PD-1 Inhibitor INCMGA00012 as Consolidation Therapy After Definitive Concurrent Chemoradiotherapy

NCT04494009 | Active Not Recruiting Phase 2

• 1 other identifier: MC20-01
• Study Type: interventional
• Target: 110
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a randomized, multi-center, open-label, phase II study of a PD-1 inhibitor (INCMGA00012) versus observation as consolidation therapy after definitive concurrent chemoradiotherapy in patients with locally advanced ESCC who have not progressed following definitive chemoradiotherapy.

Conditions

Esophageal Cancer

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival per RECIST 1.1

  Every 12 weeks during the first two years after randomization then every 24 weeks

  5 Years

Secondary Outcomes (7)

• Overall Survival

  5 Years

• Progression Free Survival per iRECIST

  5 Years

• Time To Progression per RECIST 1.1

  5 Years

• Time To Progression per iRECIST Time To Progression per iRECIST

  5 Years

• To compare pattern of first cause of progression

  5 Years

Study Arms (2)

INCMGA00012 군

EXPERIMENTAL

INCMGA00012 500 mg iv every 4 weeks for up to 12 months

Drug: INCMGA00012

Observation arm

NO INTERVENTION

followed up every 12 weeks for up to 12 months

Interventions

INCMGA00012 DRUG

INCMGA00012 (also known as MGA012) is a humanized, hinge-stabilized IgG4 monoclonal antibody against human PD-1, which blocks the interaction of PD-1 with PD-L1 and PD-L2, interrupting PD-1 signaling, enhances antigen-induced interferon-γ release, and has a favorable preclinical profile.

INCMGA00012 군

Eligibility Criteria

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

You may qualify if:

• Be willing and able to provide written informed consent for the trial.
• Be ≥19 years of age on the day of signing the informed consent.
• Have ECOG performance status 0-2 (Appendix 1).
• Have histologically proven esophageal squamous cell carcinoma (ESCC).
• Have demonstrated cT1b N1-3 M0 or T2-4b N0-3 M0 (8th AJCC staging system) before definitive chemoradiotherapy (Appendix 2).
• Have completed definitive concurrent chemoradiotherapy for esophageal cancer due to unresectable disease status (such as cervical esophageal cancer and T4b), medically inoperable status, or patient's refusal of undergoing surgery.
• Have received fluoropyrimidine or taxane plus platinum chemotherapy (including, but not limited to fluorouracil plus cisplatin, capecitabine plus cisplatin, and paclitaxel plus carboplatin according to the institute standard of care regimens) concurrent with radiation therapy. One or two cycles of induction chemotherapy before chemoradiotherapy is allowed, but chemotherapy after concurrent chemoradiotherapy is not allowed.
• Have received a total dose of radiation of at least 50 Gy as part of concurrent chemoradiotherapy.
• Have not progressed following definitive chemoradiotherapy assessed by 18F-FDG-PET (or PET-CT) scan, esophagogastroduodenoscopy (EGD), and chest CT. Clinical response should be evaluated within 4 to 8 weeks after completing definitive chemoradiotherapy, and within 3 weeks before randomization.
• Have available pre-treatment tumor tissue for biomarker analyses. Either 1 formalin-fixed paraffin embedded (FFPE) tumor tissue block or 20 unstained tumor tissue slides must be submitted for biomarker evaluation. Post-chemoradiation biopsy should be performed if it is technically feasible and is not associated with unacceptable clinical risk, and in case of pathologic residual cancer, tumor tissue for biomarker analyses should be submitted (Either 1 FFPE tumor tissue block or 20 unstained tumor tissue slides).
• Have adequate major organ functions as demonstrated by following laboratory results obtained within 14 days prior to randomization (these lab criteria should be also met within 7 days before initiation of study drug):
• Adequate bone marrow function as defined by absolute neutrophil count (ANC) ≥ 1,000/mm3 and platelet count ≥ 75,000/mm3 without receiving growth factors or blood transfusion within 7 days before the laboratory testing.
• Adequate renal function with serum creatinine ≤ 1.5 x upper limit of normal (ULN) or creatinine clearance ≥50 mL/minute by calculation using the Cockcroft-Gault formula (Appendix 3) or measurement using a preferred method per institute standard of care.
• Adequate hepatic function with alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x ULN, and serum total bilirubin ≤ 1.5 x ULN except for subjects with Gilbert syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology) who may be enrolled despite a total bilirubin level \> 1.5 x ULN.
• Female subjects of childbearing potential must have a negative urine or serum pregnancy test within 14 days prior to randomization. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.

