Advanced Solid Tumors, Breast Cancer, Endometrial Cancer, Ovarian Cancer
Conditions
Brief summary
This is a multi-center study to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and preliminary efficacy of FPA150, an anti-B7H4 antibody alone or in combination with pembrolizumab an anti-PD1 antibody in patients with advanced solid tumors. The Phase 1a, open-label, cohort will identify a recommended dose of FPA150 to use for Phase 1a Combination (FPA150 and Pembrolizumab) Safety Lead-in and for Phase 1b monotherapy cohorts.
Detailed description
This is a Phase 1a/1b open-label, multicenter study to evaluate the dosing, safety, tolerability, PK, pharmacodynamics, and preliminary efficacy of FPA150 as monotherapy and in combination with pembrolizumab, an anti-PD1 antibody, in patients with advanced solid tumors. This study includes a Phase 1a FPA150 Monotherapy Dose Escalation, Phase 1a Monotherapy Dose Exploration, Phase 1a combination Safety Lead-in (FPA150 + pembrolizumab), a Phase 1b FPA150 Monotherapy Dose Expansion, and a Phase 1b combination Dose Expansion (FPA150 + pembrolizumab). The Phase 1a Monotherapy Dose Escalation will include an initial accelerated titration design followed by a standard 3+3 dose escalation design until the MTD and/or RD for Phase 1b is determined. The Phase 1a combination Safety Lead-In will start enrolling once the FPA150 monotherapy RD is identified in Phase 1a monotherapy dose escalation and will continue until the FPA150 MTD/RD in combination is identified. Phase 1a FPA150 monotherapy Dose Exploration may include cohorts that may enroll beyond 3 patients whose tumors express high levels of B7-H4 protein and/or have varying levels of B7H4 expression including low (\<10% IHC 2+ or 3+ scores) or no expression on their tumor cells (up to 20 additional patients across all dose levels) to further evaluate safety, PK, pharmacodynamics, and clinical activity at that dose (to be conditional upon the dose level clearing DLT criteria). Phase 1b will be the Dose Expansion (monotherapy and combination) portion of the study. Enrollment into Phase 1b Dose Expansion will begin after identification of the MTD and/or RD in Phase 1a (monotherapy and Safety Lead-in). Preliminary efficacy will be evaluated in Phase 1b in planned expansion cohorts that include patients with specific tumor types that are B7-H4+ advanced solid tumors.
Interventions
BIOLOGICALFPA150
A monoclonal antibody against B7-H4
BIOLOGICALPembrolizumab
An anti-PD1 antibody
Sponsors
Five Prime Therapeutics, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Single arm trial with multiple cohorts
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
(Phase 1a Monotherapy and Combination Therapy): * Histologically confirmed solid tumors except primary central nervous system (CNS) tumors. * Disease that is unresectable, locally advanced, or metastatic. * Patients must have had progressive disease during or after, or refused, appropriate standard therapy for their tumor type. * All patients must have at least one measurable lesion at baseline according to RECIST v1.1; tumor sites situated in a previously irradiated area, or in an area subjected to other loco-regional therapy, are not considered measurable unless there has been demonstrated progression in the lesion. * Adequate washout for prior anti-cancer therapy (ie, ≥ 5 half-lives or 4 weeks since the last dose, whichever is shorter). * Availability of archival tumor tissue and consent to providing archival tumor for retrospective biomarker analysis, or willingness to undergo a fresh tumor biopsy during screening (a biopsy is required for patients in the Phase 1a Dose Exploration portion). * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. * Prior radiotherapy must be completed at least 2 weeks before the first dose of study drug. * Prior radiopharmaceuticals (eg strontium, samarium) must be completed at least 8 weeks before the first dose of study drug. * Prior surgery requiring general anesthesia must be completed one week before first study drug administration. Surgery requiring local/epidural must be completed at least 72 hours before first study drug administration. * Screening laboratory values must meet the following criteria: * Neutrophils ≥ 1200 cells/ µL * Platelets ≥ 75 × 103/ µL * Hemoglobin (Hb) ≥ 9.0 g/dL * Serum creatinine \< 1.5× ULN or creatinine clearance (CrCl) of ≥ 40 mL/ minute * AST and ALT \< 3× ULN (\<5ULN in patients with liver metastases) * Bilirubin \< 1.5× ULN (except patients with Gilbert's syndrome, who must have total bilirubin \< 3 mg/dL) * For Phase 1a Combination Safety Lead-in Patients ONLY: * B7-H4 positive ovarian cancer * or cytologically confirmed diagnosis of recurrent epithelial ovarian, primary peritoneal, or fallopian tube carcinoma that is refractory to existing therapy(ies) known to provide clinical benefit * Progressive disease on or after at least two prior regimens of treatment including at least one platinum-containing regimen, or unable to tolerate additional chemotherapy * No prior therapy with an anti-PD1 or PD-L1-directed agent Inclusion Criteria (Phase 1b monotherapy and combination): * All Inclusion Criteria for Phase 1a (Exception: Phase 1a Inclusion Criterion #1). * Positive for B7-H4 expression in an archival or fresh tumor sample as evaluated by an accompanying validated central laboratory IHC assay. Archival tissue for patients enrolled in Cohort 1b1 (Breast Cancer) must be within 24 months prior to pre-screening. * History of other malignancy is permitted provided it has been definitively treated with no evidence of recurrence within the past 2 years (Exception: Definitively treated non-melanoma skin cancer, lobular cancer in situ, and cervical cancer in situ within 2 years are permitted). Cohort Specific Phase 1b Criteria (monotherapy and combination therapy) Breast Cancer Cohorts: TNBC: * Histologically or cytologically confirmed metastatic TNBC * At least two prior lines of systemic chemotherapy with at least one being administered in the metastatic setting HR+ Breast: * Histologically or cytologically confirmed metastatic HR+ breast carcinoma * Patients must have received at least two prior lines of hormonal therapy * Patients must have received at least one prior line of systemic chemotherapy (in the adjuvant or metastatic setting) Ovarian Cancer (monotherapy): * Histologically or cytologically confirmed diagnosis of recurrent epithelial ovarian, primary peritoneal, or fallopian tube carcinoma that is refractory to existing * Progressive disease on or after at least two prior regimens of treatment including at least one platinum-containing regimen, or unable to tolerate additional chemotherapy Endometrial Cancer: * Histologically or cytologically confirmed recurrent or persistent endometrial cancer that is refractory to curative or established treatments * Progressive disease on or after at least one prior regimen of systemic chemotherapy, or unable to tolerate systemic chemotherapy Ovarian Cancer (combination): Histologically or cytologically confirmed diagnosis of recurrent epithelial ovarian, primary peritoneal, or fallopian tube carcinoma that is refractory to existing * Progressive disease on or after at least two prior regimens of treatment including at least one platinum-containing regimen, or unable to tolerate additional chemotherapy * No prior therapy with an anti-PD1 or PD-L1-directed agent
Exclusion criteria
* Immunosuppressive doses of systemic medications, such as steroids or absorbed topical steroids (doses \> 10 mg/day prednisone or equivalent daily) must be discontinued at least 2 weeks before the first dose of study drug. Short courses of high dose steroids or continuous low dose (prednisone \< 10 mg/day ) are allowed. * Decreased cardiac function with New York Heart Association (NYHA) \> Class 2 at screening. * Uncontrolled or significant heart disorder such as unstable angina. * QT interval corrected for heart rate (QTc) per institutional guidelines \> 450 msec for males or \> 470 msec for females at screening. * Current unresolved infection or history of chronic, active, clinically significant infection (viral, bacterial, fungal, or other) which, in the opinion of the Investigator, would preclude the patient from exposure to a biologic agent or may pose a risk to patient safety. * Any uncontrolled medical condition or psychiatric disorder which, in the opinion of the Investigator, would pose a risk to patient safety or interfere with study participation or interpretation of individual patient results. * Active, known, or suspected autoimmune disease. Patients with Type I diabetes mellitus, hypothyroidism requiring only hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger, are permitted to enroll. * Known history of testing positive for human immunodeficiency virus (HIV) 1 or 2 or known acquired immunodeficiency syndrome (AIDS). * Positive test for hepatitis B virus surface antigen (HBsAg) or detectable hepatitis C virus ribonucleic acid (HCV RNA) indicating acute or chronic infection. * Ongoing adverse effects from prior treatment \> Grade 1 (with the exception of Grade 2 alopecia or peripheral neuropathy) based on National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE). * Symptomatic interstitial lung disease or inflammatory pneumonitis. * Untreated or active CNS or leptomeningeal metastases. Patients are eligible if metastases have been treated and patients are neurologically returned to baseline or neurologically stable (except for residual signs or symptoms related to the CNS treatment) for at least 2 weeks before the first dose of study drug. * Evidence of coagulopathy or bleeding diathesis. Patients receiving stable therapeutic doses of anti-coagulants will be permitted. * Transfusion of blood or platelets completed within 72 hours before the first dose of study drug. * Any uncontrolled inflammatory GI disease including Crohn's Disease and ulcerative colitis * For Cohort 1b1 only: Patients with HER2 positive disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1a Monotherapy: Number of Participants Experiencing Grade 3 and Grade 4 Adverse Events (AEs) | From day 1 up to 28 days after last dose (median [min, max] treatment duration= 9.143 [3.00, 52.00] weeks) | An AE is defined as any untoward medical occurrence in a participant or clinical investigation subject that was administered a pharmaceutical product, which does not necessarily have to have a causal relationship with this treatment. Grade 3 and 4 severity ratings were defined as follows: Grade 3: Severe or medically significant but non-immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living; severe AE Grade 4: Life-threatening consequences; urgent intervention indicated |
