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Phase 1 Study of FS-1502 in Patients With HER2 Expressed Advanced Solid Tumors and Local Advanced or Metastatic, HER2 Positive Breast Cancer.

  • Clinicaltrials.gov identifier

    NCT03944499

  • Recruitment Status

    Not yet recruiting

  • First Posted

    May 9, 2019

  • Last update posted

    May 13, 2019

Study Description

Brief summary:

This study is being done for the following reasons: - The study has two parts. The purpose of the first part (Phase 1a) of the study is to find out the highest dose of FS-1502 (Trastuzumab Monomethyl Auristatin F), an Anti-HER2 Antibody Drug Conjugate (ADC) that can be given safely. - The purpose of the second part of the study (Phase 1b) is to observe the treatment effect of Recommended Phase 2 Dose (RP2D) of FS-1502 in patients with HER2+ breast cancer who are relapsed or refractory to the previous anti-HER2 therapy.

  • Condition or Disease:Solid Tumor
    Breast Cancer
  • Intervention/Treatment: Drug: FS-1502
  • Phase: Phase 1

Detailed Description

The study is designed as an open label, single arm, Phase 1a/1b study with a dose-escalation phase to evaluate FS-1502 in patients with HER2 expressed advanced malignant solid tumors (phase 1a) and an expanded cohort (phase 1b) to evaluate FS-1502 in patients with metastatic, HER2-positive breast cancer. The primary aim of the phase 1a portion of this study is to determine the safety and tolerability of FS-1502. The primary aim of the phase 1b portion is to demonstrate efficacy.

Study Design

  • Study Type: Interventional
  • Estimated Enrollment: 92 participants
  • Intervention Model: Single Group Assignment
  • Masking: None (Open Label) ()
  • Primary Purpose: Treatment
  • Official Title: A Phase 1, Multicenter, Open-label, Single-arm Study: A Dose-escalation Phase (Phase 1a) Evaluating FS-1502 in Patients With HER2 Expressed Advanced Solid Tumors; and a Dose-expanded Cohort (Phase 1b) Evaluating FS-1502 in Patients With Local Advanced or Metastatic, HER2 Positive Breast Cancer.
  • Estimated Study Start Date: May 2019
  • Estimated Primary Completion Date: January 2025
  • Estimated Study Completion Date: June 2025

Arms and interventions

Arm Intervention/treatment
Experimental: FS-1502
Drug: FS-1502
Drug: FS-1502 Dose-Escalation Phase (Phase 1a) - FS-1502 Dose-escalation will be proceeded on standard 3+3 design with starting dose of 0.1 mg/kg, IV, once per 28 days, 28 days as a cycle. Dose level 1: 0.1 mg/kg; Dose level 2: 0.2 mg/kg; Dose level 3: 0.4 mg/kg; Dose level 4: 0.6 mg/kg; Dose level 5: 0.8 mg/kg; Dose level 6: 1.0 mg/kg; Dose level 7: 1.3 mg/kg. Dose-expansion Phase (Phase 1b) -RP2D determined in phase 1a, IV, once per 28 days, 28 days as a cycle.

