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A Study of FWD1509 in Adults With Non-Small Cell Lung Cancer (FWD1509)

Primary Purpose

Carcinoma, Non-Small-Cell Lung

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
FWD1509 MsOH
Sponsored by
Forward Pharmaceuticals Co., Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Carcinoma, Non-Small-Cell Lung focused on measuring FWD1509 MsOH in advanced non-small cell lung cancer, Forward Pharma, Forward, FWD1509, NSCLC, MsOH, FWD-001, First-in-human, Non-small cell lung cancer, Advanced solid malignancies, Solid malignancies, Solid tumor, EGFR, EGFR ex20ins, EGFR mutation, TKI, HER2

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Key Inclusion Criteria: Study-Wide Eligibility (Across All Study Parts):

A subject will be eligible for inclusion in this study only if all of the following criteria apply.

  1. Have histologically or cytologically confirmed locally advanced or metastatic NSCLC (Stage IIIB/IIIC or IV) [JACC edition 8], and inclusion of Stage IIIB only if not a candidate for curative therapy
  2. Must have sufficient tumor tissue (either archived sample or recent biopsy) available for analysis:

    1. Phase 1 Dose-escalation part: EGFR and HER2 mutations (including but not limited toL858R, exon 19 deletion, T790M, ex20ins, 21exon, G719X, S768I, L861Q, etc. for EGFR and A775YVMG, C776insVC, P780ins GSP etc. for HER2) should be confirmed by previously documented evidence or central lab
    2. Patients with both EGFR and HER2 mutations may be included in the dose escalation phase
    3. Phase 1 Dose-expansion part and Phase 2: Have an EGFR in-frame exon 20 insertion test by any central lab
  3. Must have at least one measurable lesion as defined by response evaluation criteria in solid tumors (RECIST v1.1)
  4. Prior anti-cancer therapies:

    1. Previously treated with one or more regimens of systemic therapy for locally advanced or metastatic disease
    2. Disease progressed or intolerant to at least one line of systematic therapies including but not limited to any EGFR-target therapies or immunotherapies, for metastatic / local relapsed settings
  5. Male or female adult participants (aged 18 years or older, or as defined per local regulations)
  6. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1
  7. Minimum life expectancy of 3 months or more
  8. Adequate organ function at baseline

    1. Bone marrow function

      • Absolute neutrophil count (ANC)≥1.5 x 10^9/L
      • Platelets ≥100 x 10^9/L
      • Hemoglobin ≥9 g/dL, criteria must be met without a transfusion within 2 weeks of the blood draw
    2. Hepatic function

      • AST and ALT ≤3 x upper limit of normal (ULN); if liver metastases, then ≤ 5 x ULN
      • Bilirubin ≤1.5 x ULN or ≤3 x ULN in the presence of documented Gilbert's Syndrome
    3. Renal function

      • Creatinine clearance ≥50 ml/min (calculated by Cockcroft and Gault equation (Cockcroft DW, 1976) (Appendix 3)
  9. Willingness and ability to comply with scheduled visits and study procedures

Exclusion Criteria:

A subject will be not eligible for inclusion in this study if any of the following criteria apply:

  1. Received anticancer therapy including cytotoxic chemotherapy, biological products and investigational agents, ≤ 21 days prior to first dose of FWD1509 MsOH; or received prior EGFR TKIs (e.g., gefitinib, erlotinib or osimertinib) ≤7 days prior to the first dose FWD1509 MsOH
  2. Have been diagnosed with another primary malignancy other than NSCLC except for patients with adequately treated non-melanoma skin cancer, cervical cancer in situ or definitively treated non-metastatic prostate cancer, or participants with another primary malignancy who are definitively relapse-free with at least 3 years elapsed since the diagnosis of the other primary malignancy
  3. Received radiotherapy ≤14 days prior to the first dose of FWD1509 MsOH or have not recovered from radiotherapy-related toxicities; palliative radiation administered outside the chest and brain, stereotactic radiosurgery (SRS), and stereotactic body radiotherapy are allowed up to 7 days prior to the first dose of FWD1509 MsOH
  4. Received strong CYP3A inhibitors and inducers within 2 weeks prior to the first dose of FWD1509 MsOH; they should be discontinued at least 2 weeks prior to the first dose of FWD1509 MsOH and avoided throughout the study duration (see Appendix 6)
  5. Received concomitant medications (e.g., statins) which are substrates of BCRP, p-glycoprotein or OATP1B1/1B3 (dose escalation part of phase 1 study)
  6. Have undergone major surgery within 28 days prior to first dose of FWD1509 MsOH. Minor surgical procedures, such as catheter placement or minimally invasive biopsy, are allowed
  7. Brain Metastasis: Have known active brain metastases (have either previously untreated intracranial CNS metastases or previously treated intracranial CNS metastases with radiologically documented new or progressing CNS lesions), except for the following conditions