| Phase 1a Monotherapy: Number of Participants Experiencing Dose Limiting Toxicities (DLTs) | Up to 21 days | DLTs were defined as any of the following events regardless of attribution (except for those events clearly due to the underlying disease or extraneous causes): Any Grade 3 or higher non-hematologic toxicity (except Grade 3 nausea, vomiting, and diarrhea) that occurred within the first 21 days of treatment. Grade 3 nausea, vomiting, diarrhea lasting \>72 hours, that occurred within the first 21 days of treatment. Febrile neutropenia and/or documented infection, Grade 4 neutropenia that lasted more than 7 days, Grade 4 thrombocytopenia, or Grade 3 thrombocytopenia accompanied by bleeding within first 21 days of treatment. Aspartate aminotransferase (AST) / alanine transaminase (ALT) \>3 × upper limit of normal (ULN) and concurrent total bilirubin \> 2 × ULN that was not related to liver involvement with cancer. Other Grade 3 laboratory values that did not resolve within 72 hours. Any Grade 4 laboratory value regardless of clinical sequelae |
| Phase 1a Monotherapy: Number of Participants Experiencing Treatment-emergent Adverse Events (TEAEs) | From day 1 up to 28 days after last dose (median [min, max] treatment duration= 9.143 [3.00, 52.00] weeks) | TEAEs were defined as an AE that began or worsened in severity after at least one dose of study treatment (FPA150) had been administered. Clinically significant laboratory abnormalities and ECG abnormalities are included as TEAEs. |
| Phase 1b Monotherapy: Number of Participants Experiencing AEs | From day 1 up to 28 days after last dose (median [min, max] treatment duration= 6.35 [3.00, 108.14] weeks) | An AE is defined as any untoward medical occurrence in a participant or clinical investigation subject that was administered a pharmaceutical product, which does not necessarily have to have a causal relationship with this treatment. A serious AE is defined as any AE that resulted in death, was life threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital abnormality/birth defect or important medical events. Clinically significant laboratory abnormalities and ECG abnormalities were included as TEAEs. |
| Phase 1a Combination Safety Lead-In & Phase 1b Combination: Number of Participants Experiencing AEs | From day 1 up to 28 days after last dose (median [min, max] treatment duration= 12.00 [6.00, 36.43] weeks) | An AE is defined as any untoward medical occurrence in a participant or clinical investigation subject that was administered a pharmaceutical product, which does not necessarily have to have a causal relationship with this treatment. A serious AE is defined as any AE that results in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital abnormality/birth defect or important medical events that do not meet the preceding criteria but based on appropriate medical judgment may jeopardize the participant or may require medical or surgical intervention to prevent any of the outcomes listed above. |
| Phase 1a Combination Safety Lead-In & Phase 1b Combination: Number of Participants Experiencing Grade 3 and Grade 4 AEs | From day 1 up to 28 days after last dose (median [min, max] treatment duration= 12.00 [6.00, 36.43] weeks) | An AE is defined as any untoward medical occurrence in a participant or clinical investigation subject that was administered a pharmaceutical product, which does not necessarily have to have a causal relationship with this treatment. A serious AE is defined as any AE that results in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital abnormality/birth defect or important medical events that do not meet the preceding criteria but based on appropriate medical judgment may jeopardize the participant or may require medical or surgical intervention to prevent any of the outcomes listed above. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1b Monotherapy: Progression-free Survival (PFS) Per RECIST v1.1 | Up to approximately 24 months | PFS defined as time from the first dose of study treatment until the first documentation by the investigator of disease progression per RECIST v1.1 or death from any cause, whichever comes first. Patients who were alive and progression-free at the time of data analysis were censored at the time of their last assessment for tumor response. |
| Phase 1b Combination: PFS Per RECIST v1.1 | Up to approximately 24 months | PFS defined as time from the first dose of study treatment until the first documentation by the investigator of disease progression per RECIST v1.1 or death from any cause, whichever comes first. Patients who were alive and progression-free at the time of data analysis were censored at the time of their last assessment for tumor response. |
| Phase 1b Combination: ORR Per RECIST v1.1 | Up to approximately 24 months | ORR was defined as the percentage of participants who achieved best overall response (BOR) of either complete response (CR) or partial response (PR) based on investigator assessment of tumor lesions per RECIST v1.1. The BOR was the best response documented from first dose until the end of study, first disease progression, death, or start of new anti-cancer therapy, whichever was earlier. |
| Phase 1b Combination: DOR Per RECIST v1.1 | Up to approximately 24 months | DOR is defined as the time from first onset of response (CR or PR determined by the investigator per RECIST v1.1) that is subsequently confirmed until the onset of progressive disease or death from any cause, whichever comes first. Patients who were alive and progression-free at the time of data analysis were censored at the time of their last assessment for tumor response. DOR was estimated using the Kaplan-Meier method. |
| Phase 1a Monotherapy: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of FPA150 | Cycle 1 (cycle = 21 days) day 1 pre-dose, 15min and 4h post-dose, day 2 (24h), day 4 (72h), day 8 (168h) post-dose, and day 15. Cycle 2, 3, 4 ,5 ,7, 9, day 1 pre-dose, day 1 (15min) post-dose. After cycle 9, day 1 every 4th dose (12 weeks) up to 52 weeks | FPA150 concentration in serum was determined using an enzyme linked immunosorbent assay (ELISA) method and the PK parameters were derived from serum FPA150 concentration-time data using non-compartment analysis. |
| Phase 1a Monotherapy: Time to Reach Maximum Serum Concentration (Tmax) of FPA150 | Cycle 1 (cycle = 21 days) day 1 pre-dose, 15min and 4h post-dose, day 2 (24h), day 4 (72h), day 8 (168h) post-dose, and day 15. Cycle 2, 3, 4 ,5 ,7, 9, day 1 pre-dose, day 1 (15min) post-dose. After cycle 9, day 1 every 4th dose (12 weeks) up to 52 weeks | — |
| Phase 1a Monotherapy: Terminal Half-Life (T1/2) of FPA150 | Cycle 1 (cycle = 21 days) day 1 pre-dose, 15min and 4h post-dose, day 2 (24h), day 4 (72h), day 8 (168h) post-dose, and day 15. Cycle 2, 3, 4 ,5 ,7, 9, day 1 pre-dose, day 1 (15min) post-dose. After cycle 9, day 1 every 4th dose (12 weeks) up to 52 weeks | — |
| Phase 1a Monotherapy: Trough Serum Concentration (Ctrough) of FPA150 | Cycle 1 (cycle = 21 days) day 1 pre-dose, 15min and 4h post-dose, day 2 (24h), day 4 (72h), day 8 (168h) post-dose, and day 15. Cycle 2, 3, 4 ,5 ,7, 9, day 1 pre-dose, day 1 (15min) post-dose. After cycle 9, day 1 every 4th dose (12 weeks) up to 52 weeks | — |
| Phase 1b Monotherapy: AUClast of FPA150 | Cycle 1 (one cycle = 21 days) day 1 pre-dose, day 1 15min and 4h post-dose, day 2 (24h), day 4 (72h), day 8 (168h) post-dose, and day 15. Cycle 2, 3, 4 ,5 ,7, 9, day 1 pre-dose, day 1 (15min) post-dose. After cycle 9, day 1 every 4th dose (12 weeks) | — |
| Phase 1b Monotherapy: Time to Reach Cmax of FPA150 | Cycle 1 (cycle = 21 days) day 1 pre-dose, 15min and 4h post-dose, day 2 (24h), day 4 (72h), day 8 (168h) post-dose, and day 15. Cycle 2, 3, 4 ,5 ,7, 9, day 1 pre-dose, day 1 (15min) post-dose. After cycle 9, day 1 every 4th dose (12 weeks) up to 108 weeks | — |
| Phase 1b Monotherapy: Cmax of FPA150 | Cycle 1 (cycle = 21 days) day 1 pre-dose, 15min and 4h post-dose, day 2 (24h), day 4 (72h), day 8 (168h) post-dose, and day 15. Cycle 2, 3, 4 ,5 ,7, 9, day 1 pre-dose, day 1 (15min) post-dose. After cycle 9, day 1 every 4th dose (12 weeks) up to 108 weeks | — |
| Phase 1b Monotherapy: Cthrough of FPA150 | Cycle 1 (cycle = 21 days) day 1 pre-dose, 15min and 4h post-dose, day 2 (24h), day 4 (72h), day 8 (168h) post-dose, and day 15. Cycle 2, 3, 4 ,5 ,7, 9, day 1 pre-dose, day 1 (15min) post-dose. After cycle 9, day 1 every 4th dose (12 weeks) up to 108 weeks | — |
