Clinical trial NCT04074759: FPT155 in Patients With Advanced Solid Tumors
Official title: A Phase 1a/1b Study of FPT155 in Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Advanced Solid Tumors
Lead sponsor: Five Prime Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2019-08-30
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: Two arm trial with multiple cohorts
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs)
timeFrame: 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
measure: Phase 1a Monotherapy: Number of Participants Who Experienced Dose Limiting Toxicities (DLTs)
timeFrame: Cycle 1 (one cycle = 21 days) Day 1 post-dose, up to approximately 21 days
measure: Phase 1b Monotherapy: Number of Participants Who Had FPT155 Treatment Discontinued Due to AEs
timeFrame: Median (min, max) duration of FPT155 exposure was 8.29 [3.0, 27.1] weeks.
measure: Phase 1b Monotherapy: Number of Participants Who Had FPT155 Treatment Modified Due to AEs
timeFrame: Median (min, max) duration of FPT155 exposure was 8.29 [3.0, 27.1] weeks.
measure: Phase 1b Monotherapy: Number of Participants Who Had FPT155 Treatment Interrupted Due to AEs
timeFrame: Median (min, max) duration of FPT155 exposure was 8.29 [3.0, 27.1] weeks.
measure: Phase 1a Combination: Number of Participants Who Experienced DLTs
timeFrame: Cycle 1 (one cycle = 21 days) Day 1 post-dose, up to approximately 21 days
Secondary outcomes:
measure: Phase 1a Monotherapy: Area Under Serum Concentration-time Profile From Time 0 to Time Tau (The Dosing Interval) (AUC0-tau) of FPT155
timeFrame: 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
measure: Phase 1a Monotherapy: Maximum Observed Serum Concentration (Cmax) of FPT155
timeFrame: 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
measure: Phase 1a Monotherapy: Trough Observed Serum Concentration at the End of Each Dose Interval (Ctrough) of FPT155
timeFrame: 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
measure: Phase 1a Monotherapy: Clearance (CL) of FPT155
timeFrame: 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
measure: Phase 1a Monotherapy: Terminal Half-life (t1/2) of FPT155
timeFrame: 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
measure: Phase 1a Monotherapy: Volume of Distribution at Steady State (Vss) of FPT155
timeFrame: 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
measure: Phase 1a Monotherapy: Number of Participants With Treatment-emergent Anti-FPT155 Antibody Response
timeFrame: Cycle 1 (21-day cycles) Day 1
measure: Phase 1b Monotherapy: Objective Response Rate (ORR) Per RECIST v1.1
timeFrame: Up to approximately 30 months
measure: Phase 1b Monotherapy: Duration of Response (DOR) Per RECIST v1.1
timeFrame: Up to approximately 30 months
measure: Phase 1b Monotherapy: Progression-free Survival (PFS) Per RECIST v1.1
timeFrame: Up to approximately 30 months
measure: Phase 1b Monotherapy: Disease Control Rate (DCR) Per RECIST v1.1
timeFrame: Up to approximately 30 months
measure: Phase 1b Monotherapy: AUC0-tau of FPT155
timeFrame: 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
measure: Phase 1b Monotherapy: Cmax of FPT155
timeFrame: 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
measure: Phase 1b Monotherapy: Ctrough of FPT155
timeFrame: 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
measure: Phase 1b Monotherapy: CL of FPT155
timeFrame: 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
measure: Phase 1b Monotherapy: t1/2 of FPT155
timeFrame: 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
measure: Phase 1b Monotherapy: Vss of FPT155
timeFrame: 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
measure: Phase 1b Monotherapy: Number of Participants With Treatment-emergent Anti-FPT155 Antibody Response
timeFrame: Cycle 1 (21-day cycles) Day 1
measure: Phase 1a Combination: ORR Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
timeFrame: Up to approximately 30 months
Other outcomes:
Locations:
city: Camperdown
country: Australia
facility: Chris O'Brien Lifehouse
state: New South Wales
city: Darlinghurst
country: Australia
facility: St Vincent's Hospital Sydney
state: New South Wales
city: Randwick
country: Australia
facility: Scientia Clinical Research
state: New South Wales
city: Auchenflower
country: Australia
facility: ICON
state: Queensland
city: Heidelberg
country: Australia
facility: Olivia Newton-John Cancer Center
state: Victoria
city: Malvern
country: Australia
facility: Cabrini Hospital
state: Victoria
city: Nedlands
country: Australia
facility: Linear Clinical Research
state: Western Australia
city: Goyang-Si
country: Korea, Republic of
facility: National Cancer Center
state: Gyeonggi-do
city: Suwon-Si
country: Korea, Republic of
facility: St Vincent Hospital of the Catholic University of Korea
state: Gyeonggi-do
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References: