FPT155 in Patients With Advanced Solid Tumors (FPT155-001)

A Phase 1a/1b Study of FPT155 in Patients With Advanced Solid Tumors

This study is a Phase 1 open-label, first-in-human, multicenter study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and activity of FPT155 as monotherapy in patients with advanced solid tumors.

Study Overview

• Status: Terminated
• Conditions: Advanced Solid Tumors
• Intervention / Treatment: Biological: FPT155; Biological: pembrolizumab

Detailed Description

This Phase 1 study is comprised of dose escalation and cohort expansions for FPT155 monotherapy and for FPT155 in combination with pembrolizumab. Monotherapy dose escalation is designed with initial accelerated titration followed by a standard 3+3 dose escalation; combination dose escalation uses a standard 3+3 design. Patients will remain on study treatment until progression of disease, unacceptable toxicity, or other specified reason for discontinuation.

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Chris O'Brien Lifehouse
    • Darlinghurst, New South Wales, Australia, 2010
      • St Vincent's Hospital Sydney
    • Randwick, New South Wales, Australia, 2031
      • Scientia Clinical Research
  • Queensland
    • Auchenflower, Queensland, Australia, 4066
      • ICON
  • Victoria
    • Heidelberg, Victoria, Australia, 3084
      • Olivia Newton-John Cancer Center
    • Malvern, Victoria, Australia, 3144
      • Cabrini Hospital
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Linear Clinical Research
• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 03722
    • Severance Hospital, Yonsei University Health System
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center
  • Gyeonggi-do
    • Goyang-Si, Gyeonggi-do, Korea, Republic of, 10408
      • National Cancer Center
    • Suwon-Si, Gyeonggi-do, Korea, Republic of, 16247
      • St Vincent Hospital of the Catholic University of Korea

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologically confirmed solid tumors (except primary central nervous system tumors). For patients enrolled for treatment with FPT155+pembrolizumab: histologically confirmed non-small cell lung cancer not eligible for curative therapy.
• Disease that is unresectable, locally advanced, or metastatic and has progressed following all standard treatments or is not appropriate for standard treatments
• All patients must have at least one measurable lesion at baseline according to RECIST v1.1
• Availability of archival tumor tissue and consent to provide archival tumor for retrospective biomarker analysis, or consent to undergo a fresh tumor biopsy during screening
• For patients participating in cohort expansions: consent to undergo a mandatory fresh tumor biopsy during screening and on treatment
• ECOG performance status of 0 or 1
• Prior radiotherapy must be completed at least 2 weeks before first dose of study treatment administration. No radiopharmaceuticals (eg, strontium, samarium) within 8 weeks before first dose of study treatment administration.
• Prior surgery that requires general anesthesia must be completed at least 14 days before first dose of study treatment
• Adequate bone marrow, liver and kidney function

Exclusion Criteria:

• Uncontrolled or significant cardiac disease
• Any uncontrolled medical condition or psychiatric disorder including infection, autoimmune disease, bleeding disorder or symptomatic involvement of the central nervous system
• Treatment with any anti-cancer therapy or participation in another investigational drug or biologics trial within 28 days or ≤ 5 half-lives (whichever is shorter)
• Patients who discontinue prior immune-modulating therapies (including regimens containing an immune agonist or a PD-L1/PD-1 antagonist) due to toxicity or have received treatment within 5 half lives or 90 days
• Pregnancy or breastfeeding
• For patients participating in cohort expansion: Prior treatment with a CTLA-4 antagonist, including ipilimumab and tremelimumab

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: FPT155 monotherapy; The study consists of dose escalation and cohort expansions	Biological: FPT155; A soluble CD80 fusion protein
Experimental: FPT155 in combination with pembrolizumab; The study consists of dose escalation and cohort expansions	Biological: FPT155; A soluble CD80 fusion protein; Biological: pembrolizumab; An anti-PD1 antibody

