- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04560686
Bintrafusp Alfa Before Surgery for the Treatment of Untreated Resectable Non-small Cell Lung Cancer
Phase II Study of Neoadjuvant Immune Checkpoint Blockade-Based Therapy With M7824 (Bintrafusp Alpha) for Untreated Resectable Non-Small Cell Lung Cancers
Study Overview
Status
Conditions
- 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
- 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
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Texas
-
Houston, Texas, United States, 77030
- M D Anderson Cancer Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Treatment (bintrafusp alfa, surgical resection)
Patients 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.
|
Undergo surgery
Given IV
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Major Pathologic Response (MPR)
Time Frame: At time of surgery
|
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.
|
At time of surgery
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence of Adverse Events
Time Frame: Up to 1 year
|
Assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.
|
Up to 1 year
|
Peri-operative Morbidity and Mortality
Time Frame: Up to 1 year
|
Up to 1 year
|
|
Response Rates to Induction
Time Frame: Up to 5 years post-treatment
|
Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
|
Up to 5 years post-treatment
|
Recurrence-free Survival
Time Frame: At 12 months
|
Will be computed using the Kaplan-Meier method.
|
At 12 months
|
Recurrence-free Survival
Time Frame: At 18 months
|
Will be computed using the Kaplan-Meier method.
|
At 18 months
|
Recurrence-free Survival
Time Frame: At 24 months
|
Will be computed using the Kaplan-Meier method.
|
At 24 months
|
Overall Survival
Time Frame: At 12 months
|
Will be computed using the Kaplan-Meier method.
|
At 12 months
|
Overall Survival
Time Frame: At 18 months
|
Will be computed using the Kaplan-Meier method.
|
At 18 months
|
Overall Survival
Time Frame: At 24 months
|
Will be computed using the Kaplan-Meier method.
|
At 24 months
|
Complete Resection (RO) Rate
Time Frame: At time of surgery
|
Complete resection (R0) rate is defined as number of Participants that successfully underwent surgical resection with microscopically clear surgical margins.
|
At time of surgery
|
Number of Participants With Pathologic Complete Response
Time Frame: At time of surgery
|
Pathologic complete response (pCR) in resected tumor specimens.
pCR is defined as the absence of any viable residual tumor at the time of surgical resection in the primary lung lesion and lymph nodes, by central (core) pathology review.
|
At time of surgery
|
CD8+ TILs in Resected Tumor Tissue
Time Frame: At time of surgery
|
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.
|
At time of surgery
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Biomarker Analysis
Time Frame: Up to 5 years post-treatment
|
Multivariate analysis will be used to explore the role of biomarkers in predicting pathologic response to treatment, in an exploratory way.
|
Up to 5 years post-treatment
|
Collaborators and Investigators
Sponsor
Collaborators
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 2019-0910 (OTHER: M D Anderson Cancer Center)
- NCI-2020-03769 (REGISTRY: CTRP (Clinical Trial Reporting Program))
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Stage II Lung Cancer AJCC v8
-
University of California, San FranciscoBristol-Myers Squibb FoundationCompletedStage III 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 | Malignant Neoplasm | Stage III Colorectal Cancer AJCC v8 | Stage IIIA Colorectal Cancer AJCC v8 | Stage IIIB Colorectal... and other conditionsUnited States
-
Jonsson Comprehensive Cancer CenterBlue Note TherapeuticsTerminatedAnatomic Stage I Breast Cancer AJCC v8 | Anatomic Stage IA Breast Cancer AJCC v8 | Anatomic Stage IB Breast Cancer AJCC v8 | Anatomic Stage II Breast Cancer AJCC v8 | Anatomic Stage IIA Breast Cancer AJCC v8 | Anatomic Stage IIB Breast Cancer AJCC v8 | Anatomic Stage III Breast Cancer AJCC v8 | Anatomic... and other conditionsUnited States
-
City of Hope Medical CenterNational Cancer Institute (NCI)RecruitingLung Non-Small Cell Carcinoma | Stage III 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 | Stage III Colorectal Cancer AJCC v8 | Stage IIIA Colorectal Cancer AJCC v8 | Stage... and other conditionsUnited States
-
M.D. Anderson Cancer CenterRecruitingStage III Lung Cancer AJCC v8 | Lung Carcinoma | 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 | Stage I Lung Cancer AJCC v8 | Stage IA1 Lung Cancer AJCC v8 | Stage IA2 Lung Cancer AJCC v8 | Stage... and other conditionsUnited States
-
Roswell Park Cancer InstituteNational Cancer Institute (NCI)RecruitingStage 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 | 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...United States
-
City of Hope Medical CenterNational Cancer Institute (NCI)CompletedStage IVA Lung Cancer AJCC v8 | Stage IVB Lung Cancer AJCC v8 | Stage III Lung Cancer AJCC v8 | Metastatic Lung Carcinoma | Stage IV Lung Cancer AJCC v8 | Head and Neck Carcinoma | Lung Carcinoma | Stage II Lung Cancer AJCC v8 | Stage IIA Lung Cancer AJCC v8 | Stage IIB Lung Cancer AJCC v8 | Stage IIIA Lung... and other conditionsUnited States
-
City of Hope Medical CenterNational Cancer Institute (NCI)CompletedStage IVA Lung Cancer AJCC v8 | Stage IVB Lung Cancer AJCC v8 | Stage III Lung Cancer AJCC v8 | Stage IV 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 | Malignant Female... and other conditionsUnited States
-
University of Southern CaliforniaNational Cancer Institute (NCI); Genentech, Inc.RecruitingStage IVA Lung Cancer AJCC v8 | Stage IVB Lung Cancer AJCC v8 | Lung Non-Small Cell Carcinoma | Stage III Lung Cancer AJCC v8 | Stage IV 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... and other conditionsUnited States
-
Emory UniversityNational Cancer Institute (NCI)TerminatedLung Non-Small Cell Carcinoma | 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 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...United States
-
University of California, San FranciscoMerck Sharp & Dohme LLCWithdrawnLung Non-Small Cell Carcinoma | 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 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...United States
Clinical Trials on Therapeutic Conventional Surgery
-
Sidney Kimmel Cancer Center at Thomas Jefferson...CompletedSkin Basal Cell CarcinomaUnited States
-
City of Hope Medical CenterNational Cancer Institute (NCI)WithdrawnAdult Spinal Cord Neoplasm | Spinal Bone Metastases | Spinal Cord Metastases
-
University of California, DavisNational Cancer Institute (NCI)CompletedPain | Breast Cancer | Perioperative/Postoperative ComplicationsUnited States
-
AIDS Malignancy ConsortiumNational Cancer Institute (NCI); University of Arkansas; The Emmes Company, LLC; AIDS and Cancer Specimen ResourceActive, not recruitingHIV Infection | Anal Squamous Cell Carcinoma | Stage 0 Anal Canal Cancer | Stage I Anal Canal CancerUnited States
-
Alliance for Clinical Trials in OncologyNational Cancer Institute (NCI)UnknownBreast CancerUnited States
-
Roei Medical Technologies Ltd.Completed
-
SWOG Cancer Research NetworkNational Cancer Institute (NCI)Active, not recruitingBladder CancerUnited States, Canada
-
Institute of Cancer Research, United KingdomCompletedBladder CancerUnited Kingdom
-
Duke UniversityNational Cancer Institute (NCI)TerminatedUnspecified Adult Solid Tumor, Protocol Specific | Metastatic CancerUnited States
-
Alliance for Clinical Trials in OncologyNational Cancer Institute (NCI)CompletedBreast CancerUnited States