Outcome Measures

  • Primary Outcome Measures: 1. Dose limiting toxicity (DLT) within 28 days of first single dose of FS-1502. [ Time Frame: At the end of Cycle 1 (each cycle is 28 days). ]
    To evaluate dose limiting toxicity (DLT) within 28 days from first dose according to DLT criteria per protocol
  • 2. Overall response rate (ORR) by measurement of target lesions [ Time Frame: Approximately 2 years. ]
    Assess ORR per 2 cycles according to RECIST 1.1 criteria
  • Secondary Outcome Measures: 1. Incidence Rate and type of treatment emergent adverse event (Safety) [ Time Frame: Approximately 3 years. ]
    Evaluate according to CTCAE version 5.0.
  • 2. Number of Participants with serious adverse events and adverse reactions that leading to treatment permanent discontinuation of FS1502. [ Time Frame: Approximately 2 years. ]
  • 3. Incidence of deaths and causes within 30 days after the last dose. [ Time Frame: Approximately 3 years. ]
  • 4. Progression free survival (PFS) [ Time Frame: Approximately 2 years. ]
  • 5. Overall survival (OS) [ Time Frame: Approximately 3 years. ]
  • 6. 1-year overall survival (OS) rate [ Time Frame: 1 years ]
  • 7. Duration of response (DoR) [ Time Frame: 2 years ]
    Length of time response continued
  • 8. Clinical benefit response (CBR) [ Time Frame: 2 years ]
    Percentage of participants achieve clinical benefit (complete response (CR), partial response (PR) or stable disease (SD) more than 6 months) from the treatment.
  • 9. Area under the plasma concentration versus time curve (AUC) [ Time Frame: Approximately 2 years. ]
    Measure the AUC of FS-1502 and it metabolites (MMAF).
  • 10. Peak Plasma Concentration (Cmax) [ Time Frame: Approximately 2 years. ]
    Measure the Cmax of FS-1502 and it metabolites (MMAF).
  • 11. Time to maximum concentration (tmax) [ Time Frame: Approximately 2 years. ]
    Measure the tmax of FS-1502 and it metabolites (MMAF).
  • 12. Elimination half life (T1/2) [ Time Frame: Approximately 2 years. ]
    Measure the T1/2 of FS-1502 and it metabolites (MMAF).
  • 13. Clearance (Cl) [ Time Frame: Approximately 2 years. ]
    Measure the Clearance of FS-1502 and it metabolites (MMAF).
  • 14. Anti-FS-1502 antibody [ Time Frame: Approximately 2 years. ]
    Measure the anti-FS-1502 antibody to demonstrade the immunogenicity of FS-1502.

Eligibility Criteria

  • Ages Eligible for Study: 18 to 70 Years (Adult, Older Adult)
  • Sexes Eligible for Study: All
  • Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Age ≥18 years and ≤ 70 years at the time of study registration (men and women
eligible);

2. Phase Ia dose-escalation study:

Patients with HER2 expressed advanced malignant solid tumor had failed to standard
therapy (including surgery, chemotherapy, radiation therapy or biotherapy), or no
standard therapy is available.

1. HER2 overexpression: IHC3+, IHC2+/FISH+, or FISH+

2. HER2 low expression: IHC1+, IHC2+/FISH-

Phase Ib dose-expanded study:

Histologically or cytologically confirmed breast cancer patients who have failed to
prior trastuzumab treatment. Including patients with locally advanced or metastatic
breast cancer and those who have relapsed after standard adjuvant chemotherapy
(treatment for more than 3 months). Details as follows:

1. HER2 positive (defined as IHC3+ or IHC2+/FISH+);

2. At least one standard trastuzumab treatment or other biosimilar has been received
and the treatment failed.

3. Provide evidence of disease progression or intolerable toxicity as confirmed by
the investigator or medical history recorded prior to enrollment.

The enrollment can be based on written HER2 test report from certified local lab, but
sufficient paraffin sections or fresh tumor tissue specimens must be provided to the
central laboratory for confirmation.

3. The ECOG performance status must be 0 or 1.

4. Expected survival for at least 12 weeks.

5. Has adequate organ and bone marrow function: absolute neutrophil count (ANC) ≥
1.5x109/L; hemoglobin ≥ 90g/L (without red blood cell infusion within 14 days);
platelet count ≥ 100x109/L; Total bilirubin ≤ 1.5x upper limit normal (ULN), or ≤ 3x
ULN if with Gilbert syndrome; aspartate aminotransferase (AST) and alanine
aminotransferase (ALT) ≤ 2.5x ULN; AST and ALT ≤ 5x ULN if liver metastasis; Serum
creatinine 50%.

6. Has at least one measurable lesion by RECIST version 1.1.

7. Male or female patients with fertility must agree to use effective contraceptive
methods during the study period and within 30 days of the last dose of study therapy,
such as dual barrier contraceptive methods, condoms, oral or injectable
contraceptives, and intrauterine devices.

8. Ability to understand and voluntarily sign written informed consent.

Exclusion Criteria:

1. Patients who received chemotherapy, radiotherapy, major surgery or other anti-tumor
treatment within 4 weeks prior to the start of dosing.