| Phase 1b Monotherapy: T1/2 of FPA150 in Days | Cycle 1 (cycle = 21 days) day 1 pre-dose, 15min and 4h post-dose, day 2 (24h), day 4 (72h), day 8 (168h) post-dose, and day 15. Cycle 2, 3, 4 ,5 ,7, 9, day 1 pre-dose, day 1 (15min) post-dose. After cycle 9, day 1 every 4th dose (12 weeks) up to 108 weeks | — |
| Phase 1a Monotherapy: Maximum Serum Concentration (Cmax) of FPA150 | Cycle 1 (cycle = 21 days) day 1 pre-dose, 15min and 4h post-dose, day 2 (24h), day 4 (72h), day 8 (168h) post-dose, and day 15. Cycle 2, 3, 4 ,5 ,7, 9, day 1 pre-dose, day 1 (15min) post-dose. After cycle 9, day 1 every 4th dose (12 weeks) up to 52 weeks | — |
| Phase 1a Monotherapy: Number of Participants With ADAs to FPA150 | From day 1 up to 28 days after last dose (median [min, max] treatment duration= 9.143 [3.00, 52.00] weeks) | All ADA samples were collected prior to dosing. A baseline ADA-positive patient was defined as a patient who had an ADA positive sample at baseline. Postbaseline treatment induced ADA positive is derived as participants with ADA negative at baseline and ADA positive at any postbaseline timepoint, or ADA positive at baseline and ADA positive with titer of at least 4-fold of the baseline titer at one or more postbaseline timepoint. |
| Phase 1b Monotherapy: Number of Participants With ADAs to FPA150 at Baseline | Cycle 1 day 1 pre-dose (baseline) | All ADA samples were collected prior to dosing. A baseline ADA-positive patient was defined as a patient who had an ADA positive sample at baseline. Postbaseline treatment induced ADA positive is derived as participants with ADA negative at baseline and ADA positive at any postbaseline timepoint, or ADA positive at baseline and ADA positive with titer of at least 4-fold of the baseline titer at one or more postbaseline timepoint. |
| Phase 1b Monotherapy: Number of Participants With ADAs to FPA150 Postbaseline | From day 1 up to 28 days after last dose (median [min, max] treatment duration= 6.35 [3.00, 108.14] weeks) | All ADA samples were collected prior to dosing. A baseline ADA-positive patient was defined as a patient who had an ADA positive sample at baseline. Postbaseline treatment induced ADA positive is derived as participants with ADA negative at baseline and ADA positive at any postbaseline timepoint, or ADA positive at baseline and ADA positive with titer of at least 4-fold of the baseline titer at one or more postbaseline timepoint. |
| Phase 1b Monotherapy: Overall Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) | Up to approximately 24 months | ORR was defined as the percentage of participants who achieved best overall response (BOR) of either complete response (CR) or partial response (PR) based on investigator assessment of tumor lesions per RECIST v1.1. The BOR was the best response documented from first dose until the end of study, first disease progression, death, or start of new anti-cancer therapy, whichever was earlier. |
| Phase 1b Monotherapy: Duration of Response (DOR) Per RECIST v1.1 | Up to approximately 24 months | DOR is defined as the time from first onset of response (CR or PR determined by the investigator per RECIST v1.1) that is subsequently confirmed until the onset of progressive disease or death from any cause, whichever comes first. Patients who were alive and progression-free at the time of data analysis were censored at the time of their last assessment for tumor response. DOR was estimated using the Kaplan-Meier method. |
Countries
South Korea, United States
Participant flow
Recruitment details
Participants were enrolled at 25 study centers in the United Studies and the Republic of Korea, and participated from 27 March 2018 to 21 April 2021.
Participants by arm
| Arm | Count |
|---|---|
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose A Participants with advanced solid tumors received FPA150 once every 3 weeks (Q3W) in escalating doses (Dose A-H) until the maximum tolerated dose (MTD) and/or recommended dose (RD) for Phase 1b was determined. | 1 |
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose B Participants with advanced solid tumors received FPA150 Q3W in escalating doses until MTD and/or RD for Phase 1b was determined. | 1 |
| Phase 1a Monotherapy Dose Escalation + Exploration Dose C Participants with advanced solid tumors received FPA150 Q3W in escalating doses until MTD and/or RD for Phase 1b was determined. | 3 |
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose D Participants with advanced solid tumors received FPA150 Q3W in escalating doses until MTD and/or RD for Phase 1b was determined. | 1 |
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose E Participants with advanced solid tumors received FPA150 Q3W in escalating doses until MTD and/or RD for Phase 1b was determined. | 3 |
| Phase 1a Monotherapy Dose Escalation + Exploration Dose F Participants with advanced solid tumors received FPA150 Q3W in escalating doses until MTD and/or RD for Phase 1b was determined. | 8 |
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose G Participants with advanced solid tumors received FPA150 Q3W in escalating doses until MTD and/or RD for Phase 1b was determined. | 8 |
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose H Participants with advanced solid tumors received FPA150 Q3W in escalating doses until MTD and/or RD for Phase 1b was determined. | 4 |
| Phase 1b Monotherapy FPA150 Dose H Participants with breast, ovarian, or endometrial cancer received FPA150 MTD/RD. | 54 |
| Phase 1a Combination Safety Lead-In & Phase 1b Combination FPA150 Dose H & Pembrolizumab 200 mg Participants with ovarian cancer received FPA 150 Dose H in combination with pembrolizumab 200 mg IV Q3W during the Phase 1a Safety Lead-in. Participants with ovarian cancer in the Phase 1b Combination received FPA 150 Dose H in combination with pembrolizumab 200 mg IV Q3W. | 12 |
| Total | 95 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Death | 0 | 0 | 0 | 0 | 0 | 3 | 2 | 1 | 26 | 3 |
| Overall Study | Investigator decision | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Lost to Follow-up | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Other | 0 | 1 | 1 | 0 | 1 | 2 | 3 | 2 | 7 | 3 |
| Overall Study | Study termination by Sponsor | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 11 | 3 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 1 | 2 | 1 | 1 | 7 | 2 |
Baseline characteristics
| Characteristic | Total | Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose B | Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose A | Phase 1a Monotherapy Dose Escalation + Exploration Dose C | Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose D | Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose E | Phase 1a Monotherapy Dose Escalation + Exploration Dose F | Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose G | Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose H | Phase 1b Monotherapy FPA150 Dose H | Phase 1a Combination Safety Lead-In & Phase 1b Combination FPA150 Dose H & Pembrolizumab 200 mg |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 41 Participants | 1 Participants | 0 Participants | 2 Participants | 0 Participants | 2 Participants | 4 Participants | 4 Participants | 1 Participants | 21 Participants | 6 Participants |
| Age, Categorical Between 18 and 65 years | 54 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 4 Participants | 4 Participants | 3 Participants | 33 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 89 Participants | 0 Participants | 1 Participants | 2 Participants | 1 Participants | 3 Participants | 7 Participants | 7 Participants | 3 Participants | 53 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 16 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 13 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 72 Participants | 1 Participants | 0 Participants | 3 Participants | 1 Participants | 3 Participants | 8 Participants | 6 Participants | 2 Participants | 38 Participants | 10 Participants |
| Sex: Female, Male Female | 88 Participants | 1 Participants | 1 Participants | 2 Participants | 1 Participants | 2 Participants | 5 Participants | 7 Participants | 3 Participants | 54 Participants | 12 Participants |
| Sex: Female, Male Male | 7 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 3 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 1 | 0 / 1 | 0 / 3 | 0 / 1 | 0 / 3 | 3 / 8 | 2 / 8 | 1 / 4 | 9 / 21 | 10 / 17 | 7 / 16 | 3 / 12 |
| other Total, other adverse events | 1 / 1 | 1 / 1 | 3 / 3 | 1 / 1 | 3 / 3 | 7 / 8 | 7 / 8 | 4 / 4 | 16 / 21 | 14 / 17 | 16 / 16 | 11 / 12 |
| serious Total, serious adverse events | 1 / 1 | 0 / 1 | 0 / 3 | 0 / 1 | 1 / 3 | 1 / 8 | 3 / 8 | 0 / 4 | 3 / 21 | 6 / 17 | 5 / 16 | 3 / 12 |
Outcome results
Primary
Phase 1a Combination Safety Lead-In & Phase 1b Combination: Number of Participants Experiencing AEs
An AE is defined as any untoward medical occurrence in a participant or clinical investigation subject that was administered a pharmaceutical product, which does not necessarily have to have a causal relationship with this treatment. A serious AE is defined as any AE that results in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital abnormality/birth defect or important medical events that do not meet the preceding criteria but based on appropriate medical judgment may jeopardize the participant or may require medical or surgical intervention to prevent any of the outcomes listed above.
