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

Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18-130
SponsorAstraZeneca

About this trial

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).

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

None

Disqualifiers

None

Trial design

Design model

Sequential

Treatments tested in this trial

  • FPI-2053

    Drug

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

  • [111In]-FPI-2107

    Drug

    \[111In\]-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-2068

    Drug

    \[225Ac\]-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.

Treatment groups

70 Participants
are divided into 1 treatment group
Group A: Dose Exploration and Dose EscalationExperimental treatment 3 interventions

Trial outcomes

Primary outcomes

1

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
2

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
3

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
4

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

1

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
2

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
3

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.
4

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.

Other outcomes

Sponsors and contacts

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