FPT155 in Patients With Advanced Solid Tumors
- Conditions
- Advanced Solid Tumors
- Interventions
- Registration Number
- NCT04074759
- Lead Sponsor
- Five Prime Therapeutics, Inc.
- 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 80
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description FPT155 monotherapy FPT155 The study consists of dose escalation and cohort expansions FPT155 in combination with pembrolizumab FPT155 The study consists of dose escalation and cohort expansions FPT155 in combination with pembrolizumab pembrolizumab The study consists of dose escalation and cohort expansions
- Primary Outcome Measures
Name Time Method Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) 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 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.
Phase 1a Monotherapy: Number of Participants Who Experienced Dose Limiting Toxicities (DLTs) Cycle 1 (one cycle = 21 days) Day 1 post-dose, up to approximately 21 days 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.
Phase 1b Monotherapy: Number of Participants Who Had FPT155 Treatment Discontinued Due to AEs Median (min, max) duration of FPT155 exposure was 8.29 [3.0, 27.1] weeks. Represents the number of participants who had discontinuation of FPT155 dosing due to AEs.
Phase 1b Monotherapy: Number of Participants Who Had FPT155 Treatment Modified Due to AEs Median (min, max) duration of FPT155 exposure was 8.29 [3.0, 27.1] weeks. Represents the number of participants who had a modification in the dosing schedules of FPT155 due to AEs.
Phase 1b Monotherapy: Number of Participants Who Had FPT155 Treatment Interrupted Due to AEs Median (min, max) duration of FPT155 exposure was 8.29 [3.0, 27.1] weeks. Represents the number of participants who had an interruption in the dosing schedules of FPT155 due to AEs.
Phase 1a Combination: Number of Participants Who Experienced DLTs Cycle 1 (one cycle = 21 days) Day 1 post-dose, up to approximately 21 days 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.
- Secondary Outcome Measures
Name Time Method 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 Cycle 1 (21-day cycles) Day 1 Data presented below includes participants with at least 1 anti-drug antibodies-positive sample relative to baseline after initiation of the treatment.
Phase 1b Monotherapy: Objective Response Rate (ORR) Per RECIST v1.1 Up to approximately 30 months 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.
Phase 1b Monotherapy: Duration of Response (DOR) Per RECIST v1.1 Up to approximately 30 months 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.
Phase 1b Monotherapy: Progression-free Survival (PFS) Per RECIST v1.1 Up to approximately 30 months 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.
Phase 1b Monotherapy: Disease Control Rate (DCR) Per RECIST v1.1 Up to approximately 30 months 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.
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 Cycle 1 (21-day cycles) Day 1 Data presented below includes participants with at least 1 anti-drug antibodies-positive sample relative to baseline after initiation of the treatment.
Phase 1a Combination: ORR Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 Up to approximately 30 months 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.
Trial Locations
- Locations (12)
Scientia Clinical Research
🇦🇺Randwick, New South Wales, Australia
Chris O'Brien Lifehouse
🇦🇺Camperdown, New South Wales, Australia
St Vincent's Hospital Sydney
🇦🇺Darlinghurst, New South Wales, Australia
ICON
🇦🇺Auchenflower, Queensland, Australia
Olivia Newton-John Cancer Center
🇦🇺Heidelberg, Victoria, Australia
Cabrini Hospital
🇦🇺Malvern, Victoria, Australia
Linear Clinical Research
🇦🇺Nedlands, Western Australia, Australia
National Cancer Center
🇰🇷Goyang-Si, Gyeonggi-do, Korea, Republic of
St Vincent Hospital of the Catholic University of Korea
🇰🇷Suwon-Si, Gyeonggi-do, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Severance Hospital, Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of