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Advanced Lung Non-Small Cell CarcinomaPhase 2NCT04396535

Docetaxel With or Without Bintrafusp Alfa for the Treatment of Advanced Non-small Cell Lung Cancer

A Phase 2 study testing Bintrafusp Alfa and Docetaxel in people with Advanced Lung Non-Small Cell Carcinoma and Stage III Lung Cancer AJCC v8, run by Mayo Clinic at 3 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This phase II trial studies how well docetaxel works with or without bintrafusp alfa in treating patients with non-small cell lung cancer that has spread to other places in the body (advanced). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Bintrafusp Alfa and Docetaxel
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
10 participants
Where
3 sitesUnited States
Study dates
23 Oct 2020to 31 Dec 2023
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

  • Age >= 18 years
  • Histological confirmation of non-small cell lung cancer (NSCLC) with advanced disease
  • Prior treatment required:
  • Anti-PD1/PD-L1 agent in combination with platinum-based chemotherapy
  • Measurable disease
  • NOTE: Tumor lesions in a previously irradiated area are not considered measurable disease; Disease that is measurable by physical examination only is not eligible
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  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2
  • Hemoglobin >= 9.0 g/dL (obtained =< 14 days prior to registration)
  • Absolute neutrophil count (ANC) >= 1500/mm^3 (obtained =< 14 days prior to registration)
  • Platelet count >= 100,000/mm^3 (obtained =< 14 days prior to registration)
  • Total bilirubin =< upper limit of normal (ULN) (obtained =< 14 days prior to registration)
  • Alanine aminotransferase (ALT/serum glutamate pyruvate transaminase [SGPT]) and aspartate transaminase (AST/serum glutamic-oxaloacetic transaminase [SGOT]) =< 1.5 x ULN (obtained =< 14 days prior to registration)
  • Alkaline phosphatase <= 2.5 x ULN (obtained =< 14 days prior to registration)
  • Prothrombin time (PT)/international normalized ratio (INR)/activated partial thromboplastin time (aPTT) =< 1.5 x ULN OR if patient is receiving anticoagulant therapy INR or aPTT is within target range of therapy (obtained =< 14 days prior to registration)
  • Calculated creatinine clearance >= 30 ml/min using the Cockcroft-Gault formula (obtained =< 14 days prior to registration)
  • Negative pregnancy test done =< 7 days prior to registration, for persons of childbearing potential only
  • NOTE: If a urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
  • Willing to use birth control as follows:
  • If able to become pregnant: Willing to use birth control during treatment and for 6 months after last dose of docetaxel and/or bintrafusp alfa, whichever is later
  • If able to father a child: Willing to use birth control with partners able to become pregnant during treatment and for 3 months after last dose of docetaxel and/or bintrafusp alfa, whichever is later
  • Provide written informed consent
  • Willingness to provide mandatory blood specimens for correlative research
  • Willingness to provide mandatory tissue specimens for correlative research
  • Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study)
  • CROSSOVER ELIGIBILITY: Documented disease progression =< 28 days prior to crossover registration
  • CROSSOVER ELIGIBILITY: No contraindications to bintrafusp alfa at the time of crossover registration
  • CROSSOVER ELIGIBILITY: Patient and physician agree to try crossover treatment with bintrafusp alfa
  • CROSSOVER ELIGIBILITY: Provide written informed consent