Time frame: From day 1 up to 28 days after last dose (median [min, max] treatment duration= 12.00 [6.00, 36.43] weeks)
Population: SAS: All participants who have received any portion of at least one dose of FPA150.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose A | Phase 1a Combination Safety Lead-In & Phase 1b Combination: Number of Participants Experiencing AEs | 11 Participants |
Primary
Phase 1a Combination Safety Lead-In & Phase 1b Combination: Number of Participants Experiencing Grade 3 and Grade 4 AEs
An AE is defined as any untoward medical occurrence in a participant or clinical investigation subject that was administered a pharmaceutical product, which does not necessarily have to have a causal relationship with this treatment. A serious AE is defined as any AE that results in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital abnormality/birth defect or important medical events that do not meet the preceding criteria but based on appropriate medical judgment may jeopardize the participant or may require medical or surgical intervention to prevent any of the outcomes listed above.
Time frame: From day 1 up to 28 days after last dose (median [min, max] treatment duration= 12.00 [6.00, 36.43] weeks)
Population: SAS: All participants who have received any portion of at least one dose of FPA150.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose A | Phase 1a Combination Safety Lead-In & Phase 1b Combination: Number of Participants Experiencing Grade 3 and Grade 4 AEs | 4 Participants |
Primary
Phase 1a Monotherapy: Number of Participants Experiencing Dose Limiting Toxicities (DLTs)
DLTs were defined as any of the following events regardless of attribution (except for those events clearly due to the underlying disease or extraneous causes): Any Grade 3 or higher non-hematologic toxicity (except Grade 3 nausea, vomiting, and diarrhea) that occurred within the first 21 days of treatment. Grade 3 nausea, vomiting, diarrhea lasting \>72 hours, that occurred within the first 21 days of treatment. Febrile neutropenia and/or documented infection, Grade 4 neutropenia that lasted more than 7 days, Grade 4 thrombocytopenia, or Grade 3 thrombocytopenia accompanied by bleeding within first 21 days of treatment. Aspartate aminotransferase (AST) / alanine transaminase (ALT) \>3 × upper limit of normal (ULN) and concurrent total bilirubin \> 2 × ULN that was not related to liver involvement with cancer. Other Grade 3 laboratory values that did not resolve within 72 hours. Any Grade 4 laboratory value regardless of clinical sequelae
Time frame: Up to 21 days
Population: SAS: All participants who have received any portion of at least one dose of FPA150.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose A | Phase 1a Monotherapy: Number of Participants Experiencing Dose Limiting Toxicities (DLTs) | 0 Participants |
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose B | Phase 1a Monotherapy: Number of Participants Experiencing Dose Limiting Toxicities (DLTs) | 0 Participants |
| Phase 1a Monotherapy Dose Escalation + Exploration Dose C | Phase 1a Monotherapy: Number of Participants Experiencing Dose Limiting Toxicities (DLTs) | 0 Participants |
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose D | Phase 1a Monotherapy: Number of Participants Experiencing Dose Limiting Toxicities (DLTs) | 0 Participants |
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose E | Phase 1a Monotherapy: Number of Participants Experiencing Dose Limiting Toxicities (DLTs) | 0 Participants |
| Phase 1a Monotherapy Dose Escalation + Exploration Dose F | Phase 1a Monotherapy: Number of Participants Experiencing Dose Limiting Toxicities (DLTs) | 0 Participants |
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose G | Phase 1a Monotherapy: Number of Participants Experiencing Dose Limiting Toxicities (DLTs) | 0 Participants |
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose H | Phase 1a Monotherapy: Number of Participants Experiencing Dose Limiting Toxicities (DLTs) | 0 Participants |
Primary
Phase 1a Monotherapy: Number of Participants Experiencing Grade 3 and Grade 4 Adverse Events (AEs)
An AE is defined as any untoward medical occurrence in a participant or clinical investigation subject that was administered a pharmaceutical product, which does not necessarily have to have a causal relationship with this treatment. Grade 3 and 4 severity ratings were defined as follows: Grade 3: Severe or medically significant but non-immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living; severe AE Grade 4: Life-threatening consequences; urgent intervention indicated
Time frame: From day 1 up to 28 days after last dose (median [min, max] treatment duration= 9.143 [3.00, 52.00] weeks)
Population: SAS: All participants who have received any portion of at least one dose of FPA150.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose A | Phase 1a Monotherapy: Number of Participants Experiencing Grade 3 and Grade 4 Adverse Events (AEs) | 1 Participants |
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose B | Phase 1a Monotherapy: Number of Participants Experiencing Grade 3 and Grade 4 Adverse Events (AEs) | 1 Participants |
| Phase 1a Monotherapy Dose Escalation + Exploration Dose C | Phase 1a Monotherapy: Number of Participants Experiencing Grade 3 and Grade 4 Adverse Events (AEs) | 3 Participants |
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose D | Phase 1a Monotherapy: Number of Participants Experiencing Grade 3 and Grade 4 Adverse Events (AEs) | 1 Participants |
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose E | Phase 1a Monotherapy: Number of Participants Experiencing Grade 3 and Grade 4 Adverse Events (AEs) | 1 Participants |
| Phase 1a Monotherapy Dose Escalation + Exploration Dose F | Phase 1a Monotherapy: Number of Participants Experiencing Grade 3 and Grade 4 Adverse Events (AEs) | 4 Participants |
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose G | Phase 1a Monotherapy: Number of Participants Experiencing Grade 3 and Grade 4 Adverse Events (AEs) | 5 Participants |
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose H | Phase 1a Monotherapy: Number of Participants Experiencing Grade 3 and Grade 4 Adverse Events (AEs) | 1 Participants |
Primary
Phase 1a Monotherapy: Number of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)
TEAEs were defined as an AE that began or worsened in severity after at least one dose of study treatment (FPA150) had been administered. Clinically significant laboratory abnormalities and ECG abnormalities are included as TEAEs.
