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

NCT04835896 | Completed Phase 1 DMC

• 1 other identifier: 4-2020-1334
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Recurrent/Metastatic Gastric Cancer

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (6)

• 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

Study Arms (1)

Study treatment

EXPERIMENTAL

Drug: M7824+paclitaxel

Interventions

M7824+paclitaxel DRUG

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)

Study treatment

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able and willing to give written informed consent and has signed the informed consent form (ICF), prior to performance of any trial activities.
• Eligible male and female subjects aged ≥19 years.
• Histologically or cytologically proven metastatic or locally advanced HER2 negative gastric cancer after 1st line failure.
• ECOG performance status of 0 to 1 at trial entry.
• Life expectancy ≥12 weeks as judged by the Investigator.
• 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).
• 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.
• 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.
• Adequate coagulation function: normal international normalized ratio (INR), PT ≤1.5×ULN and activated partial thromboplastin time (aPTT) ≤1.5×ULN.
• 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.
• 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.
• Has measurable or evaluable disease as determined by RECIST 1.1.

You may not qualify if:

• Concurrent treatment with non-permitted drugs.
• 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.
• Prior therapy with any antibody/drug targeting TGFβ or TGF receptor.
• 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.
• Major surgery within 28 days before the start of trial treatment (excluding prior diagnostic biopsy).
• 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.
• Has persistent ≥Grade 2 toxicity that was not resolved from previous anticancer treatment, such as neuropathy (exceptions are alopecia and anemia).
• A WOCBP who has a positive urine pregnancy test within 72 hours prior to allocation.
• Has received a live vaccine within 30 days prior to the first dose of study drug.
• 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.
• Has a known additional malignancy that is progressing or has required active treatment within the past 5 years.
• Has known active CNS metastases and/or carcinomatous meningitis.
• 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).
• Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
• Has an active infection requiring systemic therapy.

Sponsors & Collaborators

• Yonsei University: lead

Study Sites (1)

Yonsei University Health System, Severance Hospital

Seoul, South Korea

Location

MeSH Terms

Conditions

Stomach Neoplasms

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Study Officials

• Sun Young RHA, MD, PhD

  Yonsei Cancer Center, Severance Hospital, Yonsei University College of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 1, 2021
• First Posted: April 8, 2021
• Study Start: June 2, 2021
• Primary Completion: October 27, 2023
• Study Completion: October 27, 2023
• Last Updated: May 6, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)