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs)	TEAE was defined as an adverse event (AE) that was not present prior to the start date of study drug or was worsened during treatment and 100 days after last dose of treatment. An AE that was present at treatment initiation but resolved and then reappeared and the event severity increase while the participant was on treatment is also a TEAE. A severe AE (SAE) is defined as any untoward medical occurrence that at any dose: Is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, and is a congenital anomaly/birth defect. AEs were graded 1 (mild)-5 (fatal AE) according to the National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTCAE) Version 4.03.	Median (min, max) duration of FPT155 exposure was 6.57 [3.0, 49.6] weeks for the Phase 1a Monotherapy part of the study, 8.29 [3.0, 27.1] weeks for the Phase 1b Monotherapy, and 14.71 [3.0, 25.1] weeks for the Phase 1a Combination
Phase 1a Monotherapy: Number of Participants Who Experienced Dose Limiting Toxicities (DLTs)	DLTs ware defined as any of the events that occurred during the first 28 days of treatment and were assessed by the Clinical Research Coordinator (CRC) as related to FPT155.	Cycle 1 (one cycle = 21 days) Day 1 post-dose, up to approximately 21 days
Phase 1b Monotherapy: Number of Participants Who Had FPT155 Treatment Discontinued Due to AEs	Represents the number of participants who had discontinuation of FPT155 dosing due to AEs.	Median (min, max) duration of FPT155 exposure was 8.29 [3.0, 27.1] weeks.
Phase 1b Monotherapy: Number of Participants Who Had FPT155 Treatment Modified Due to AEs	Represents the number of participants who had a modification in the dosing schedules of FPT155 due to AEs.	Median (min, max) duration of FPT155 exposure was 8.29 [3.0, 27.1] weeks.
Phase 1b Monotherapy: Number of Participants Who Had FPT155 Treatment Interrupted Due to AEs	Represents the number of participants who had an interruption in the dosing schedules of FPT155 due to AEs.	Median (min, max) duration of FPT155 exposure was 8.29 [3.0, 27.1] weeks.
Phase 1a Combination: Number of Participants Who Experienced DLTs	DLTs ware defined as any of the events that occur during the first 28 days of treatment and are assessed by the CRC as related to FPT155.	Cycle 1 (one cycle = 21 days) Day 1 post-dose, up to approximately 21 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1a Monotherapy: Area Under Serum Concentration-time Profile From Time 0 to Time Tau (The Dosing Interval) (AUC0-tau) of FPT155		Cycle 1 (21-day cycles) Day 1 pre-dose, Day 1 (15min, 1h, 2h, 6h post-dose), Day 2, Day 4, Day 8, Day 15
Phase 1a Monotherapy: Maximum Observed Serum Concentration (Cmax) of FPT155		Cycle 1 (21-day cycles) Day 1 pre-dose, Day 1 (15min, 1h, 2h, 6h post-dose), Day 2, Day 4, Day 8, Day 15
Phase 1a Monotherapy: Trough Observed Serum Concentration at the End of Each Dose Interval (Ctrough) of FPT155		Cycle 1 (21-day cycles) Day 1 pre-dose, Day 1 (15min, 1h, 2h, 6h post-dose), Day 2, Day 4, Day 8, Day 15
Phase 1a Monotherapy: Clearance (CL) of FPT155		Cycle 1 (21-day cycles) Day 1 pre-dose, Day 1 (15min, 1h, 2h, 6h post-dose), Day 2, Day 4, Day 8, Day 15
Phase 1a Monotherapy: Terminal Half-life (t1/2) of FPT155		Cycle 1 (21-day cycles) Day 1 pre-dose, Day 1 (15min, 1h, 2h, 6h post-dose), Day 2, Day 4, Day 8, Day 15
Phase 1a Monotherapy: Volume of Distribution at Steady State (Vss) of FPT155		Cycle 1 (21-day cycles) Day 1 pre-dose, Day 1 (15min, 1h, 2h, 6h post-dose), Day 2, Day 4, Day 8, Day 15
Phase 1a Monotherapy: Number of Participants With Treatment-emergent Anti-FPT155 Antibody Response	Data presented below includes participants with at least 1 anti-drug antibodies-positive sample relative to baseline after initiation of the treatment.	Cycle 1 (21-day cycles) Day 1
Phase 1b Monotherapy: Objective Response Rate (ORR) Per RECIST v1.1	ORR was defined as the total number of participants with confirmed responses of either complete response (CR) (CR: The disappearance of all target lesions, any pathological lymph nodes [whether target or non-target] must have a reduction in short axis to <10 mm) or partial response (PR) (PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters), as determined by the investigator per RECIST v1.1.	Up to approximately 30 months