Time frame: From day 1 up to 28 days after last dose (median [min, max] treatment duration= 9.143 [3.00, 52.00] weeks)
Population: SAS: All participants who have received any portion of at least one dose of FPA150.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose A | Phase 1a Monotherapy: Number of Participants Experiencing Treatment-emergent Adverse Events (TEAEs) | 1 Participants |
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose B | Phase 1a Monotherapy: Number of Participants Experiencing Treatment-emergent Adverse Events (TEAEs) | 1 Participants |
| Phase 1a Monotherapy Dose Escalation + Exploration Dose C | Phase 1a Monotherapy: Number of Participants Experiencing Treatment-emergent Adverse Events (TEAEs) | 3 Participants |
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose D | Phase 1a Monotherapy: Number of Participants Experiencing Treatment-emergent Adverse Events (TEAEs) | 1 Participants |
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose E | Phase 1a Monotherapy: Number of Participants Experiencing Treatment-emergent Adverse Events (TEAEs) | 3 Participants |
| Phase 1a Monotherapy Dose Escalation + Exploration Dose F | Phase 1a Monotherapy: Number of Participants Experiencing Treatment-emergent Adverse Events (TEAEs) | 7 Participants |
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose G | Phase 1a Monotherapy: Number of Participants Experiencing Treatment-emergent Adverse Events (TEAEs) | 7 Participants |
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose H | Phase 1a Monotherapy: Number of Participants Experiencing Treatment-emergent Adverse Events (TEAEs) | 4 Participants |
Primary
Phase 1b Monotherapy: Number of Participants Experiencing AEs
An AE is defined as any untoward medical occurrence in a participant or clinical investigation subject that was administered a pharmaceutical product, which does not necessarily have to have a causal relationship with this treatment. A serious AE is defined as any AE that resulted in death, was life threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital abnormality/birth defect or important medical events. Clinically significant laboratory abnormalities and ECG abnormalities were included as TEAEs.
Time frame: From day 1 up to 28 days after last dose (median [min, max] treatment duration= 6.35 [3.00, 108.14] weeks)
Population: SAS: All participants who have received any portion of at least one dose of FPA150.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose A | Phase 1b Monotherapy: Number of Participants Experiencing AEs | Endometrial Cancer | 16 Participants |
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose A | Phase 1b Monotherapy: Number of Participants Experiencing AEs | Breast Cancer | 18 Participants |
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose A | Phase 1b Monotherapy: Number of Participants Experiencing AEs | Ovarian Cancer | 16 Participants |
Secondary
Phase 1a Monotherapy: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of FPA150
FPA150 concentration in serum was determined using an enzyme linked immunosorbent assay (ELISA) method and the PK parameters were derived from serum FPA150 concentration-time data using non-compartment analysis.
Time frame: Cycle 1 (cycle = 21 days) day 1 pre-dose, 15min and 4h post-dose, day 2 (24h), day 4 (72h), day 8 (168h) post-dose, and day 15. Cycle 2, 3, 4 ,5 ,7, 9, day 1 pre-dose, day 1 (15min) post-dose. After cycle 9, day 1 every 4th dose (12 weeks) up to 52 weeks
Population: PK Analysis Population: All participants who received at least one dose of FPA150 and had at least one FPA150 serum concentration result. Only participants with available data are included. Participants with available data are included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose A | Phase 1a Monotherapy: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of FPA150 | 0.7591 day*µg/mL | — |
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose B | Phase 1a Monotherapy: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of FPA150 | 9.2670 day*µg/mL | — |
| Phase 1a Monotherapy Dose Escalation + Exploration Dose C | Phase 1a Monotherapy: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of FPA150 | 8.2148 day*µg/mL | Standard Deviation 0.21781 |
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose D | Phase 1a Monotherapy: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of FPA150 | 37.4379 day*µg/mL | — |
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose E | Phase 1a Monotherapy: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of FPA150 | 136.6567 day*µg/mL | Standard Deviation 38.99659 |
| Phase 1a Monotherapy Dose Escalation + Exploration Dose F | Phase 1a Monotherapy: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of FPA150 | 407.1698 day*µg/mL | Standard Deviation 69.78823 |
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose G | Phase 1a Monotherapy: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of FPA150 | 1376.0347 day*µg/mL | Standard Deviation 411.93171 |
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose H | Phase 1a Monotherapy: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of FPA150 | 2468.4741 day*µg/mL | Standard Deviation 638.37831 |
Secondary
Phase 1a Monotherapy: Maximum Serum Concentration (Cmax) of FPA150
Time frame: Cycle 1 (cycle = 21 days) day 1 pre-dose, 15min and 4h post-dose, day 2 (24h), day 4 (72h), day 8 (168h) post-dose, and day 15. Cycle 2, 3, 4 ,5 ,7, 9, day 1 pre-dose, day 1 (15min) post-dose. After cycle 9, day 1 every 4th dose (12 weeks) up to 52 weeks
Population: PK Analysis Population: All participants who received at least one dose of FPA150 and had at least one FPA150 serum concentration result. Only participants with available data are included. Participants with available data are included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose A | Phase 1a Monotherapy: Maximum Serum Concentration (Cmax) of FPA150 | 0.0521 μg/mL | — |
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose B | Phase 1a Monotherapy: Maximum Serum Concentration (Cmax) of FPA150 | 0.2146 μg/mL | — |
| Phase 1a Monotherapy Dose Escalation + Exploration Dose C | Phase 1a Monotherapy: Maximum Serum Concentration (Cmax) of FPA150 | 0.0549 μg/mL | Standard Deviation 0.00184 |
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose D | Phase 1a Monotherapy: Maximum Serum Concentration (Cmax) of FPA150 | 0.0556 μg/mL | — |
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose E | Phase 1a Monotherapy: Maximum Serum Concentration (Cmax) of FPA150 | 0.0998 μg/mL | Standard Deviation 0.09405 |
| Phase 1a Monotherapy Dose Escalation + Exploration Dose F | Phase 1a Monotherapy: Maximum Serum Concentration (Cmax) of FPA150 | 0.0523 μg/mL | Standard Deviation 0.01107 |
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose G | Phase 1a Monotherapy: Maximum Serum Concentration (Cmax) of FPA150 | 0.1449 μg/mL | Standard Deviation 0.08381 |
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose H | Phase 1a Monotherapy: Maximum Serum Concentration (Cmax) of FPA150 | 0.0892 μg/mL | Standard Deviation 0.07284 |
Secondary
Phase 1a Monotherapy: Number of Participants With ADAs to FPA150
All ADA samples were collected prior to dosing. A baseline ADA-positive patient was defined as a patient who had an ADA positive sample at baseline. Postbaseline treatment induced ADA positive is derived as participants with ADA negative at baseline and ADA positive at any postbaseline timepoint, or ADA positive at baseline and ADA positive with titer of at least 4-fold of the baseline titer at one or more postbaseline timepoint.