You may not qualify if:

• Has demonstrated disease progression while or after completion of definitive chemoradiotherapy for locally advanced ESCC.
• Has received sequential chemotherapy or chemoradiotherapy after completion of concurrent chemoradiotherapy for locally advanced ESCC.
• Has received any immunotherapy or investigational drug within 4 weeks prior to randomization.
• Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
• Any concurrent chemotherapy, immunotherapy, biologic or hormonal therapy, investigational agent, or local treatment (except for stent insertion or feeding enterostomy for palliative intent) for cancer treatment.
• Any unresolved toxicities CTCAE grade ≥2 from prior therapy with the exception of alopecia, fatigue, and neuropathy.
• Has undergone major surgery within 4 weeks prior to entry into the study.
• Has an active autoimmune disease that has required systemic treatment within the 2 years prior to entry into the study (i.e., with use of disease-modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal insufficiency of pituitary insufficiency) is not considered a form of systemic treatment and is allowed.
• Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis)
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (\>10 mg/day prednisolone or equivalents) or any other form of immunosuppressive therapy within 14 days prior to entry into the study. Note: A use of topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption) is allowed. A brief course of corticosteroids for prophylaxis (e.g., contrast dye allergy) or for treatment of non-autoimmune conditions (e.g., delayed-type hypersensitivity reaction caused by contact allergen) is permitted.
• Has a history of organ transplant, including stem cell allograft.
• Has received a live vaccine within 30 days prior to entry into the study. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed.
• Has an active infection requiring systemic therapy.
• Has known history of Human Immunodeficiency Virus (HIV) infection.
• Has active HBV (detectable HBsAg or HBV DNA) or HCV infection (detectable HCV RNA):

Sponsors & Collaborators

• Asan Medical Center: lead

Study Sites (1)

Asan Medical Center

Seoul, 05505, South Korea

Location

Related Publications (2)

• Chitti B, Pham A, Marcott S, Wang X, Potters L, Wernicke AG, Parashar B. Temporal Changes in Esophageal Cancer Mortality by Geographic Region: A Population-based Analysis. Cureus. 2018 Nov 15;10(11):e3596. doi: 10.7759/cureus.3596.

  PMID: 30680257 BACKGROUND

• Murphy G, McCormack V, Abedi-Ardekani B, Arnold M, Camargo MC, Dar NA, Dawsey SM, Etemadi A, Fitzgerald RC, Fleischer DE, Freedman ND, Goldstein AM, Gopal S, Hashemian M, Hu N, Hyland PL, Kaimila B, Kamangar F, Malekzadeh R, Mathew CG, Menya D, Mulima G, Mwachiro MM, Mwasamwaja A, Pritchett N, Qiao YL, Ribeiro-Pinto LF, Ricciardone M, Schuz J, Sitas F, Taylor PR, Van Loon K, Wang SM, Wei WQ, Wild CP, Wu C, Abnet CC, Chanock SJ, Brennan P. International cancer seminars: a focus on esophageal squamous cell carcinoma. Ann Oncol. 2017 Sep 1;28(9):2086-2093. doi: 10.1093/annonc/mdx279.

  PMID: 28911061 BACKGROUND

MeSH Terms

Conditions

Esophageal Neoplasms

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Study Officials

• Sook Ryun Park, MD, Ph.D.

  Asan Medical Center

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: July 14, 2020
• First Posted: July 31, 2020
• Study Start: September 7, 2020
• Primary Completion: December 31, 2025
• Study Completion (Estimated): December 31, 2026
• Last Updated: April 20, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)