2. Patients who have participated in other clinical trials 4 weeks before the start of
study drug administration or within 5 drug half-life periods; patients who have
received similar treatments.

3. Uncontrolled central nervous system metastasis or injury (Patients who have been
treated with gamma knife and have a stable disease for more than 3 months are allowed
to enroll).

4. Patients with uncontrolled diabetes mellitus (Patients who are receiving an insulin
regimen or a hypoglycemic regimen and are evaluated as having good glycemic control by
a specialist are allowed to enroll).

5. Has not recovered from previous anti-tumor treatment-related toxic reactions (>
NCI-CITCAE 5.0 Grade 2), except for hair loss. The neurotoxicity of patients who have
previously received chemotherapy needs to be restored to NCI-CTCAE 5.0 level 2 or
below.

6. Patients who have used potent CYP3A inhibitors within 14 days prior to the start of
dosing (Boprevir, cobaster, cognac, dannoprevir and ritonavir (j), ethiravir and
ritonavir (j), indinavir and ritonavir ( j), posaconazole and ritonavir (j), lopinavir
and ritonavir (j), saquinavir and ritonavir (j), telanavir and ritonavir (j), parylene
and ritonavir and (obivir and or dasab) (j), grapefruit, itraconazole, ketoconazole,
telaprevir, vinegar Orchard, voriconazole, clarithromycin, diltiazem, aldelis,
nefazodone, nelfinavir) or strong inducer (carbamazepine, enzalutamide, mitoxantrone,
phenytoin, rifampicin, St. John's wort, etc.); P-gp transporter inducer or inhibitor;
(j) indicates inhibition of CYP3A when in combination with ritonavir.

7. Patients who are taking medications that prolong the QTc interval (mainly Ia, Ic, and
III antiarrhythmic drugs) or patients with risk factors for QTc interval prolongation,
such as uncorrectable hypokalemia, hereditary long QT syndrome. Drugs that potentially
prolong the QTc interval can be found at
https://crediblemeds.org/index.php/tools/pdfdownload?f=cql_en

8. Cardiac function and disease meeting one of the following conditions:

1. Three 12-lead electrocardiogram (ECG) measurements at the research center during
the screening period. Calculate the average of three measurements based on the
QTc formula, QTc > 470 milliseconds.

2. New York Heart Association (NYHA) graded ≥3 congestive heart failure.

3. Clinically significant arrhythmias, including but not limited to complete left
bundle branch conduction abnormality, II degree atrioventricular block.

9. Pregnant or lactating woman.

10. Allergic to any excipients of FS-1502.

11. Clinically significant active bacterial, fungal or viral infections, including
hepatitis B (hepatitis B virus surface antigen positive and hepatitis B virus DNA over
1000 IU/ml) or hepatitis C (hepatitis C virus RNA positive), human immunodeficiency
virus infection ( HIV positive).

12. Any other disease or condition of clinical significance (eg, active or uncontrollable
infection, etc.) considered by investigator that may affect protocol compliance or
affect patient signature of ICF.

Contacts and Locations

Contacts

Contact: BINGHE XU, PhD 010-87788826 xubingheBM@163.com

Contact: QIAO LI, PhD 18500027849 Liqiaopumc@qq.com

Locations

Sponsors and Collaborators

Shanghai Fosun Pharmaceutical Development Co, Ltd.

Investigators

Principal Investigator: BINGHE XU, PhD National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College

More Information

  • Responsible Party: Shanghai Fosun Pharmaceutical Development Co, Ltd.
  • ClinicalTrials.gov Identifier: NCT03944499 History of Changes
  • Other Study ID Numbers: FS-CY1502-Ph1-01
  • First Posted: May 9, 2019 Key Record Dates
  • Last Update Posted: May 13, 2019
  • Last Verified: May 2019
  • Individual Participant
    Data (IPD) Sharing
    Statement:

  • Plan to Share IPD: No
  • Studies a U.S. FDA-regulated Drug Product: No
  • Studies a U.S. FDA-regulated Device Product: No
  • Additional relevant MeSH terms: Breast Neoplasms