Time frame: From day 1 up to 28 days after last dose (median [min, max] treatment duration= 9.143 [3.00, 52.00] weeks)
Population: ADA Analysis Set: The ADA Analysis Set included all enrolled participants who received at least 1 dose of FPA150 and had at least 1 ADA sample drawn at any timepoint.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose A | Phase 1a Monotherapy: Number of Participants With ADAs to FPA150 | Postbaseline | ADA Negative | 1 Participants |
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose A | Phase 1a Monotherapy: Number of Participants With ADAs to FPA150 | Baseline | ADA Negative | 1 Participants |
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose A | Phase 1a Monotherapy: Number of Participants With ADAs to FPA150 | Postbaseline | Not Evaluable | 0 Participants |
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose A | Phase 1a Monotherapy: Number of Participants With ADAs to FPA150 | Postbaseline | ADA Positive | 0 Participants |
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose A | Phase 1a Monotherapy: Number of Participants With ADAs to FPA150 | Baseline | ADA Positive | 0 Participants |
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose A | Phase 1a Monotherapy: Number of Participants With ADAs to FPA150 | Baseline | Not Evaluable | 0 Participants |
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose B | Phase 1a Monotherapy: Number of Participants With ADAs to FPA150 | Baseline | Not Evaluable | 0 Participants |
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose B | Phase 1a Monotherapy: Number of Participants With ADAs to FPA150 | Baseline | ADA Negative | 1 Participants |
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose B | Phase 1a Monotherapy: Number of Participants With ADAs to FPA150 | Postbaseline | ADA Positive | 0 Participants |
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose B | Phase 1a Monotherapy: Number of Participants With ADAs to FPA150 | Postbaseline | Not Evaluable | 0 Participants |
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose B | Phase 1a Monotherapy: Number of Participants With ADAs to FPA150 | Baseline | ADA Positive | 0 Participants |
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose B | Phase 1a Monotherapy: Number of Participants With ADAs to FPA150 | Postbaseline | ADA Negative | 1 Participants |
| Phase 1a Monotherapy Dose Escalation + Exploration Dose C | Phase 1a Monotherapy: Number of Participants With ADAs to FPA150 | Baseline | Not Evaluable | 0 Participants |
| Phase 1a Monotherapy Dose Escalation + Exploration Dose C | Phase 1a Monotherapy: Number of Participants With ADAs to FPA150 | Postbaseline | ADA Positive | 0 Participants |
| Phase 1a Monotherapy Dose Escalation + Exploration Dose C | Phase 1a Monotherapy: Number of Participants With ADAs to FPA150 | Baseline | ADA Positive | 1 Participants |
| Phase 1a Monotherapy Dose Escalation + Exploration Dose C | Phase 1a Monotherapy: Number of Participants With ADAs to FPA150 | Baseline | ADA Negative | 2 Participants |
| Phase 1a Monotherapy Dose Escalation + Exploration Dose C | Phase 1a Monotherapy: Number of Participants With ADAs to FPA150 | Postbaseline | ADA Negative | 3 Participants |
| Phase 1a Monotherapy Dose Escalation + Exploration Dose C | Phase 1a Monotherapy: Number of Participants With ADAs to FPA150 | Postbaseline | Not Evaluable | 0 Participants |
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose D | Phase 1a Monotherapy: Number of Participants With ADAs to FPA150 | Baseline | ADA Negative | 1 Participants |
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose D | Phase 1a Monotherapy: Number of Participants With ADAs to FPA150 | Baseline | Not Evaluable | 0 Participants |
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose D | Phase 1a Monotherapy: Number of Participants With ADAs to FPA150 | Postbaseline | Not Evaluable | 0 Participants |
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose D | Phase 1a Monotherapy: Number of Participants With ADAs to FPA150 | Postbaseline | ADA Negative | 1 Participants |
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose D | Phase 1a Monotherapy: Number of Participants With ADAs to FPA150 | Postbaseline | ADA Positive | 0 Participants |
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose D | Phase 1a Monotherapy: Number of Participants With ADAs to FPA150 | Baseline | ADA Positive | 0 Participants |
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose E | Phase 1a Monotherapy: Number of Participants With ADAs to FPA150 | Postbaseline | ADA Positive | 0 Participants |
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose E | Phase 1a Monotherapy: Number of Participants With ADAs to FPA150 | Baseline | ADA Positive | 0 Participants |
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose E | Phase 1a Monotherapy: Number of Participants With ADAs to FPA150 | Baseline | Not Evaluable | 0 Participants |
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose E | Phase 1a Monotherapy: Number of Participants With ADAs to FPA150 | Baseline | ADA Negative | 3 Participants |
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose E | Phase 1a Monotherapy: Number of Participants With ADAs to FPA150 | Postbaseline | ADA Negative | 2 Participants |
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose E | Phase 1a Monotherapy: Number of Participants With ADAs to FPA150 | Postbaseline | Not Evaluable | 1 Participants |
| Phase 1a Monotherapy Dose Escalation + Exploration Dose F | Phase 1a Monotherapy: Number of Participants With ADAs to FPA150 | Baseline | ADA Negative | 3 Participants |
| Phase 1a Monotherapy Dose Escalation + Exploration Dose F | Phase 1a Monotherapy: Number of Participants With ADAs to FPA150 | Postbaseline | ADA Negative | 3 Participants |
| Phase 1a Monotherapy Dose Escalation + Exploration Dose F | Phase 1a Monotherapy: Number of Participants With ADAs to FPA150 | Postbaseline | Not Evaluable | 0 Participants |
| Phase 1a Monotherapy Dose Escalation + Exploration Dose F | Phase 1a Monotherapy: Number of Participants With ADAs to FPA150 | Baseline | ADA Positive | 0 Participants |
| Phase 1a Monotherapy Dose Escalation + Exploration Dose F | Phase 1a Monotherapy: Number of Participants With ADAs to FPA150 | Postbaseline | ADA Positive | 0 Participants |
| Phase 1a Monotherapy Dose Escalation + Exploration Dose F | Phase 1a Monotherapy: Number of Participants With ADAs to FPA150 | Baseline | Not Evaluable | 0 Participants |
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose G | Phase 1a Monotherapy: Number of Participants With ADAs to FPA150 | Postbaseline | Not Evaluable | 1 Participants |
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose G | Phase 1a Monotherapy: Number of Participants With ADAs to FPA150 | Postbaseline | ADA Negative | 4 Participants |
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose G | Phase 1a Monotherapy: Number of Participants With ADAs to FPA150 | Baseline | ADA Positive | 0 Participants |
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose G | Phase 1a Monotherapy: Number of Participants With ADAs to FPA150 | Postbaseline | ADA Positive | 0 Participants |
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose G | Phase 1a Monotherapy: Number of Participants With ADAs to FPA150 | Baseline | ADA Negative | 4 Participants |
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose G | Phase 1a Monotherapy: Number of Participants With ADAs to FPA150 | Baseline | Not Evaluable | 1 Participants |
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose H | Phase 1a Monotherapy: Number of Participants With ADAs to FPA150 | Postbaseline | Not Evaluable | 0 Participants |
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose H | Phase 1a Monotherapy: Number of Participants With ADAs to FPA150 | Baseline | Not Evaluable | 0 Participants |
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose H | Phase 1a Monotherapy: Number of Participants With ADAs to FPA150 | Postbaseline | ADA Positive | 1 Participants |
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose H | Phase 1a Monotherapy: Number of Participants With ADAs to FPA150 | Baseline | ADA Positive | 0 Participants |
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose H | Phase 1a Monotherapy: Number of Participants With ADAs to FPA150 | Baseline | ADA Negative | 4 Participants |
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose H | Phase 1a Monotherapy: Number of Participants With ADAs to FPA150 | Postbaseline | ADA Negative | 3 Participants |
Secondary
Phase 1a Monotherapy: Terminal Half-Life (T1/2) of FPA150
Time frame: Cycle 1 (cycle = 21 days) day 1 pre-dose, 15min and 4h post-dose, day 2 (24h), day 4 (72h), day 8 (168h) post-dose, and day 15. Cycle 2, 3, 4 ,5 ,7, 9, day 1 pre-dose, day 1 (15min) post-dose. After cycle 9, day 1 every 4th dose (12 weeks) up to 52 weeks
Population: Cycle 1 (cycle = 21 days) day 1 pre-dose, 15min and 4h post-dose, day 2 (24h), day 4 (72h), day 8 (168h) post-dose, and day 15. Cycle 2, 3, 4 ,5 ,7, 9, day 1 pre-dose, day 1 (15min) post-dose. After cycle 9, day 1 every 4th dose (12 weeks) up to 52 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose A | Phase 1a Monotherapy: Terminal Half-Life (T1/2) of FPA150 | 2.7207 day | — |
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose B | Phase 1a Monotherapy: Terminal Half-Life (T1/2) of FPA150 | 7.2128 day | — |
| Phase 1a Monotherapy Dose Escalation + Exploration Dose C | Phase 1a Monotherapy: Terminal Half-Life (T1/2) of FPA150 | 4.6081 day | Standard Deviation 0.99726 |
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose D | Phase 1a Monotherapy: Terminal Half-Life (T1/2) of FPA150 | 8.3932 day | — |
