Clinical Trials /

Bintrafusp Alfa Before Surgery for the Treatment of Untreated Resectable Non-small Cell Lung Cancer

NCT04560686

Description:

This phase II trial studies how well bintrafusp alfa before surgery works in treating patients with non-small cell lung cancer for which the patient has not received treatment in the past (untreated) and that can be removed by surgery (resectable). Immunotherapy with bintrafusp alfa may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving bintrafusp alfa before surgery may help lower the risk of the cancer coming back after surgery.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Bintrafusp Alfa Before Surgery for the Treatment of Untreated Resectable Non-small Cell Lung Cancer
  • Official Title: Phase II Study of Neoadjuvant Immune Checkpoint Blockade-Based Therapy With M7824 (Bintrafusp Alpha) for Untreated Resectable Non-Small Cell Lung Cancers

Clinical Trial IDs

  • ORG STUDY ID: 2019-0910
  • SECONDARY ID: NCI-2020-03769
  • SECONDARY ID: 2019-0910
  • NCT ID: NCT04560686

Conditions

  • Resectable Lung Non-Small Cell Carcinoma
  • Stage I Lung Cancer AJCC v8
  • Stage IA1 Lung Cancer AJCC v8
  • Stage IA2 Lung Cancer AJCC v8
  • Stage IA3 Lung Cancer AJCC v8
  • Stage IB Lung Cancer AJCC v8
  • Stage II Lung Cancer AJCC v8
  • Stage IIA Lung Cancer AJCC v8
  • Stage IIB Lung Cancer AJCC v8
  • Stage IIIA Lung Cancer AJCC v8
  • Stage IIIB Lung Cancer AJCC v8

Interventions

DrugSynonymsArms
Bintrafusp AlfaAnti-PDL1/TGFb Trap MSB0011359C, M7824, MSB0011359CTreatment (bintrafusp alfa, surgical resection)

Purpose

This phase II trial studies how well bintrafusp alfa before surgery works in treating patients with non-small cell lung cancer for which the patient has not received treatment in the past (untreated) and that can be removed by surgery (resectable). Immunotherapy with bintrafusp alfa may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving bintrafusp alfa before surgery may help lower the risk of the cancer coming back after surgery.

Detailed Description

      PRIMARY OBJECTIVE:

      I. To evaluate the rate of major pathologic response (MPR).

      OUTLINE:

      Patients receive bintrafusp alfa intravenously (IV) on days 1, 15, and 29 in the absence of
      unacceptable toxicity. Within 4-6 weeks after last dose of bintrafusp alfa, patients undergo
      surgery at the discretion of the treating surgeon. Within 8 weeks after surgery, patients may
      receive chemotherapy or undergo radiation therapy at the discretion of the treating
      physician.

      After completion of study treatment, patients are followed for up to 5 years.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (bintrafusp alfa, surgical resection)ExperimentalPatients receive bintrafusp alfa IV on days 1, 15, and 29 in the absence of unacceptable toxicity. Within 4-6 weeks after last dose of bintrafusp alfa, patients undergo surgery at the discretion of the treating surgeon. Within 8 weeks after surgery, patients may receive chemotherapy or undergo radiation therapy at the discretion of the treating physician.
  • Bintrafusp Alfa

Eligibility Criteria

        Inclusion Criteria:

          -  Histologically or cytologically confirmed previously untreated non-small cell lung
             cancer (NSCLC). If a diagnostic biopsy is available, a pre-treatment biopsy is not
             required. Patients with a suspected lung cancer are eligible, but pathology must be
             confirmed prior to initiating treatment on study. Neuroendocrine carcinomas (e.g.
             small cell lung cancer [SCLC], large cell neuroendocrine carcinoma, atypical
             carcinoid, carcinoid) are not eligible. Non-small cell carcinomas with neuroendocrine
             differentiation are eligible

          -  Patients with stage I-IIIA disease and IIIB (T3N2 only, and N2 single station),
             according to American Joint Committee on Cancer (AJCC) 8th edition, are eligible for
             arm A of the study. Patients with stage III, N2 single station, must not have more
             than one mediastinal lymph node station involved by tumor

          -  All patients must have lymph node evaluation of contralateral stations 2 and/or 4 to
             exclude N3 disease