Who cannot join

  • Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown:
  • Pregnant persons
  • Nursing persons
  • Persons of childbearing potential who are unwilling to employ adequate contraception
  • Any of the following prior therapies:
  • Surgery =< 4 weeks prior to registration
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  • Chemotherapy =< 4 weeks prior to registration
  • Received single agent anti-PD1/PD-L1 as first line therapy for metastatic disease
  • Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
  • Uncontrolled intercurrent illness including, but not limited to:
  • Ongoing or active infection
  • Symptomatic congestive heart failure
  • Unstable angina pectoris
  • Cardiac arrhythmia
  • Or psychiatric illness/social situations that would limit compliance with study requirements
  • Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm
  • Other active malignancy =< 5 years prior to registration
  • EXCEPTIONS: Non-melanotic skin cancer or carcinoma-in-situ of the cervix
  • NOTE: If there is a history of prior malignancy, they must not be receiving other specific treatment for their cancer
  • History of myocardial infarction =< 6 months, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
  • Known primary central nervous system (CNS) malignancy or symptomatic CNS metastases are excluded, with the following exceptions:
  • Patients with asymptomatic untreated CNS disease may be enrolled, provided all of the following criteria are met:
  • Evaluable or measurable disease outside the CNS
  • No metastases to brain stem, midbrain, pons, medulla, cerebellum, or within 10 mm of the optic apparatus (optic nerves and chiasm)
  • No history of intracranial hemorrhage or spinal cord hemorrhage
  • No ongoing requirement for dexamethasone for CNS disease; patients on a stable dose of anticonvulsants are permitted
  • No neurosurgical resection or brain biopsy =< 28 days prior to registration
  • Patients with asymptomatic treated CNS metastases may be enrolled, provided all the criteria listed above are met as well as the following:
  • Radiographic demonstration of improvement upon the completion of CNS-directed therapy and no evidence of interim progression between the completion of CNS-directed therapy and the screening radiographic study
  • No stereotactic radiation or whole-brain radiation =< 28 days prior to registration
  • Screening CNS radiographic study >= 4 weeks from completion of radiotherapy and >= 2 weeks from discontinuation of corticosteroids
  • History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
  • History or current evidence of bleeding disorder, including bleeding diathesis, i.e., any hemorrhage/bleeding event of Common Terminology Criteria for Adverse Events (CTCAE) grade >= 2 in =< 28 days prior to registration
  • Taking oral prednisone of >= 10 mg daily or equivalent
  • Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis; fatty liver; and inherited liver disease. Notes:
  • Patients with past or resolved hepatitis B infection (defined as having a negative hepatitis B surface antigen [HBsAg] test and a positive anti-HBc [antibody to hepatitis B core antigen] antibody test) are eligible
  • Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV ribonucleic acid (RNA)
  • History or risk of autoimmune disease, including, but not limited to, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjogren's syndrome, Bell's palsy, Guillain-Barre syndrome, multiple sclerosis, autoimmune thyroid disease, vasculitis, or glomerulonephritis. Notes:
  • Patients with a history of autoimmune hypothyroidism on a stable dose of thyroid replacement hormone are eligible
  • Patients with controlled type 1 diabetes mellitus on a stable insulin regimen are eligible
  • Patients with eczema, psoriasis, lichen simplex chronicus of vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis would be excluded) are permitted provided that they meet the following conditions:
  • Patients with psoriasis must have a baseline ophthalmologic exam to rule out ocular manifestations
  • Rash must cover less than 10% of body surface area (BSA)
  • Disease is well controlled at baseline and only requiring low potency topical steroids (e.g., hydrocortisone 2.5%, hydrocortisone butyrate 0.1%, fluocinolone 0.01%, desonide 0.05%, alclometasone dipropionate 0.05%)
  • No acute exacerbations of underlying condition within the last 12 months (not requiring psoralen plus ultraviolet A radiation [PUVA], methotrexate, retinoids, biologic agents, oral calcineurin inhibitors; high potency or oral steroids)
  • Known active human immunodeficiency virus (HIV) infection (defined as patients who are not on anti-retroviral treatment and have detectable viral load and CD4+ < 500/ml)
  • NOTE: HIV-positive patients who are well controlled on anti-retroviral therapy are allowed to enroll
  • History of idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis on screening chest computed tomography (CT) scan. Note: History of radiation pneumonitis in the radiation field (fibrosis) is permitted
  • Severe infections =< 4 weeks prior to registration, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia
  • History of peripheral neuropathy >= grade 2
  • Known hypersensitivity to docetaxel or polysorbate 80

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • Mayo Clinic in Florida

    Jacksonville, Florida, 32224-9980

  • Mayo Clinic in Rochester

    Rochester, Minnesota, 55905

  • Mayo Clinic in Arizona

    Scottsdale, Arizona, 85259

Other trials in United States

About this study

Official title: Randomized Phase II Study of Standard Chemotherapy With Docetaxel With or Without Bintrafusp Alfa in Patients With Advanced NSCLC After Progressing on a Combination of Anti-PD-1/PD-L1 Agents and Chemotherapy

This phase II trial studies how well docetaxel works with or without bintrafusp alfa in treating patients with non-small cell lung cancer that has spread to other places in the body (advanced). Chemotherapy drugs, such as docetaxel, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with bintrafusp alfa, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Giving docetaxel and bintrafusp alfa in combination may work better in treating non small-cell lung cancer compared to docetaxel alone.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To compare the progression-free survival (PFS) of bintrafusp alfa in combination with docetaxel versus (vs) docetaxel alone.

SECONDARY OBJECTIVES:

  1. To evaluate overall survival of bintrafusp alfa in combination with docetaxel vs docetaxel alone.

II. To evaluate overall response rates of bintrafusp alfa in combination with docetaxel vs docetaxel alone.

III. To evaluate duration of response of bintrafusp alfa in combination with docetaxel vs docetaxel alone.

IV. To evaluate the safety of bintrafusp alfa in combination with docetaxel vs docetaxel alone.

CORRELATIVE RESEARCH OBJECTIVES:

  1. To evaluate PD-L1, TGF-beta, and TMB as potential predictive markers of clinical response in tumor biopsies and in plasma.