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose E | Phase 1a Monotherapy: Terminal Half-Life (T1/2) of FPA150 | 10.4675 day | Standard Deviation 3.25703 |
| Phase 1a Monotherapy Dose Escalation + Exploration Dose F | Phase 1a Monotherapy: Terminal Half-Life (T1/2) of FPA150 | 13.0391 day | Standard Deviation 4.7422 |
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose G | Phase 1a Monotherapy: Terminal Half-Life (T1/2) of FPA150 | 8.3539 day | Standard Deviation 2.80118 |
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose H | Phase 1a Monotherapy: Terminal Half-Life (T1/2) of FPA150 | 9.1097 day | Standard Deviation 1.25064 |
Secondary
Phase 1a Monotherapy: Time to Reach Maximum Serum Concentration (Tmax) of FPA150
Time frame: Cycle 1 (cycle = 21 days) day 1 pre-dose, 15min and 4h post-dose, day 2 (24h), day 4 (72h), day 8 (168h) post-dose, and day 15. Cycle 2, 3, 4 ,5 ,7, 9, day 1 pre-dose, day 1 (15min) post-dose. After cycle 9, day 1 every 4th dose (12 weeks) up to 52 weeks
Population: PK Analysis Population: All participants who received at least one dose of FPA150 and had at least one FPA150 serum concentration result. Only participants with available data are included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose A | Phase 1a Monotherapy: Time to Reach Maximum Serum Concentration (Tmax) of FPA150 | 0.0521 Days | — |
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose B | Phase 1a Monotherapy: Time to Reach Maximum Serum Concentration (Tmax) of FPA150 | 0.2146 Days | — |
| Phase 1a Monotherapy Dose Escalation + Exploration Dose C | Phase 1a Monotherapy: Time to Reach Maximum Serum Concentration (Tmax) of FPA150 | 0.0549 Days | Standard Deviation 0.00184 |
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose D | Phase 1a Monotherapy: Time to Reach Maximum Serum Concentration (Tmax) of FPA150 | 0.0556 Days | — |
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose E | Phase 1a Monotherapy: Time to Reach Maximum Serum Concentration (Tmax) of FPA150 | 0.0998 Days | Standard Deviation 0.09405 |
| Phase 1a Monotherapy Dose Escalation + Exploration Dose F | Phase 1a Monotherapy: Time to Reach Maximum Serum Concentration (Tmax) of FPA150 | 0.0523 Days | Standard Deviation 0.01107 |
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose G | Phase 1a Monotherapy: Time to Reach Maximum Serum Concentration (Tmax) of FPA150 | 0.1449 Days | Standard Deviation 0.08381 |
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose H | Phase 1a Monotherapy: Time to Reach Maximum Serum Concentration (Tmax) of FPA150 | 0.0892 Days | Standard Deviation 0.07284 |
Secondary
Phase 1a Monotherapy: Trough Serum Concentration (Ctrough) of FPA150
Time frame: Cycle 1 (cycle = 21 days) day 1 pre-dose, 15min and 4h post-dose, day 2 (24h), day 4 (72h), day 8 (168h) post-dose, and day 15. Cycle 2, 3, 4 ,5 ,7, 9, day 1 pre-dose, day 1 (15min) post-dose. After cycle 9, day 1 every 4th dose (12 weeks) up to 52 weeks
Population: PK Analysis Population: All participants who received at least one dose of FPA150 and had at least one FPA150 serum concentration result. Only participants with available data are included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose A | Phase 1a Monotherapy: Trough Serum Concentration (Ctrough) of FPA150 | 0.0000 µg/mL | — |
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose B | Phase 1a Monotherapy: Trough Serum Concentration (Ctrough) of FPA150 | 0.1160 µg/mL | — |
| Phase 1a Monotherapy Dose Escalation + Exploration Dose C | Phase 1a Monotherapy: Trough Serum Concentration (Ctrough) of FPA150 | 0.0000 µg/mL | Standard Deviation 0 |
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose D | Phase 1a Monotherapy: Trough Serum Concentration (Ctrough) of FPA150 | 0.6050 µg/mL | — |
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose E | Phase 1a Monotherapy: Trough Serum Concentration (Ctrough) of FPA150 | 3.0825 µg/mL | Standard Deviation 2.18567 |
| Phase 1a Monotherapy Dose Escalation + Exploration Dose F | Phase 1a Monotherapy: Trough Serum Concentration (Ctrough) of FPA150 | 9.5243 µg/mL | Standard Deviation 5.17826 |
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose G | Phase 1a Monotherapy: Trough Serum Concentration (Ctrough) of FPA150 | 30.5385 µg/mL | Standard Deviation 7.13748 |
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose H | Phase 1a Monotherapy: Trough Serum Concentration (Ctrough) of FPA150 | 37.9028 µg/mL | Standard Deviation 4.28708 |
Secondary
Phase 1b Combination: DOR Per RECIST v1.1
DOR is defined as the time from first onset of response (CR or PR determined by the investigator per RECIST v1.1) that is subsequently confirmed until the onset of progressive disease or death from any cause, whichever comes first. Patients who were alive and progression-free at the time of data analysis were censored at the time of their last assessment for tumor response. DOR was estimated using the Kaplan-Meier method.
Time frame: Up to approximately 24 months
Population: No DOR data for Phase 1b combination was collected due to study early termination. Data for phase 1a were considered exploratory.
Secondary
Phase 1b Combination: ORR Per RECIST v1.1
ORR was defined as the percentage of participants who achieved best overall response (BOR) of either complete response (CR) or partial response (PR) based on investigator assessment of tumor lesions per RECIST v1.1. The BOR was the best response documented from first dose until the end of study, first disease progression, death, or start of new anti-cancer therapy, whichever was earlier.
Time frame: Up to approximately 24 months
Population: No ORR data for Phase 1b combination was collected due to study early termination. Data for phase 1a were considered exploratory.
Secondary
Phase 1b Combination: PFS Per RECIST v1.1
PFS defined as time from the first dose of study treatment until the first documentation by the investigator of disease progression per RECIST v1.1 or death from any cause, whichever comes first. Patients who were alive and progression-free at the time of data analysis were censored at the time of their last assessment for tumor response.
Time frame: Up to approximately 24 months
Population: No PFS data for Phase 1b combination was collected due to study early termination. Data for phase 1a were considered exploratory.
Secondary
Phase 1b Monotherapy: AUClast of FPA150
Time frame: Cycle 1 (one cycle = 21 days) day 1 pre-dose, day 1 15min and 4h post-dose, day 2 (24h), day 4 (72h), day 8 (168h) post-dose, and day 15. Cycle 2, 3, 4 ,5 ,7, 9, day 1 pre-dose, day 1 (15min) post-dose. After cycle 9, day 1 every 4th dose (12 weeks)
Population: PK Analysis Population: All participants who received at least one dose of FPA150 and had at least one FPA150 serum concentration result.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose A | Phase 1b Monotherapy: AUClast of FPA150 | Breast Cancer | 2415.8123 Day*µg/mL | Standard Deviation 951.56795 |
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose A | Phase 1b Monotherapy: AUClast of FPA150 | Ovarian Cancer | 2664.4820 Day*µg/mL | Standard Deviation 761.1955 |
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose A | Phase 1b Monotherapy: AUClast of FPA150 | Endometrial Cancer | 2785.3974 Day*µg/mL | Standard Deviation 941.95867 |
Secondary
Phase 1b Monotherapy: Cmax of FPA150
Time frame: Cycle 1 (cycle = 21 days) day 1 pre-dose, 15min and 4h post-dose, day 2 (24h), day 4 (72h), day 8 (168h) post-dose, and day 15. Cycle 2, 3, 4 ,5 ,7, 9, day 1 pre-dose, day 1 (15min) post-dose. After cycle 9, day 1 every 4th dose (12 weeks) up to 108 weeks
Population: PK Analysis Population: All participants who received at least one dose of FPA150 and had at least one FPA150 serum concentration result.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose A | Phase 1b Monotherapy: Cmax of FPA150 | Breast Cancer | 383.8841 µg/mL | Standard Deviation 89.76028 |
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose A | Phase 1b Monotherapy: Cmax of FPA150 | Ovarian Cancer | 422.5332 µg/mL | Standard Deviation 101.20218 |
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose A | Phase 1b Monotherapy: Cmax of FPA150 | Endometrial Cancer | 456.9944 µg/mL | Standard Deviation 101.87663 |
Secondary
Phase 1b Monotherapy: Cthrough of FPA150
Time frame: Cycle 1 (cycle = 21 days) day 1 pre-dose, 15min and 4h post-dose, day 2 (24h), day 4 (72h), day 8 (168h) post-dose, and day 15. Cycle 2, 3, 4 ,5 ,7, 9, day 1 pre-dose, day 1 (15min) post-dose. After cycle 9, day 1 every 4th dose (12 weeks) up to 108 weeks
Population: PK Analysis Population: All participants who received at least one dose of FPA150 and had at least one FPA150 serum concentration result.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose A | Phase 1b Monotherapy: Cthrough of FPA150 | Breast Cancer | 57.6900 µg/mL | Standard Deviation 37.24538 |
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose A | Phase 1b Monotherapy: Cthrough of FPA150 | Ovarian Cancer | 56.1074 µg/mL | Standard Deviation 27.88026 |
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose A | Phase 1b Monotherapy: Cthrough of FPA150 | Endometrial Cancer | 72.1686 µg/mL | Standard Deviation 78.21933 |
Secondary
Phase 1b Monotherapy: Duration of Response (DOR) Per RECIST v1.1
DOR is defined as the time from first onset of response (CR or PR determined by the investigator per RECIST v1.1) that is subsequently confirmed until the onset of progressive disease or death from any cause, whichever comes first. Patients who were alive and progression-free at the time of data analysis were censored at the time of their last assessment for tumor response. DOR was estimated using the Kaplan-Meier method.