Phase 1b Monotherapy: Duration of Response (DOR) Per RECIST v1.1	DOR was defined as the time from first response (CR [The disappearance of all target lesions, any pathological lymph nodes {whether target or non-target} or PR [At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters] determined by the investigator per RECIST v1.1) that was subsequently confirmed until the onset of progressive disease (DP) (DP: At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study [this includes the baseline sum if that is the smallest on study]. In addition to the 20% relative increase, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression) or death from any cause, whichever occurred first.	Up to approximately 30 months
Phase 1b Monotherapy: Progression-free Survival (PFS) Per RECIST v1.1	PFS was defined as time from the first dose of study treatment until the first documentation by the investigator of DP (DP: At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study [this includes the baseline sum if that is the smallest on study]. In addition to the 20% relative increase, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression) per RECIST v1.1 or death from any cause, whichever occurred first. The median was estimated by using the Kaplan-Meier method and corresponding 2-sided 90% CI using Brookmeyer and Crowley methodology.	Up to approximately 30 months
Phase 1b Monotherapy: Disease Control Rate (DCR) Per RECIST v1.1	DCR was defined as the total number of participants with confirmed responses of either CR (CR: The disappearance of all target lesions, any pathological lymph nodes [whether target or non-target] must have a reduction in short axis to <10 mm), PR (PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters), or stable disease (SD) (SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. In numerical terms, it means a reduction in tumor size that is less than 30% [which is required for PR] and an increase in size that is less than 20% [which is required for PD]) as determined by the investigator per RECIST v1.1.	Up to approximately 30 months
Phase 1b Monotherapy: AUC0-tau of FPT155		Cycle 1 (21-day cycles) Day 1 pre-dose, Day 1 (15min, 1h, 2h, 6h post-dose), Day 2, Day 4, Day 8, Day 15
Phase 1b Monotherapy: Cmax of FPT155		Cycle 1 (21-day cycles) Day 1 pre-dose, Day 1 (15min, 1h, 2h, 6h post-dose), Day 2, Day 4, Day 8, Day 15
Phase 1b Monotherapy: Ctrough of FPT155		Cycle 1 (21-day cycles) Day 1 pre-dose, Day 1 (15min, 1h, 2h, 6h post-dose), Day 2, Day 4, Day 8, Day 15
Phase 1b Monotherapy: CL of FPT155		Cycle 1 (21-day cycles) Day 1 pre-dose, Day 1 (15min, 1h, 2h, 6h post-dose), Day 2, Day 4, Day 8, Day 15
Phase 1b Monotherapy: t1/2 of FPT155		Cycle 1 (21-day cycles) Day 1 pre-dose, Day 1 (15min, 1h, 2h, 6h post-dose), Day 2, Day 4, Day 8, Day 15
Phase 1b Monotherapy: Vss of FPT155		Cycle 1 (21-day cycles) Day 1 pre-dose, Day 1 (15min, 1h, 2h, 6h post-dose), Day 2, Day 4, Day 8, Day 15
Phase 1b Monotherapy: Number of Participants With Treatment-emergent Anti-FPT155 Antibody Response	Data presented below includes participants with at least 1 anti-drug antibodies-positive sample relative to baseline after initiation of the treatment.	Cycle 1 (21-day cycles) Day 1
Phase 1a Combination: ORR Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1	ORR was defined as the total number of participants with confirmed responses of either CR (CR: The disappearance of all target lesions, any pathological lymph nodes [whether target or non-target] must have a reduction in short axis to <10 mm) or PR (PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters), as determined by the investigator per RECIST v1.1.	Up to approximately 30 months

Collaborators and Investigators

• Sponsor: Five Prime Therapeutics, Inc.
• Investigators: Study Director: MD, Amgen

Study record dates

Study Major Dates

• Study Start (Actual): October 18, 2018
• Primary Completion (Actual): August 10, 2021
• Study Completion (Actual): August 10, 2021

Study Registration Dates

• First Submitted: August 13, 2019
• First Submitted That Met QC Criteria: August 28, 2019
• First Posted (Actual): August 30, 2019

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 4, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Pembrolizumab
• Other Study ID Numbers: FPT155-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No