II. To evaluate biomarkers associated with inhibition of TGF-beta and PD-L1. III. To evaluate the changes in immune system using mass cytometry in response to TGF-beta and PD-L1 inhibition.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive docetaxel intravenously (IV) over 1 hour and bintrafusp alfa IV over 60 minutes on day 1. Treatment repeats every 3 weeks for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive bintrafusp alfa IV over 60 minutes on day 1. Cycles repeat every 3 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive docetaxel IV over 1 hour on day 1. Cycles repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Patients who experience disease progression may crossover to Arm I and receive bintrafusp alfa alone.

After completion of study treatment, patients are followed up at 30 days and then every 3 months for 5 years.

Being tested
Bintrafusp Alfa, Docetaxel
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

  • DocetaxelDrug

    Also called Docecad, RP56976, Taxotere, Taxotere Injection Concentrate

    Given IV

Study groups in NCT04396535
Study groupRoleWhat they receive
Arm I (docetaxel, bintrafusp alfa)ExperimentalPatients receive docetaxel IV over 1 hour and bintrafusp alfa IV over 60 minutes on day 1. Treatment repeats every 3 weeks for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive bintrafusp alfa IV over 60 minutes on day 1. Cycles repeat every 3 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Bintrafusp Alfa; Drug: Docetaxel
Arm II (docetaxel)Active comparatorPatients receive docetaxel IV over 1 hour on day 1. Cycles repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Patients who experience disease progression may crossover to Arm I and receive bintrafusp alfa alone.
Receives: Drug: Docetaxel

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression-free Survival (PFS) of Bintrafusp Alfa in Combination With Docetaxel Versus (vs) Docetaxel Alone

    The primary analysis of PFS will be a comparison of the Kaplan-Meier curves for docetaxel + bintrafusp alfa vs. docetaxel alone using a one-sided log-rank test.

    Measured: From randomization to the first of either disease progression or death from any cause, assessed up to 3 years and 2 months

Secondary outcomes (4)

  1. Overall Survival (OS)

    OS will be estimated using the Kaplan-Meier method, where the log-rank test will be used to compare the 2 treatment arms.

    Measured: From study entry to death from any cause, assessed up to 3 years and 2 months

  2. Confirmed Response Rates

    Will be classified as a confirmed response per the Immune-Modified Response Evaluation Criteria in Solid Tumors (iRECIST) criteria, if they have a partial or complete response for 2 consecutive evaluations at least 4 weeks apart. The proportion of patients with a confirmed response will be calculated and compared between the 2 arms using a Chi-square of Fisher's Exact test.

    Measured: Up to 3 years and 2 months

  3. Duration of Response

    The duration of confirmed responses will be assessed using the Kaplan Meier method, where the duration of confirmed response will be defined as the time from the first documented date of response (complete response [CR] or partial response [PR]) to the date at which progression is first documented. Duration of response will be estimated using the Kaplan-Meier method, where the log-rank test will be used to compare the 2 treatment arms.

    Measured: Up to 3 years and 2 months

  4. Incidence of Adverse Events

    The maximum grade for each type of adverse event will be summarized using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The frequency and percentage of grade 3+ adverse events will be compared between the 2 treatment arms. Comparisons between arms will be made by using either the Chi-square or Fisher's Exact test.

    Measured: Up to 3 years and 2 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 May 2020
  2. Study start23 Oct 2020
  3. Primary completion31 Dec 2023
  4. Study completion31 Dec 2023

Why it stopped: EMD Serono recommendation based on three other studies that failed to show benefit for bintrafusp alfa

Resources

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
Randomised
Intervention model
Crossover
Masking
None (open label)
Enrolment
10 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04396535
Sponsor's protocol ID
MC1821
Other IDs
NCI-2020-02975, MC1821, 19-010887
Status last verified
Jan 2024
First submitted
14 May 2020
Last updated
17 Nov 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Bintrafusp Alfa and Docetaxel in people with Advanced Lung Non-Small Cell Carcinoma and Stage III Lung Cancer AJCC v8, run by Mayo Clinic at 3 sites 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 28 inclusion and 51 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 17 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites 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 17 Nov 2025). 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?

Progression-free Survival (PFS) of Bintrafusp Alfa in Combination With Docetaxel Versus (vs) Docetaxel Alone (time frame: From randomization to the first of either disease progression or death from any cause, assessed up to 3 years and 2 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04396535.

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 17 Nov 2025.

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