    1. Brain metastases are allowed if they have been treated with surgery and/or radiation and have been stable without requiring corticosteroids to control symptoms within 7 days before the first dose of FWD1509 MsOH and have no evidence of new or enlarging brain metastases
    2. Requiring corticosteroids to control symptoms within 7 days prior to the first dose of FWD1509 MsOH or during study period; patients previously treated for CNS metastases who are clinically stable, have no new lesions, and who do not need treatment with a corticosteroid within the 7 days before the first dose of FWD1509 MsOH and during study period are allowed to be enrolled
  8. Have current spinal cord compression (symptomatic or asymptomatic and detected by radiographic imaging) or leptomeningeal disease (symptomatic or asymptomatic)
  9. Have significant, uncontrolled, or active cardiovascular disease
  10. QCc-related criteria:

    1. A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval >480 milliseconds (ms) (CTCAE grade 1) using Fredericia's QT correction formula
    2. A history of additional risk factors for Torsades de Pointes (TdP) (e.g., heart failure, hypokalemia, family history of Long QT Syndrome
  11. Have significant, uncontrolled, or active renal disease
  12. Have a known history of uncontrolled hypertension (per institution practice); participants with hypertension should be under treatment on study entry to control blood pressure
  13. Have any abnormal changes in the cornea or retina that may increase the risk of ocular toxicity during screening
  14. Have an ongoing or active infection, including but not limited to, the requirement for intravenous (IV) antibiotics, or a known history of human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV). Testing is not required in the absence of history
  15. Currently have or have a history of interstitial lung disease, radiation pneumonitis that required steroid treatment, or drug-related pneumonitis
  16. Female participants who are lactating and breastfeeding or have a positive urine or serum pregnancy test during the screening period
  17. Have gastrointestinal illness or disorder that could affect oral absorption of FWD1509 MsOH
  18. Have any condition or illness that, in the opinion of the investigator, might compromise participant safety or interfere with the evaluation of the safety of the drug

Sites / Locations

  • Gabrail Cancer Center
  • MD Anderson Cancer CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment of NSCLC patients with EGFR or HER2 genetic alterations

Arm Description

Outcomes

Primary Outcome Measures

22-30 participants with treatment-related adverse events as assessed based on CTCAE v5.0.
Adverse events (AE), serious adverse events (SAE) and adverse events of special interest (AESI) will be assessed by Common Terminology Criteria for Adverse Events (CTCAE 5.0) grading system, changing from baseline and each treatment cycle (1 cycle=3 weeks). An Adverse Event (AE) is defined as any untoward medical occurrence in a participant who has enrolled in a study; it does not necessarily have a causal relationship with this treatment.

Secondary Outcome Measures

Cmax: Maximum Observed Plasma Concentration for FWD1509 MsOH
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for FWD1509 MsOH
T1/2: Terminal Half-life for FWD1509 MsOH
Terminal plasma half-life is the time required to divide the plasma concentration by two after reaching pseudo-equilibrium, and not the time required to eliminate half the administered dose.
AUC0-inf: Area Under the Plasma Concentration-time Curve From Time 0 to infinite time for FWD1509 MsOH
AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for FWD1509 MsOH
AUC0-24: Area Under the Plasma Concentration versus Time Curve From Time 0 to Time 24h for FWD1509
AUCss: Area Under the Plasma Concentration versus Time Curve From Time 0 to the End of the Dosing Interval
Apparent Plasma Clearance (CL/F), Apparent Volume of Distribution and Mean Residence Time (MRT)
Extent of Accumulation on Multiple Dosing (Rac)
ORR: Objective Response Rate
Confirmed ORR is defined as the proportion of participants who are confirmed to have achieved complete response (CR) or partial response (PR).
DoR: Duration of Response
Duration of response is defined as the time interval from the time that the measurement criteria are first met for CR/PR (whichever is first recorded) until the first date that PD is objectively documented.
DCR: Disease Control Rate
DCR is defined as the percentage of participants who have achieved CR, PR, or stable disease (SD) (in the case of SD, measurements must have met the SD criteria at least once after study entry at a minimum interval of 6 weeks) after the initiation of study drug.
PFS: Progression Free Survival
PFS is defined as the time interval from the date of randomization until the first date at which the criteria for progressive disease (PD) according to RECIST version 1.1 are met or death, whichever occurs first.
OS: Overall Survival
OS is defined as the interval from the date of randomization until death.

