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

NCT04560686 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: 2019-0910NCI-2020-03769
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

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.

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

Outcome Measures

Primary Outcomes (1)

• Major Pathologic Response (MPR)

  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 Outcomes (12)

• Incidence of Adverse Events

  Up to 1 year

• Peri-operative Morbidity and Mortality

  Up to 1 year

• Response Rates to Induction

  Up to 5 years post-treatment

• Recurrence-free Survival

  At 12 months

• Recurrence-free Survival

  At 18 months

Other Outcomes (1)

• Biomarker Analysis

  Up to 5 years post-treatment

Study Arms (1)

Treatment (bintrafusp alfa, surgical resection)

EXPERIMENTAL

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.

Drug: Bintrafusp Alfa; Procedure: Therapeutic Conventional Surgery

Interventions

Bintrafusp Alfa DRUG

Given IV

Also known as: Anti-PDL1/TGFb Trap MSB0011359C, M7824, MSB0011359C

Treatment (bintrafusp alfa, surgical resection)

Therapeutic Conventional Surgery PROCEDURE

Undergo surgery

Treatment (bintrafusp alfa, surgical resection)

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Lung Neoplasms

Interventions

bintrafusp alfa protein, human

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Limitations and Caveats

Two participants were consented; one screen failure. The trial was terminated earlier than planned due to an administrative decision taken by the PI/co-PI in collaboration with the study sponsor based on emerging data made available with the investigational agent being tested in other diseases in the perioperative setting.

Results Point of Contact

• Title: Dr. Tina Cascone,MD- Assistant Professor, Thoracic-Head & Neck Med Onc
• Organization: UT MD Anderson Cancer Center

tcascone@mdanderson.org

(713) 792-6363

Study Officials

• Tina Cascone

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 24, 2020
• First Posted: September 23, 2020
• Study Start: August 5, 2020
• Primary Completion: July 1, 2021
• Study Completion: July 1, 2021
• Last Updated: July 28, 2022
• Results First Posted: July 28, 2022

Record last verified: 2022-07

Locations

US (1)