A Phase II Study of PD-1/IL-2α-bias Bispecific Antibody Fusion Protein Monotherapy in Advanced Esophageal Squamous Cell Carcinoma After Failure of Prior ICI Plus Platinum-Based Chemotherapy

Official title

A Prospective, Single-Arm, Phase II Study to Evaluate the Efficacy and Safety of PD-1/IL-2α-bias Bispecific Antibody Fusion Protein Monotherapy in Patients With Advanced or Metastatic Esophageal Squamous Cell Carcinoma After Failure of Prior Immune Checkpoint Inhibitor Plus Platinum-Based Chemotherapy

Overview

Effective later-line treatment options remain an unmet medical need for patients with advanced esophageal squamous cell carcinoma (ESCC) whose disease has progressed after prior immunotherapy, particularly given the widespread use of immunotherapy in the first-line setting. This study is designed to evaluate the efficacy and safety of PD-1/IL-2α-bias bispecific antibody fusion protein monotherapy in patients with advanced or metastatic ESCC after failure of prior immune checkpoint inhibitor (ICI) plus platinum-based chemotherapy.

Interventions

• Drug PD-1/IL-2α-bias bispecific antibody fusion protein
  PD-1/IL-2α-bias bispecific antibody fusion protein: administered according to protocol-defined procedure

Primary outcome measures

• Objective Response Rate [Time frame: The first tumor assessment will be performed 7 weeks (±7 days) after the first dose; thereafter, tumor assessments will be performed every 6 weeks (±7 days) until 1 year (54 weeks), and then every 12 weeks (±7 days) thereafter]

Secondary outcome measures (8)

• Disease Control Rate [Time frame: Up to 24 months]
• Progression Free Survival [Time frame: Up to 24 months]
• Overall Survival [Time frame: From date of first dose until the date of death from any cause, whichever came first, assessed up to 2 years after the last patient is enrolled.]
• Incidence of Adverse Events (AE) [Time frame: Up to 24 months]
• Incidence of treatment-emergent adverse Events (TEAE) [Time frame: Up to 24 months]
• Incidence of treatment-related adverse Events (TRAE) [Time frame: Up to 24 months]
• Incidence of Immune-related adverse Events (irAE) [Time frame: Up to 24 months]
• Incidence of serious adverse events (SAE) [Time frame: Up to 24 months]

Eligibility criteria

Inclusion criteria

• Histologically or cytologically confirmed unresectable locally advanced or metastatic esophageal squamous cell carcinoma (ESCC)
• Disease progression or treatment failure after prior immune checkpoint inhibitor (ICI) plus platinum-based chemotherapy
• At least one measurable lesion according to RECIST version 1.1;
• ECOG PS 0 to 1;
• Age 18 to 75 years
• 6.Life expectancy of ≥12 weeks.
• Signed informed consent prior to study entry and willingness/ability to comply with study treatment, visits, and other protocol-specified procedures
• Adequate organ function
• Women of childbearing potential, or male patients whose sexual partners are women of childbearing potential, must use effective contraception throughout the treatment period and for 180 days after the last dose of study drug.

Exclusion criteria

• Histology showing mixed squamous cell carcinoma, including but not limited to adenosquamous carcinoma, squamous cell carcinoma with small cell carcinoma components, carcinosarcoma, or sarcomatoid carcinoma.
• Concurrent participation in another interventional clinical study, except for observational (non-interventional) studies or the follow-up phase of an interventional study.
• Has received any treatment that is explicitly prohibited by the protocol.
• Subjects with unresolved > Grade 1 toxicity associated with any prior antineoplastic therapy, with the exception of persistent Grade 2 alopecia, anemia, peripheral neuropathy, correctable electrolyte abnormalities, or stable endocrine abnormalities controlled with hormone replacement therapy.
• Prior immune checkpoint inhibitor therapy permanently discontinued due to severe immune-related toxicity.
• Clinically significant physical examination findings or laboratory abnormalities that, in the investigator's judgment, may interfere with study results or increase the risk of treatment-related complications.
• Women who are pregnant or lactating
• Active autoimmune disease or history of autoimmune disease
• Known positive HIV test, active hepatitis B, hepatitis C (HCV), tuberculosis, or a history of these infections.
• Clinically significant cardiovascular or cerebrovascular disease.
• History of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis requiring corticosteroid therapy, or any clinically evident active interstitial lung disease; idiopathic pulmonary fibrosis identified on baseline CT scan; or uncontrolled massive pleural effusion or pericardial effusion.
• Uncontrolled or unstable intercurrent illness
• For subjects with uncontrolled epilepsy, central nervous system disease, or mental illness, the investigator should assess whether such conditions may impair the subject's ability to provide informed consent or comply with the study protocol.
• Poor gastrointestinal function, malabsorption syndrome, or active gastrointestinal ulcer.
• History of organ transplantation or allogeneic hematopoietic stem cell transplantation.
• Congenital or acquired immunodeficiency.
• Severe malnutrition requiring parenteral nutrition support, except for malnutrition corrected for more than 4 weeks before the first dose of study treatment.
• Uncontrolled metabolic disorder or other non-malignant organic/systemic disease or secondary effect of cancer that may result in high medical risk and/or uncertainty in survival assessment.
• Hepatic encephalopathy, hepatorenal syndrome, or Child-Pugh class B or higher cirrhosis.
• History of intestinal obstruction, inflammatory bowel disease, extensive bowel resection (partial colectomy or extensive small bowel resection with chronic diarrhea), Crohn's disease, ulcerative colitis, chronic diarrhea, or any other acute/chronic disease, psychiatric disorder, or laboratory abnormality that may increase study risk, interfere with interpretation of results, or, in the investigator's judgment, make the patient unsuitable for study participation.
• Another pathologically confirmed malignancy diagnosed within 5 years before the first dose, except for curatively treated basal-cell carcinoma of the skin, squamous-cell carcinoma of the skin, and/or carcinoma in situ after curative resection, localized prostate cancer after radical treatment, papillary thyroid carcinoma, and other malignancies that have been curatively treated, have had no known active disease for at least 2 years before study entry, and have an extremely low risk of recurrence.
• Interstitial pneumonitis, pulmonary fibrosis, pneumoconiosis, drug-related pneumonitis, radiation pneumonitis, or other pulmonary conditions requiring corticosteroids or other treatment; history of severely impaired pulmonary function or other forms of restrictive lung disease.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Beijing GoBroad Hospital — Beijing