Time frame: Up to approximately 24 months
Population: Efficacy-Evaluable Analysis Set: included all participants that received at least 1 dose of FPA150, had at least 1 postbaseline evaluable tumor assessment unless death or clinical progressive disease occurred prior to the first post baseline disease assessment. Only responders have been included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose A | Phase 1b Monotherapy: Duration of Response (DOR) Per RECIST v1.1 | NA months |
Secondary
Phase 1b Monotherapy: Number of Participants With ADAs to FPA150 at Baseline
All ADA samples were collected prior to dosing. A baseline ADA-positive patient was defined as a patient who had an ADA positive sample at baseline. Postbaseline treatment induced ADA positive is derived as participants with ADA negative at baseline and ADA positive at any postbaseline timepoint, or ADA positive at baseline and ADA positive with titer of at least 4-fold of the baseline titer at one or more postbaseline timepoint.
Time frame: Cycle 1 day 1 pre-dose (baseline)
Population: ADA Analysis Set: The ADA Analysis Set included all enrolled participants who received at least 1 dose of FPA150 and had at least 1 ADA sample drawn at any timepoint.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose A | Phase 1b Monotherapy: Number of Participants With ADAs to FPA150 at Baseline | Breast Cancer | 1 Participants |
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose A | Phase 1b Monotherapy: Number of Participants With ADAs to FPA150 at Baseline | Ovarian Cancer | 1 Participants |
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose A | Phase 1b Monotherapy: Number of Participants With ADAs to FPA150 at Baseline | Endometrial Cancer | 1 Participants |
Secondary
Phase 1b Monotherapy: Number of Participants With ADAs to FPA150 Postbaseline
All ADA samples were collected prior to dosing. A baseline ADA-positive patient was defined as a patient who had an ADA positive sample at baseline. Postbaseline treatment induced ADA positive is derived as participants with ADA negative at baseline and ADA positive at any postbaseline timepoint, or ADA positive at baseline and ADA positive with titer of at least 4-fold of the baseline titer at one or more postbaseline timepoint.
Time frame: From day 1 up to 28 days after last dose (median [min, max] treatment duration= 6.35 [3.00, 108.14] weeks)
Population: ADA Analysis Set: The ADA Analysis Set included all enrolled participants who received at least 1 dose of FPA150 and had at least 1 ADA sample drawn at any timepoint.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose A | Phase 1b Monotherapy: Number of Participants With ADAs to FPA150 Postbaseline | Breast Cancer | 0 Participants |
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose A | Phase 1b Monotherapy: Number of Participants With ADAs to FPA150 Postbaseline | Ovarian Cancer | 1 Participants |
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose A | Phase 1b Monotherapy: Number of Participants With ADAs to FPA150 Postbaseline | Endometrial Cancer | 1 Participants |
Secondary
Phase 1b Monotherapy: Overall Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
ORR was defined as the percentage of participants who achieved best overall response (BOR) of either complete response (CR) or partial response (PR) based on investigator assessment of tumor lesions per RECIST v1.1. The BOR was the best response documented from first dose until the end of study, first disease progression, death, or start of new anti-cancer therapy, whichever was earlier.
Time frame: Up to approximately 24 months
Population: Efficacy-Evaluable Analysis Set: included all participants that received at least 1 dose of FPA150, had at least 1 postbaseline evaluable tumor assessment unless death or clinical progressive disease occurred prior to the first post baseline disease assessment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose A | Phase 1b Monotherapy: Overall Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) | Breast Cancer | 0 Participants |
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose A | Phase 1b Monotherapy: Overall Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) | Ovarian Cancer | 1 Participants |
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose A | Phase 1b Monotherapy: Overall Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) | Endometrial Cancer | 0 Participants |
Secondary
Phase 1b Monotherapy: Progression-free Survival (PFS) Per RECIST v1.1
PFS defined as time from the first dose of study treatment until the first documentation by the investigator of disease progression per RECIST v1.1 or death from any cause, whichever comes first. Patients who were alive and progression-free at the time of data analysis were censored at the time of their last assessment for tumor response.
Time frame: Up to approximately 24 months
Population: Efficacy-Evaluable Analysis Set: included all participants that received at least 1 dose of FPA150, had at least 1 postbaseline evaluable tumor assessment unless death or clinical progressive disease occurred prior to the first post baseline disease assessment.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose A | Phase 1b Monotherapy: Progression-free Survival (PFS) Per RECIST v1.1 | 1.40 months |
Secondary
Phase 1b Monotherapy: T1/2 of FPA150 in Days
Time frame: Cycle 1 (cycle = 21 days) day 1 pre-dose, 15min and 4h post-dose, day 2 (24h), day 4 (72h), day 8 (168h) post-dose, and day 15. Cycle 2, 3, 4 ,5 ,7, 9, day 1 pre-dose, day 1 (15min) post-dose. After cycle 9, day 1 every 4th dose (12 weeks) up to 108 weeks
Population: PK Analysis Population: All participants who received at least one dose of FPA150 and had at least one FPA150 serum concentration result.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose A | Phase 1b Monotherapy: T1/2 of FPA150 in Days | Breast Cancer | 9.3232 day | Standard Deviation 2.63376 |
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose A | Phase 1b Monotherapy: T1/2 of FPA150 in Days | Ovarian Cancer | 10.0294 day | Standard Deviation 3.90951 |
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose A | Phase 1b Monotherapy: T1/2 of FPA150 in Days | Endometrial Cancer | 7.9802 day | Standard Deviation 3.72524 |
Secondary
Phase 1b Monotherapy: Time to Reach Cmax of FPA150
Time frame: Cycle 1 (cycle = 21 days) day 1 pre-dose, 15min and 4h post-dose, day 2 (24h), day 4 (72h), day 8 (168h) post-dose, and day 15. Cycle 2, 3, 4 ,5 ,7, 9, day 1 pre-dose, day 1 (15min) post-dose. After cycle 9, day 1 every 4th dose (12 weeks) up to 108 weeks
Population: PK Analysis Population: All participants who received at least one dose of FPA150 and had at least one FPA150 serum concentration result.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose A | Phase 1b Monotherapy: Time to Reach Cmax of FPA150 | Breast Cancer | 0.0944 day | Standard Deviation 0.06325 |
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose A | Phase 1b Monotherapy: Time to Reach Cmax of FPA150 | Ovarian Cancer | 0.1056 day | Standard Deviation 0.06988 |
| Phase 1a Monotherapy Dose Escalation + Exploration FPA150 Dose A | Phase 1b Monotherapy: Time to Reach Cmax of FPA150 | Endometrial Cancer | 1.2803 day | Standard Deviation 4.71147 |