Full Information

First Posted
September 14, 2021
Last Updated
July 20, 2022
Sponsor
Forward Pharmaceuticals Co., Ltd.
Collaborators
WuXi Clinical
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1. Study Identification

Unique Protocol Identification Number
NCT05068024
Brief Title
A Study of FWD1509 in Adults With Non-Small Cell Lung Cancer
Acronym
FWD1509
Official Title
A Phase 1/2, Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Anti-Tumor Activity of FWD1509 MsOH in Advanced Non-Small Cell Lung Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
July 2022
Overall Recruitment Status
Recruiting
Study Start Date
August 23, 2021 (Actual)
Primary Completion Date
October 30, 2022 (Anticipated)
Study Completion Date
December 30, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Forward Pharmaceuticals Co., Ltd.
Collaborators
WuXi Clinical

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of this study is to characterize the safety and tolerability of FWD1509 MsOH in advanced NSCLC patients and establish the maximum tolerable dose (MTD), recommended phase 2 dose (RP2D) in advanced NSCLC patients.
Detailed Description
This study will be a first-in-human study evaluating the safety and tolerability of FWD1509 MsOH in subjects with advanced NSCLC, when FWD1509 MsOH is administered once daily as a single agent. FWD1509 MsOH is an oral TKI (Tyrosine Kinase Inhibitor) that blocks the function of tyrosine kinase. TKIs such as gefitinib, erlotinib or afatinib are recommended as the first-line therapy for EGFR mutated (exon 19 deletions or L858R point mutations in exon 21) NSCLC patients. However, the majority (>50%) of patients will develop acquired resistance after initially responding to gefitinib or erlotinib due to the occurrence of secondary mutations (mostly T709M) in EGFR. Osimertinib was subsequently developed to such secondary mutations, but for EGFRex20ins mutations, on which there is still no effective therapies focusing. FWD1509 MsOH is new generation EGFR-TKI targeting EGFR mutations such as exon 19 deletion, L858R substitution as well as T790M mutations. In particular, FWD1509 MsOH targets the EGFRex20ins mutation in NSCLC. In addition to activity against EGFR mutations, FWD1509 MsOH is also active against a variety of HER2 mutations. The development of FWD1509 MsOH at this stage is mainly focused on treatment of NSCLC tumors with EGFRex20ins mutations, followed by further exploration against other targets.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Carcinoma, Non-Small-Cell Lung
Keywords
FWD1509 MsOH in advanced non-small cell lung cancer, Forward Pharma, Forward, FWD1509, NSCLC, MsOH, FWD-001, First-in-human, Non-small cell lung cancer, Advanced solid malignancies, Solid malignancies, Solid tumor, EGFR, EGFR ex20ins, EGFR mutation, TKI, HER2