Publications

• Wang ZX, Cui C, Yao J, Zhang Y, Li M, Feng J, Yang S, Fan Y, Shi J, Zhang X, Shen L, Shu Y, Wang C, Dai T, Mao T, Chen L, Guo Z, Liu B, Pan H, Cang S, Jiang Y, Wang J, Ye M, Chen Z, Jiang D, Lin Q, Ren W, Wang J, Wu L, Xu Y, Miao Z, Sun M, Xie C, Liu Y, Wang Q, Zhao L, Li Q, Huang C, Jiang K, Yang K, Li D, Liu Y, Zhu Z, Chen R, Jia L, Li W, Liao W, Liu HX, Ma D, Ma J, Qin Y, Shi Z, Wei Q, Xiao K, PMID 35245446
• Lu Z, Wang J, Shu Y, Liu L, Kong L, Yang L, Wang B, Sun G, Ji Y, Cao G, Liu H, Cui T, Li N, Qiu W, Li G, Hou X, Luo H, Xue L, Zhang Y, Yue W, Liu Z, Wang X, Gao S, Pan Y, Galais MP, Zaanan A, Ma Z, Li H, Wang Y, Shen L; ORIENT-15 study group. Sintilimab versus placebo in combination with chemotherapy as first line treatment for locally advanced or metastatic oesophageal squamous cell carcinoma (OR PMID 35440464
• Luo H, Lu J, Bai Y, Mao T, Wang J, Fan Q, Zhang Y, Zhao K, Chen Z, Gao S, Li J, Fu Z, Gu K, Liu Z, Wu L, Zhang X, Feng J, Niu Z, Ba Y, Zhang H, Liu Y, Zhang L, Min X, Huang J, Cheng Y, Wang D, Shen Y, Yang Q, Zou J, Xu RH; ESCORT-1st Investigators. Effect of Camrelizumab vs Placebo Added to Chemotherapy on Survival and Progression-Free Survival in Patients With Advanced or Metastatic Esophageal Sq PMID 34519801
• Sun JM, Shen L, Shah MA, Enzinger P, Adenis A, Doi T, Kojima T, Metges JP, Li Z, Kim SB, Cho BC, Mansoor W, Li SH, Sunpaweravong P, Maqueda MA, Goekkurt E, Hara H, Antunes L, Fountzilas C, Tsuji A, Oliden VC, Liu Q, Shah S, Bhagia P, Kato K; KEYNOTE-590 Investigators. Pembrolizumab plus chemotherapy versus chemotherapy alone for first-line treatment of advanced oesophageal cancer (KEYNOTE-590): a PMID 34454674
• Rustgi AK, El-Serag HB. Esophageal carcinoma. N Engl J Med. 2014 Dec 25;371(26):2499-509. doi: 10.1056/NEJMra1314530. No abstract available. PMID 25539106
• Han B, Zheng R, Zeng H, Wang S, Sun K, Chen R, Li L, Wei W, He J. Cancer incidence and mortality in China, 2022. J Natl Cancer Cent. 2024 Feb 2;4(1):47-53. doi: 10.1016/j.jncc.2024.01.006. eCollection 2024 Mar. PMID 39036382

Identifiers

NCT: NCT07688291 · BJGBYY-IIT-LCYJ-2026-030

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