADA for \[111In\]-FPI-2107, \[225Ac\]-FPI-2068, and FPI-2053 |
Countries
Canada, United States
Outcome results
None listed