Resectable Lung Non-Small Cell CarcinomaPhase 2NCT04560686
Bintrafusp Alfa Before Surgery for the Treatment of Untreated Resectable Non-small Cell Lung Cancer
A Phase 2 study testing Bintrafusp Alfa and Therapeutic Conventional Surgery in people with Resectable Lung Non-Small Cell Carcinoma and Stage I Lung Cancer AJCC v8, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Resectable Lung Non-Small Cell Carcinoma, Stage I Lung Cancer AJCC v8, Stage IA1 Lung Cancer AJCC v8
- What is being tested?
- Bintrafusp Alfa and Therapeutic Conventional Surgery
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 1 siteUnited States
- Study dates
- 5 Aug 2020to 1 Jul 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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%
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase II Study of Neoadjuvant Immune Checkpoint Blockade-Based Therapy With M7824 (Bintrafusp Alpha) for Untreated Resectable Non-Small Cell Lung Cancers
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.
Read the detailed description
PRIMARY OBJECTIVE:
- 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.
- 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
- Being tested
- Bintrafusp Alfa, Therapeutic Conventional Surgery
- Medical subject headings
- Lung Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Bintrafusp AlfaDrug
Also called Anti-PDL1/TGFb Trap MSB0011359C, M7824, MSB0011359C
Given IV
Therapeutic Conventional SurgeryProcedure or surgery
Undergo surgery
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Bintrafusp Alfa; Procedure: Therapeutic Conventional Surgery |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: At time of surgery
Secondary outcomes (12)
Incidence of Adverse Events
Assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.
Measured: Up to 1 year
Peri-operative Morbidity and Mortality
Measured: Up to 1 year
Response Rates to Induction
Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
Measured: Up to 5 years post-treatment
Recurrence-free Survival
Will be computed using the Kaplan-Meier method.
Measured: At 12 months
Recurrence-free Survival
Will be computed using the Kaplan-Meier method.
Measured: At 18 months
Recurrence-free Survival
Will be computed using the Kaplan-Meier method.
Measured: At 24 months
Overall Survival
Will be computed using the Kaplan-Meier method.
Measured: At 12 months
Overall Survival
Will be computed using the Kaplan-Meier method.
Measured: At 18 months
Overall Survival
Will be computed using the Kaplan-Meier method.
Measured: At 24 months
Complete Resection (RO) Rate
Complete resection (R0) rate is defined as number of Participants that successfully underwent surgical resection with microscopically clear surgical margins.
Measured: At time of surgery
Number of Participants With Pathologic Complete Response
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.
Measured: At time of surgery
CD8+ TILs in Resected Tumor Tissue
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.
Measured: At time of surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Sep 2020
- Study start5 Aug 2020
- Primary completion1 Jul 2021
- Study completion1 Jul 2021
Why it stopped: Per PI Request
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Resectable Lung Non-Small Cell CarcinomaStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Tina Cascone, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04560686
- Sponsor's protocol ID
- 2019-0910
- Other IDs
- NCI-2020-03769, 2019-0910
- Status last verified
- Jul 2022
- First submitted
- 24 Jun 2020
- Last updated
- 28 Jul 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of Neoadjuvant Immune Checkpoint Blockade-Based Therapy With M7824 (Bintrafusp Alpha) for Untreated Resectable Non-Small Cell Lung Cancers
- ClinicalTrials.gov ID
- NCT04560686
- Acronym / sponsor ID
- 2019-0910
- 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
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Per PI Request
- Enrolment
- 2 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 5 Aug 2020 (actual)
- Primary completion
- 1 Jul 2021 (actual)
- Study completion
- 1 Jul 2021 (actual)
- First posted
- 23 Sep 2020 (actual)
- Results
- Posted 28 Jul 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (bintrafusp alfa, surgical resection) | Experimental | Drug: Bintrafusp Alfa, Procedure: Therapeutic Conventional SurgeryPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- 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%
Key exclusion criteria (27 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Bintrafusp AlfaAlso: Anti-PDL1/TGFb Trap MSB0011359C, M7824, MSB0011359CGiven IV | Drug | Treatment (bintrafusp alfa, surgical resection) |
| Therapeutic Conventional SurgeryUndergo surgery | Procedure or surgery | Treatment (bintrafusp alfa, surgical resection) |
Primary outcome
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.
12 secondary outcomes
Incidence of Adverse Events
Time frame: Up to 1 year
Peri-operative Morbidity and Mortality
Time frame: Up to 1 year
Response Rates to Induction
Time frame: Up to 5 years post-treatment
Recurrence-free Survival
Time frame: At 12 months
Recurrence-free Survival
Time frame: At 18 months
Recurrence-free Survival
Time frame: At 24 months
Overall Survival
Time frame: At 12 months
Overall Survival
Time frame: At 18 months
Overall Survival
Time frame: At 24 months
Complete Resection (RO) Rate
Time frame: At time of surgery
Number of Participants With Pathologic Complete Response
Time frame: At time of surgery
CD8+ TILs in Resected Tumor Tissue
Time frame: At time of surgery
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jul 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- University of Texas MD Anderson Cancer Center WebsiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Tina Cascone principal investigator
M.D. Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Bintrafusp Alfa and Therapeutic Conventional Surgery in people with Resectable Lung Non-Small Cell Carcinoma and Stage I Lung Cancer AJCC v8, run by M.D. Anderson Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 28 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Jul 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Major Pathologic Response (MPR) (time frame: At time of surgery). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jul 2022.