A Phase 1, Dose-escalation Study of [225Ac]-FPI-2068 in Adult Patients With Advanced Solid Tumours

Phase 1RecruitingNCT06147037

AstraZeneca70 enrolled

Overview

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).

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Advanced Solid Tumor Metastatic Colorectal Carcinoma Head and Neck Squamous Cell Carcinoma

Interventions

FPI-2053DRUG

FPI-2053 is a bispecific antibody that targets EGFR and cMET

[111In]-FPI-2107DRUG

\[111In\]-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).

[225Ac]-FPI-2068DRUG

\[225Ac\]-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.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 130 Years

Medical Language ↔ Plain English

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

Locations (15)

Research Site

Irvine, California, United States

WITHDRAWN

Research Site

Palo Alto, California, United States

RECRUITING

Research Site

Santa Monica, California, United States

NOT_YET_RECRUITING

Research Site

Chicago, Illinois, United States

RECRUITING

Research Site

Boston, Massachusetts, United States

RECRUITING

Research Site

St Louis, Missouri, United States

WITHDRAWN

Research Site

Omaha, Nebraska, United States

RECRUITING

Research Site

Cleveland, Ohio, United States

RECRUITING

Research Site

Pittsburgh, Pennsylvania, United States

WITHDRAWN

Research Site

Houston, Texas, United States

RECRUITING

...and 5 more locations

Outcomes

Primary Outcomes

Evaluate safety and tolerability of [111In]-FPI-2107, FPI-2053, and [225Ac]-FPI-2068

Frequency, duration, and severity of AEs, DLTs, and changes in clinical, laboratory, and ECG parameters compared to baseline

Time frame: From informed consent up to approximately 5 years post last administration

Determine radiation dose of [111In]-FPI-2107 and [225Ac]-FPI-2068 to whole body, organs, and selected regions of interest.

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

Time frame: Within 56 days of administration

Determine the RP2D of [225Ac]-FPI-2068, given with or without FPI-2053

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.

Time frame: 56 days post administration

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.

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

Time frame: 56 days post-administration

Secondary Outcomes

Assess preliminary anti-tumor activity of [225Ac]-FPI-2068

* 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

Time frame: Approximately 5 years post final administration

Tumor uptake of [111In]-FPI-2107

• Tumor uptake of \[111In\]-FPI-2107 in selected regions of interest on SPECT/CT and/or planar images

Time frame: Within 56 days of administration

Pharmacokinetics (PK) of [111In]-FPI-2107, and [225Ac]-FPI-2068, by measuring changes in clearance, AUC, Cmax, and half-life.

• 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.

Time frame: From first dose of investigation product until 56 days after the last dose of investigational product.

To assess the immunogenicity of [111In]-FPI-2107, [225Ac]-FPI-2068, and FPI-2053

• Presence of ADA for \[111In\]-FPI-2107, \[225Ac\]-FPI-2068, and FPI-2053

Time frame: From first dose of investigation product until 56 days after the last dose of investigational product.

A Phase 1, Dose-escalation Study of [225Ac]-FPI-2068 in Adult Patients With Advanced Solid Tumours

Overview

Conditions

Interventions

Eligibility

Locations (15)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts