Study of M7824 and Paclitaxel Combination as a Second-line Treatment in Patients With Recurrent/Metastatic Gastric Cancer

An Open Label, Single-arm, Multi-center Phase 1b/2 Combination Study of M7824 (Bintrafusp Alfa) and Paclitaxel in Recurrent/Metastatic Gastric Cancer as a Second-line Treatment

This is a Phase 1b/2 study to identify the recommended dose of M7824 for further study with weekly paclitaxel, and to assess the safety and clinical efficacy of this combined treatment in advanced gastric cancer after first line treatment. The study will be conducted in two parts: Part 1 (Phase 1b) dose escalation study to determine the MTD and RP2D of weekly paclitaxel in combination with fixed dose M7824, Part 2 (Phase 2) to further evaluate the safety and tolerability of the combination of M7824 and paclitaxel at the RP2D and determine anti-tumor activity.

Study Overview

• Status: Completed
• Conditions: Recurrent/Metastatic Gastric Cancer
• Intervention / Treatment: Drug: M7824+paclitaxel

• Study Type: Interventional
• Enrollment (Actual): 49
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Yonsei University Health System, Severance Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Able and willing to give written informed consent and has signed the informed consent form (ICF), prior to performance of any trial activities.
2. Eligible male and female subjects aged ≥19 years.
3. Histologically or cytologically proven metastatic or locally advanced HER2 negative gastric cancer after 1st line failure.
4. ECOG performance status of 0 to 1 at trial entry.
5. Life expectancy ≥12 weeks as judged by the Investigator.
6. Adequate hematological function defined by white blood cell (WBC) count ≥3×109/L with absolute neutrophil count (ANC) ≥1.5×109/L, lymphocyte count ≥0.5×109/L, platelet count ≥100×109/L, and Hb ≥9 g/dL (in absence of blood transfusion).
7. Adequate hepatic function defined by a total bilirubin level ≤1.5×ULN, an AST level ≤1.5×ULN, and an ALT level ≤1.5×ULN. For subjects with liver involvement in their tumor, AST ≤5.0×ULN, ALT ≤5.0×ULN, and bilirubin ≤3.0 is acceptable.
8. Adequate renal function defined by an estimated creatinine clearance >50 mL/min according to the Cockcroft-Gault formula or by measure of creatinine clearance from 24-hour urine collection.
9. Adequate coagulation function: normal international normalized ratio (INR), PT ≤1.5×ULN and activated partial thromboplastin time (aPTT) ≤1.5×ULN.
10. HIV patient must be stable on ART for at least 4 weeks, having documented evidence of multi-drug resistance, viral load of <400 copies/ml and CD4+ T-cells ≤350 cells/µL.
11. HBV/HCV positive participant must be on a stable dose of antiviral therapy, having HBV viral load below the limit of quantification (HBV titer <2000 IU/ml) and HCV RNA is not detected.
12. Has measurable or evaluable disease as determined by RECIST 1.1.

Exclusion Criteria:

1. Concurrent treatment with non-permitted drugs.
2. Prior therapy with any antibody/drug targeting T cell coregulatory proteins (immune checkpoints) such as anti-PD-1, anti-cytotoxic T lymphocyte antigen-4 (CTLA-4) antibody, or anti-4-1BB antibody, is not allowed.
3. Prior therapy with any antibody/drug targeting TGFβ or TGF receptor.
4. Anticancer treatment within 21 days before the start of trial treatment, e.g., cytoreductive therapy, radiotherapy (with the exception of palliative bone-directed radiotherapy), immune therapy, or cytokine therapy.
5. Major surgery within 28 days before the start of trial treatment (excluding prior diagnostic biopsy).
6. Systemic therapy with immunosuppressive agents within 7 days before the start of trial treatment; or use of any investigational drug within 28 days before the start of trial treatment.
7. Has persistent ≥Grade 2 toxicity that was not resolved from previous anticancer treatment, such as neuropathy (exceptions are alopecia and anemia).
8. A WOCBP who has a positive urine pregnancy test within 72 hours prior to allocation.
9. Has received a live vaccine within 30 days prior to the first dose of study drug.
10. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
11. Has a known additional malignancy that is progressing or has required active treatment within the past 5 years.
12. Has known active CNS metastases and/or carcinomatous meningitis.
13. Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids, or immunosuppressive drugs).
14. Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
15. Has an active infection requiring systemic therapy.
16. Has uncontrolled or severe cardiovascular disease, as per following criteria: Myocardial infarction within 180 days before the start of trial treatment; Uncontrolled angina pectoris within 180 days before the start of trial treatment; New York Heart Association (NYHA) Class III or IV congestive heart failure; Uncontrolled hypertension despite appropriate treatment (systolic blood pressure ≥150 mmHg or diastolic blood pressure ≥90 mmHg lasting 24 hours or more); Arrhythmia requiring treatment
17. History of bleeding diathesis or recent major bleeding event.
18. Has a known history of Human Immunodeficiency Virus (HIV) without treatment.
19. Has an active of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive and HBV titer >2000 IU/ml) or known active Hepatitis C virus (defined as HCV RNA is detected) infection.
20. Has an active TB (Bacillus Tuberculosis) with treatment.
21. Has known history of hypersensitivity to one or more of the study treatments or their substances, or known severe hypersensitivity to monoclonal antibodies (≥Grade 3), history of anaphylaxis, or uncontrolled asthma within 5 months before start of trial treatment.
22. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
23. Have received more than 2nd line of chemotherapy.
24. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
25. Otherwise inappropriate for this study in the investigator's or sub-investigator's opinion.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Study treatment	Drug: M7824+paclitaxel; M7824 will be administered intravenously at a dose of 1200 mg every 3 weeks in combination with paclitaxel 80 (or 70) mg/m2 once a week for 3 weeks (each cycle is 4 weeks)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Phase 1b: Dose-limiting toxicity in subjects with M7824 and paclitaxel combination treatment	Within first 4 weeks
Phase 2: Progression-free survival in subjects with M7824 and paclitaxel combination treatment	At 24 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall survival	3 months after the last dose study treatment of the last subject
Objective response rate according to RECIST 1.1	3 months after the last dose study treatment of the last subject
Disease control rate according to RECIST 1.1	3 months after the last dose study treatment of the last subject
Duration of response according to RECIST 1.1	3 months after the last dose study treatment of the last subject
Progression-free survival according to RECIST 1.1	3 months after the last dose study treatment of the last subject
Safety and Tolerability, in terms of the number, severity, and duration of treatment-emergent adverse events as assessed by CTCAE v5.0	Throughout the overall trial period as well as up to 3 months after the last dose study treatment for each subject

Collaborators and Investigators

• Sponsor: Yonsei University
• Investigators: Principal Investigator: Sun Young RHA, MD, PhD, Yonsei Cancer Center, Severance Hospital, Yonsei University College of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): June 2, 2021
• Primary Completion (Actual): October 27, 2023
• Study Completion (Actual): October 27, 2023

Study Registration Dates

• First Submitted: April 1, 2021
• First Submitted That Met QC Criteria: April 5, 2021
• First Posted (Actual): April 8, 2021

Study Record Updates

• Last Update Posted (Actual): May 6, 2024
• Last Update Submitted That Met QC Criteria: May 2, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms; Neoplasms by Site; Disease Attributes; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms; Recurrence; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Paclitaxel
• Other Study ID Numbers: 4-2020-1334

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No