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Treatment of NSCLC patients with EGFR or HER2 genetic alterations
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
FWD1509 MsOH
Intervention Description
FWD1509 MsOH is administered orally once daily. The starting dose is 10 mg/day for dose-escalation phase, and the dose level to be investigated in the expansion study will depend on the emerging data. For dose-extension phase, the recommended Phase 2 dose will be administered.
Primary Outcome Measure Information:
Title
22-30 participants with treatment-related adverse events as assessed based on CTCAE v5.0.
Description
Adverse events (AE), serious adverse events (SAE) and adverse events of special interest (AESI) will be assessed by Common Terminology Criteria for Adverse Events (CTCAE 5.0) grading system, changing from baseline and each treatment cycle (1 cycle=3 weeks). An Adverse Event (AE) is defined as any untoward medical occurrence in a participant who has enrolled in a study; it does not necessarily have a causal relationship with this treatment.
Time Frame
18 months
Secondary Outcome Measure Information:
Title
Cmax: Maximum Observed Plasma Concentration for FWD1509 MsOH
Time Frame
Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose
Title
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for FWD1509 MsOH
Time Frame
Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose
Title
T1/2: Terminal Half-life for FWD1509 MsOH
Description
Terminal plasma half-life is the time required to divide the plasma concentration by two after reaching pseudo-equilibrium, and not the time required to eliminate half the administered dose.
Time Frame
Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose
Title
AUC0-inf: Area Under the Plasma Concentration-time Curve From Time 0 to infinite time for FWD1509 MsOH
Time Frame
Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose
Title
AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for FWD1509 MsOH
Time Frame
Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose
Title
AUC0-24: Area Under the Plasma Concentration versus Time Curve From Time 0 to Time 24h for FWD1509
Time Frame
Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose
Title
AUCss: Area Under the Plasma Concentration versus Time Curve From Time 0 to the End of the Dosing Interval
Time Frame
Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose
Title
Apparent Plasma Clearance (CL/F), Apparent Volume of Distribution and Mean Residence Time (MRT)
Time Frame
Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose
Title
Extent of Accumulation on Multiple Dosing (Rac)
Time Frame
Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose
Title
ORR: Objective Response Rate
Description
Confirmed ORR is defined as the proportion of participants who are confirmed to have achieved complete response (CR) or partial response (PR).
Time Frame
18 months
Title
DoR: Duration of Response
Description
Duration of response is defined as the time interval from the time that the measurement criteria are first met for CR/PR (whichever is first recorded) until the first date that PD is objectively documented.
Time Frame
18 months
Title
DCR: Disease Control Rate
Description
DCR is defined as the percentage of participants who have achieved CR, PR, or stable disease (SD) (in the case of SD, measurements must have met the SD criteria at least once after study entry at a minimum interval of 6 weeks) after the initiation of study drug.
Time Frame
18 months
Title
PFS: Progression Free Survival
Description
PFS is defined as the time interval from the date of randomization until the first date at which the criteria for progressive disease (PD) according to RECIST version 1.1 are met or death, whichever occurs first.
Time Frame
18 months
Title
OS: Overall Survival
Description
OS is defined as the interval from the date of randomization until death.
Time Frame
18 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria: Study-Wide Eligibility (Across All Study Parts): A subject will be eligible for inclusion in this study only if all of the following criteria apply. Have histologically or cytologically confirmed locally advanced or metastatic NSCLC (Stage IIIB/IIIC or IV) [JACC edition 8], and inclusion of Stage IIIB only if not a candidate for curative therapy Must have sufficient tumor tissue (either archived sample or recent biopsy) available for analysis: Phase 1 Dose-escalation part: EGFR and HER2 mutations (including but not limited toL858R, exon 19 deletion, T790M, ex20ins, 21exon, G719X, S768I, L861Q, etc. for EGFR and A775YVMG, C776insVC, P780ins GSP etc. for HER2) should be confirmed by previously documented evidence or central lab Patients with both EGFR and HER2 mutations may be included in the dose escalation phase Phase 1 Dose-expansion part and Phase 2: Have an EGFR in-frame exon 20 insertion test by any central lab Must have at least one measurable lesion as defined by response evaluation criteria in solid tumors (RECIST v1.1) Prior anti-cancer therapies: Previously treated with one or more regimens of systemic therapy for locally advanced or metastatic disease Disease progressed or intolerant to at least one line of systematic therapies including but not limited to any EGFR-target therapies or immunotherapies, for metastatic / local relapsed settings Male or female adult participants (aged 18 years or older, or as defined per local regulations) Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1 Minimum life expectancy of 3 months or more Adequate organ function at baseline Bone marrow function Absolute