Study to Evaluate Efficacy of PDR001 in Patients With Squamous Cell Carcinoma of the Esophagus

NCT03785496 | Unknown Phase 2

• 1 other identifier: 4-2018-0938
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

Brief Summary

Single arm phase II PDR001( 300mg, IV) will be treated every 3 weeks

Conditions

Histologically Confirmed Unresectable or Metastatic Squamous Cell Carcinoma of the Esophagus Who Failed on Standard Treatment

Outcome Measures

Primary Outcomes (1)

• To evaluate efficacy of PDR001 by Objective Response rate by RECIST(Response Evaluation Criteria In Solid Tumors)

  In the first stage of the trial, 22 patients will be recruited, and their tumor response will be assessed RECIST criteria, which is widely used tumor assessment criteria in immuno-oncology agent trials. The best response until 6 months according to irRECIST will be evaluated, and this trial will proceed to second stage if three or more respondents (irPR or irCR) are observed among 22 patients. The response (PR or CR) should be confirmed by next disease assessment(6 weeks/2cycles after initial response). Subjects who discontinue trial treatment for a reason other than recurrence will move into the Follow-Up Phase and should be assessed every 16 weeks (± 14 days) by radiologic imaging to monitor disease status.

  Repeated tumor imaging will be performed every 2 cycle (each cycle is 21 days) after baseline imaging

Secondary Outcomes (3)

• To evaluate antitumor efficacy of PDR001: PFS(Progression-Free Survival)

  Biopsies will be taken during the screening period (e.g., within 7 days before treatment [pre-dose]), on treatment (Day 22 of first dose) and post-treatment (e.g., within 28 days after progression)

• To evaluate antitumor efficacy of PDR001: OS(Overall survival)

  Biopsies will be taken during the screening period (e.g., within 7 days before treatment [pre-dose]), on treatment (Day 22 of first dose) and post-treatment (e.g., within 28 days after progression)

• To evaluate antitumor efficacy of PDR001

  Biopsies will be taken during the screening period (e.g., within 7 days before treatment [pre-dose]), on treatment (Day 22 of first dose) and post-treatment (e.g., within 28 days after progression)

Study Arms (1)

PDR001

EXPERIMENTAL

PDR001 will be administered once every 3 weeks via i.v. infusions over 30 minutes, respectively. Infusions of each antibody can be extended to up to 2 hours if clinically indicated. A scheduled dose of ongoing study drugs may be delayed by up to 7 days to recover from previous AEs or a missed visit. If a scheduled dose of ongoing study drugs is delayed longer than 7 days due to an unresolved AE, the administration should be skipped and treatment resumed at the next scheduled dose. The assessment schedule will be shifted accordingly.

Drug: PDR001

Interventions

PDR001 DRUG

PDR001 will be administered once every 3 weeks via i.v. infusions over 30 minutes, respectively. Infusions of each antibody can be extended to up to 2 hours if clinically indicated. A scheduled dose of ongoing study drugs may be delayed by up to 7 days to recover from previous AEs or a missed visit. If a scheduled dose of ongoing study drugs is delayed longer than 7 days due to an unresolved AE, the administration should be skipped and treatment resumed at the next scheduled dose. The assessment schedule will be shifted accordingly.

PDR001

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed squamous cell carcinoma of the esophagus
• Age ≥ 20
• ECOG PS 0-2
• Ineligibility for local therapy (surgery or radiotherapy), including but not limited to:
• Patients with distant metastases (stage M1, stage IVB)
• Patients with disease progression and/or recurrence after chemoradiotherapy
• Patients with disease recurrence after surgical excision for primary esophageal cancer
• Ineligible patient for surgery and/or CCRT due to medical condition
• Ineligible patients with T4b for surgery and/or CCRT due to invasive organs such as large vessels, heart
• Prior palliative chemotherapy including platinum-based chemotherapy. When recurred within 6 months of definitive/neoadjuvant/adjuvant chemo-, the chemotherapy is considered a line of therapy
• At least one uni-dimensionally measurable disease as defined by RECIST ver 1.1
• Adequate organ function for treatment (Table 1)
• Lead electrocardiogram (ECG) with normal tracing or non-clinically significant changes that do not require medical intervention
• QTcF interval ≤470 msec and without history of Torsades de Pointes or other symptomatic QTcF abnormality
• LVEF (by MUGA or echocardiogram) of ≥50%

You may not qualify if:

• Presence of symptomatic CNS metastases, or CNS metastases that require local CNS-directed therapy (such as radiotherapy or surgery). Patients with treated brain metastases should be neurologically stable (for 4 weeks post treatment and prior to study enrollment) and off of steroids for at least 2 weeks before administration of any study drug.
• Previous treatment with anti- PD-1, and/or PD-L1
• Two or more previous systemic cytotoxic chemotherapy (chemotherapy administered with concurrent radiotherapy for local control is not counted)
• Any major operation within 4 weeks of baseline disease assessment
• Any medical condition that would, in the investigator's judgement, prevent the patient's participation in the clinical study due to safety concerns, compliance with clinical study procedures or interpretation of study results, including but not limited to:
• Prior immune-related adverse events requiring treatment discontinuation
• Ongoing symptomatic interstitial lung disease (ILD), noninfectious pneumonitis or history of drug induced interstitial lung disease
• Impaired cardiac function or clinically significant cardiac disease, including any of the following:
• Clinically significant and/or uncontrolled heart disease such as congestive heart failure requiring treatment (NYHA Grade ≥ 2), uncontrolled hypertension or clinically significant arrhythmia
• QTcF \> 470 msec on screening ECG or congenital long QT syndrome
• Acute myocardial infarction or unstable angina pectoris \< 3 months prior to study entry
• Active infection, including active tuberculosis requiring systemic antibiotic therapy
• Known human immunodeficiency virus (HIV) infection (no testing required).
• Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, or HBV/HCV carriers/infections requiring antiviral treatment (testing required)
• Use of any live vaccines against infectious diseases (e.g. varicella, pneumococcus) within 4 weeks of initiation of study treatment.

Sponsors & Collaborators

• Yonsei University: lead

Study Sites (1)

Yonsei University Health System, Severance Hospital

Seoul, South Korea

Location

Related Publications (1)

• Lee DK, Park SR, Kim YH, Lee YG, Shin SJ, Ahn BC, Lee SS, Lim SM, Kim HR, Cho BC, Hong MH. A phase 2 study of spartalizumab (PDR001) among patients with recurrent or metastatic esophageal squamous cell carcinoma (KCSG HN18-17, K-MASTER project 12). Oncoimmunology. 2024 Jun 24;13(1):2371563. doi: 10.1080/2162402X.2024.2371563. eCollection 2024.

  PMID: 38919826 DERIVED

MeSH Terms

Interventions

spartalizumab

Study Officials

• Byoung Chul Cho

  Severance Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 6, 2018
• First Posted: December 24, 2018
• Study Start: February 18, 2020
• Primary Completion: January 1, 2022
• Study Completion: January 1, 2024
• Last Updated: May 6, 2021

Record last verified: 2021-05

Locations

KR (1)