          -  The patient must be a suitable candidate for surgery, in the opinion of the treating
             physician

          -  Predicted forced expiratory volume in 1 second (FEV1) >= 50%

          -  Predicted carbon monoxide diffusing capability test (DLCO) >= 50%

          -  Signed and dated written informed consent must be provided by the patient prior to
             admission to the study in accordance with International Conference on Harmonisation
             Good Clinical Practice (ICH-GCP) guidelines and to the local

          -  Eastern Cooperative Oncology Group (ECOG) performance status score 0-1

          -  Absolute neutrophil count (ANC): >= 1.5 X 10^9 /L

          -  Hemoglobin: >= 9.0 g/dL

          -  Platelets >= 100 X 10^9 /L

          -  Total bilirubin: =< 1.5 X upper limit of normal (ULN) (except subjects with Gilbert
             Syndrome, who can have total bilirubin < 3.0 mg/dL)

          -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT): =< 3 X ULN

          -  Creatinine: =< 1.5 X ULN or calculated creatinine clearance: >= 50 mL/min or 24-hour
             urine creatinine clearance: >= 50 mL/min

        Exclusion Criteria:

          -  Mixed SCLC and NSCLC histology

          -  Major surgery within 4 weeks prior to the first dose of study intervention

          -  Thoracic radiation therapy (RT) of > 30 Gy within 6 months prior to the first dose of
             study intervention.

          -  Prior systemic therapy, including treatment with anti-PD-1/PD-L1 therapies and M7824,
             for treatment of the current lung cancer

          -  Currently receiving cancer therapy (chemotherapy, radiation therapy, immunotherapy, or
             biologic therapy) or investigational anti-cancer drug

          -  Previous malignant disease (other than the target malignancy to be investigated in
             this study) within the last 2 years. Participants with a history of cervical carcinoma
             in situ, superficial or noninvasive bladder cancer, or basal cell or squamous cell
             carcinoma in situ previously treated with curative intent are NOT excluded.
             Participants with other localized malignancies treated with curative intent need to be
             discussed with the principal investigator (PI) of the study

          -  Receipt of any organ transplantation, including allogeneic stem-cell transplantation,
             but with the exception of transplants that do not require immunosuppression (e.g.,
             corneal transplant, hair transplant)

          -  Has interstitial lung disease (ILD) OR has had a history of pneumonitis that has
             required oral or IV steroids

          -  Pregnant or lactating female:

               -  Women of childbearing potential (WOCB) must have a negative serum or urine
                  pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human
                  chorionic gonadotropin [HCG]) within 72 hours prior to the start of
                  immunotherapy.

               -  Women of childbearing potential is defined as any female who has experienced
                  menarche and who has not undergone surgical sterilization (hysterectomy or
                  bilateral oophorectomy) or who is not postmenopausal. Menopause is defined
                  clinically as 12 months of amenorrhea in a woman over 45 in the absence of other
                  biological or physiological causes

          -  Unwillingness or inability to follow the procedures required in the protocol

          -  Any serious or uncontrolled medical disorder that, in the opinion of the investigator,
             may increase the risk associated with study participation or study drug
             administration, impair the ability of the subject to receive protocol therapy, or
             interfere with the interpretation of study results. Participants with history of
             bleeding diathesis or recent major bleeding events considered by the Investigator as
             high risk for investigational drug treatment are also excluded

          -  Subjects with active, known or suspected autoimmune disease. Subjects with vitiligo,
             type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only
             requiring hormone replacement, psoriasis not requiring systemic treatment, or
             conditions not expected to recur in the absence of an external trigger are permitted
             to enroll

          -  Subjects with a condition requiring systemic treatment with either corticosteroids (>
             10 mg daily prednisone equivalents) or other immunosuppressive medications within 14
             days of study drug administration. Inhaled or topical steroids and adrenal replacement
             doses > 10 mg daily prednisone equivalents are permitted in the absence of active
             autoimmune disease

          -  Subjects are permitted to use topical, ocular, intra-articular, intranasal, and
             inhalational corticosteroids (with minimal systemic absorption). Physiologic
             replacement doses of systemic corticosteroids are permitted, even if > 10 mg/day
             prednisone equivalents. 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