neutrophil count (ANC)≥1.5 x 10^9/L Platelets ≥100 x 10^9/L Hemoglobin ≥9 g/dL, criteria must be met without a transfusion within 2 weeks of the blood draw Hepatic function AST and ALT ≤3 x upper limit of normal (ULN); if liver metastases, then ≤ 5 x ULN Bilirubin ≤1.5 x ULN or ≤3 x ULN in the presence of documented Gilbert's Syndrome Renal function Creatinine clearance ≥50 ml/min (calculated by Cockcroft and Gault equation (Cockcroft DW, 1976) (Appendix 3) Willingness and ability to comply with scheduled visits and study procedures Exclusion Criteria: A subject will be not eligible for inclusion in this study if any of the following criteria apply: Received anticancer therapy including cytotoxic chemotherapy, biological products and investigational agents, ≤ 21 days prior to first dose of FWD1509 MsOH; or received prior EGFR TKIs (e.g., gefitinib, erlotinib or osimertinib) ≤7 days prior to the first dose FWD1509 MsOH Have been diagnosed with another primary malignancy other than NSCLC except for patients with adequately treated non-melanoma skin cancer, cervical cancer in situ or definitively treated non-metastatic prostate cancer, or participants with another primary malignancy who are definitively relapse-free with at least 3 years elapsed since the diagnosis of the other primary malignancy Received radiotherapy ≤14 days prior to the first dose of FWD1509 MsOH or have not recovered from radiotherapy-related toxicities; palliative radiation administered outside the chest and brain, stereotactic radiosurgery (SRS), and stereotactic body radiotherapy are allowed up to 7 days prior to the first dose of FWD1509 MsOH Received strong CYP3A inhibitors and inducers within 2 weeks prior to the first dose of FWD1509 MsOH; they should be discontinued at least 2 weeks prior to the first dose of FWD1509 MsOH and avoided throughout the study duration (see Appendix 6) Received concomitant medications (e.g., statins) which are substrates of BCRP, p-glycoprotein or OATP1B1/1B3 (dose escalation part of phase 1 study) Have undergone major surgery within 28 days prior to first dose of FWD1509 MsOH. Minor surgical procedures, such as catheter placement or minimally invasive biopsy, are allowed Brain Metastasis: Have known active brain metastases (have either previously untreated intracranial CNS metastases or previously treated intracranial CNS metastases with radiologically documented new or progressing CNS lesions), except for the following conditions Brain metastases are allowed if they have been treated with surgery and/or radiation and have been stable without requiring corticosteroids to control symptoms within 7 days before the first dose of FWD1509 MsOH and have no evidence of new or enlarging brain metastases Requiring corticosteroids to control symptoms within 7 days prior to the first dose of FWD1509 MsOH or during study period; patients previously treated for CNS metastases who are clinically stable, have no new lesions, and who do not need treatment with a corticosteroid within the 7 days before the first dose of FWD1509 MsOH and during study period are allowed to be enrolled Have current spinal cord compression (symptomatic or asymptomatic and detected by radiographic imaging) or leptomeningeal disease (symptomatic or asymptomatic) Have significant, uncontrolled, or active cardiovascular disease QCc-related criteria: A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval >480 milliseconds (ms) (CTCAE grade 1) using Fredericia's QT correction formula A history of additional risk factors for Torsades de Pointes (TdP) (e.g., heart failure, hypokalemia, family history of Long QT Syndrome Have significant, uncontrolled, or active renal disease Have a known history of uncontrolled hypertension (per institution practice); participants with hypertension should be under treatment on study entry to control blood pressure Have any abnormal changes in the cornea or retina that may increase the risk of ocular toxicity during screening Have an ongoing or active infection, including but not limited to, the requirement for intravenous (IV) antibiotics, or a known history of human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV). Testing is not required in the absence of history Currently have or have a history of interstitial lung disease, radiation pneumonitis that required steroid treatment, or drug-related pneumonitis Female participants who are lactating and breastfeeding or have a positive urine or serum pregnancy test during the screening period Have gastrointestinal illness or disorder that could affect oral absorption of FWD1509 MsOH Have any condition or illness that, in the opinion of the investigator, might compromise participant safety or interfere with the evaluation of the safety of the drug
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jo-Han Wang, Project Manager
Phone
+1-647-649-2850
Email
jo-han.wang@wuxiapptec.com
First Name & Middle Initial & Last Name or Official Title & Degree
Ling Zeng
Phone
+86 15010623457
Email
zengl@forward-pharm.com
Facility Information:
Facility Name
Gabrail Cancer Center
City
Canton
State/Province
Ohio
ZIP/Postal Code
44718
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Brittany Dessecker
Phone
330-492-3345
Ext
X213
Email
bdessecker@gabrailcancercenter.com
Facility Name
MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Terri Alexander, SN
Phone
346-234-9744
Email
TLAlexander@mdanderson.org

12. IPD Sharing Statement

Learn more about this trial

A Study of FWD1509 in Adults With Non-Small Cell Lung Cancer

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