          -  History of positive hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus
             ribonucleic acid indicating acute or chronic infection

          -  History of positive human immunodeficiency virus or known acquired immunodeficiency
             syndrome

          -  History of severe hypersensitivity reaction to any monoclonal antibody and/or to study
             drug components, any history of anaphylaxis, or recent (within 5 months) history of
             uncontrolled asthma

          -  Serious illness or concomitant non-oncological disease such as neurologic,
             psychiatric, infectious disease or laboratory abnormality that may increase the risk
             associated with study participation or study drug administration and in the judgment
             of the investigator would make the patient inappropriate for entry into the study

          -  Vaccine administration within 4 weeks of M7824 administration. Vaccination with live
             vaccines while on trial is prohibited. Administration of inactivated vaccines is
             allowed (for example, inactivated influenza vaccines)

          -  Patients who are sexually active, with preserved reproductive capacity, and unwilling
             to use a medically acceptable method of contraception (e.g. such as implants,
             injectables, combined oral contraceptives, some intrauterine devices or vasectomized
             partner for participating females, condoms for participating males) during and after
             the trial as detailed below:

               -  WOCBP should use an adequate method to avoid pregnancy for 65 days after the last
                  dose of investigational drug.

               -  Men who are sexually active with WOCBP must use any contraceptive method with a
                  failure rate of less than 1% per year.

               -  Men receiving immunotherapy and who are sexually active with WOCBP will be
                  instructed to adhere to contraception for a period of 125 days after the last
                  dose of investigational product.

               -  Women who are not of childbearing potential as well as azoospermic men do not
                  require contraception

          -  Psychological, familial, sociological or geographical factors potentially hampering
             compliance with the study protocol and follow-up schedule
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Major pathologic response (MPR)
Time Frame:At time of surgery
Safety Issue:
Description:MPR will be defined as =< 10% viable tumor cells in the resected specimen using the methods described by Pataer et al. Will estimate the MPR rate with a 95% credible interval (CI) assuming that the MPR rate follows a prior beta distribution (0.5, 0.5) with one patient worth of information.

Secondary Outcome Measures

Measure:Incidence of adverse events
Time Frame:Up to 1 year
Safety Issue:
Description:Assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.
Measure:Peri-operative morbidity and mortality
Time Frame:Up to 1 year
Safety Issue:
Description:
Measure:Response rates to induction
Time Frame:Up to 5 years post-treatment
Safety Issue:
Description:Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
Measure:Recurrence-free survival
Time Frame:At 12 months
Safety Issue:
Description:Will be computed using the Kaplan-Meier method.
Measure:Recurrence-free survival
Time Frame:At 18 months
Safety Issue:
Description:Will be computed using the Kaplan-Meier method.
Measure:Recurrence-free survival
Time Frame:At 24 months
Safety Issue:
Description:Will be computed using the Kaplan-Meier method.
Measure:Overall survival
Time Frame:At 12 months
Safety Issue:
Description:Will be computed using the Kaplan-Meier method.
Measure:Overall survival
Time Frame:At 18 months
Safety Issue:
Description:Will be computed using the Kaplan-Meier method.
Measure:Overall survival
Time Frame:At 24 months
Safety Issue:
Description:Will be computed using the Kaplan-Meier method.
Measure:MPR
Time Frame:Up to 24 months
Safety Issue:
Description:Correlate MPR with recurrence-free and overall survival. Association analysis by Pearson or Spearman correlation coefficient will be calculated for continuous data and chisquare or Fisher's exact test for categorical data.
Measure:Complete resection rate
Time Frame:At time of surgery
Safety Issue:
Description:
Measure:Pathologic complete response
Time Frame:At time of surgery
Safety Issue:
Description:
Measure:CD8+ TILs in resected tumor tissue
Time Frame:At time of surgery
Safety Issue:
Description:Quantification of CD8+ TILs will be assessed by counting the cells positive for staining with an anti-CD8 antibody by immunohistochemistry and/or immunofluorescence in five random square areas (1 mm^2 each) in both intratumoral and peritumoral compartments using an automated system.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:M.D. Anderson Cancer Center

Last Updated

September 21, 2020