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Locally Advanced Lung Non-Squamous Non-Small Cell CarcinomaPhase 2NCT04971187

Bintrafusp Alfa With Chemotherapy for Tyrosine Kinase Inhibitor-Resistant EGFR-Mutant Non-small Cell Lung Cancer

A Phase 2 study testing Bintrafusp Alfa, Pemetrexed and Carboplatin in people with Locally Advanced Lung Non-Squamous Non-Small Cell Carcinoma and Metastatic Lung Non-Squamous Non-Small Cell Carcinoma, run by M.D. Anderson Cancer Center at 1 site 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 the effect of bintrafusp alfa with pemetrexed and platinum-based chemotherapy (carboplatin or cisplatin) in treating patients with EGFR mutant non-small cell lung cancer that have spread to nearby tissue or lymph nodes (locally advanced) or other places in the body (metastatic) and cannot… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Bintrafusp Alfa, Pemetrexed and Carboplatin
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
3 participants
Where
1 siteUnited States
Study dates
30 Jun 2021to 21 Feb 2022
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 equal or greater than 18 years old and willing to give their signed consent
  • Histologically or cytologically confirmed non-squamous, non-small cell lung cancer
  • Locally advanced or metastatic disease, not amenable to curative surgery or radiotherapy
  • Patients must have one of the following:
  • NSCLC which harbors EGFR Exon 19 deletion.
  • NSCLC which harbors EGFR L858R mutation.
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  • NSCLC which harbors EGFR G719X, S768X, L861X mutation, and other activating uncommon mutations in exon 18-21
  • NSCLC which harbors EGFR exon20 insertion
  • NSCLC which harbors EGFR T790M mutation EGFR deletion/mutation must be documented by a Clinical Laboratory Improvement Amendments (CLIA) certified test
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  • At least one target lesion, not previously irradiated and not chosen for biopsy during the study screening period, that can be accurately measured at baseline at equal or greater than 10 mm in the longest dimension by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
  • Patients must have received at least one line of EGFR tyrosine kinase inhibitor (TKI) treatment, if an Food and Drug Administration (FDA)-approved treatment exist for the EGFR mutation. Patients whose tumor harboring EGFR T790M mutation must have received prior osimertinib (or another EGFR TKI with demonstrated activity against T790M mutation). Patients who received more than one EGFR TKIs are eligible. Up to two lines of TKIs are allowed
  • Absolute neutrophil count (ANC) >= 1,500/mm^3 (obtained less than 4 weeks from study entry)
  • Platelet count >= 100,000/mm^3 (obtained less than 4 weeks from study entry)
  • Hemoglobin (HgB) >= 9 g/dL (obtained less than 4 weeks from study entry)
  • Creatinine =< 1.5 x upper limit of normal (ULN) (obtained less than 4 weeks from study entry)
  • International normalized ratio (INR) =< 1.5 and partial thromboplastin time (PTT) (PTT/activated partial thromboplastin time [aPTT]) < 1.5 x upper limits of normal (ULN) (obtained less than 4 weeks from study entry). Patients receiving warfarin must be switched to low molecular weight heparin and have achieved stable coagulation profile prior to first dose of protocol therapy
  • Total serum bilirubin =< 1.5 x ULN (patients with known Gilbert Syndrome, a total bilirubin =< 3.0 x ULN, with direct bilirubin =< 1.5 x ULN) (obtained less than 4 weeks from study entry)
  • Serum glutamic-oxaloacetic transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT) =< 3 X ULN if no liver metastasis present (obtained less than 4 weeks from study entry)
  • SGOT, SGPT =< 5 X ULN if liver metastasis present (obtained less than 4 weeks from study entry)
  • Human immunodeficiency virus (HIV): stable on antiretroviral therapy (ART) for at least 4 weeks, no documented evidence of multi-drug resistance, viral load of < 400 copies/ml and CD4+ T-cells =< 350 cells/uL (obtained less than 4 weeks from study entry)
  • Hepatitis B virus (HBV)/hepatitis C virus (HCV): participant on a stable dose of antiviral therapy, HBV viral load below the limit of quantification. HCV viral load below the limit of quantification (obtained less than 4 weeks from study entry)
  • Females of childbearing potential must not be breast feeding and must have a negative serum or urine pregnancy test within 7 days of starting of treatment. The patient must agree to use adequate contraception for a minimum of two weeks prior to receiving study medication until 65 days after discontinuation of the study medication. Acceptable methods of contraception include total and true sexual abstinence, hormonal contraceptives that are not prone to drug-drug interactions (IUS levonorgestrel intra uterine system [Mirena], medroxyprogesterone injections [Depo-Provera]), copper-banded intra-uterine devices, and vasectomized partner. All hormonal methods of contraception should be used in combination with the use of a condom by their sexual male partner. Females of childbearing potential are defined as those who are not surgically sterile (i.e., bilateral tubal ligation, bilateral oophorectomy, or complete hysterectomy) or postmenopausal (defined as 12 months with no menses without an alternative medical cause). Women will be considered post-menopausal if they have been amenorrheic for the past 12 months without an alternative medical cause. The following age-specific requirements must also apply: women < 50 years old: they would be considered post-menopausal if they have been amenorrheic for the past 12 months or more following cessation of exogenous hormonal treatments. The levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) must also be in the post-menopausal range (as per the institution). Women >= 50 years old: they would be consider post-menopausal if they have been amenorrheic for the past 12 months or more following cessation of all exogenous hormonal treatments, or have had radiation-induced oophorectomy with the last menses > 1 year ago, or have had chemotherapy-induced menopause with > 1 year interval since last menses, or have had surgical sterilization by either bilateral oophorectomy or hysterectomy
  • Non-sterilized males who are sexually active with a female partner of childbearing potential must use adequate contraception for the duration of the study and 125 days after the last dose of study medication. Adequate contraception methods include: birth control pills (e.g. combined oral contraceptive pill), barrier protection, and abstinence. Patients should not father a child for 125 days after completion of the study medication. Patients should refrain from donating sperm from the start of dosing until 125 days after discontinuing the study medication. If male patients wish to father children they should be advised to arrange for freezing of sperm samples prior to the start of the study medication

Who cannot join

  • Previous treatments with cytotoxic chemotherapy or checkpoint immunotherapy or combination of chemo-immunotherapy for metastatic disease. If the patient had prior chemotherapy as neoadjuvant or adjuvant therapy, the completion of treatment must be greater than 6 months until the beginning of the treatment on trial
  • Previous treatment with any anti-TGF-beta medications
  • Spinal cord compression or brain metastases unless asymptomatic or stable for at least 2 weeks prior to start of study treatment
  • Persisting grade > 1 Common Terminology Criteria for Adverse Events (CTCAE) 5.0 toxicity (except alopecia and vitiligo) related to prior therapy; however, sensory neuropathy grade =< 2 is acceptable
  • Current use of immunosuppressive medication, EXCEPT for the following:
  • Intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection);
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  • Systemic corticosteroids at physiologic doses =< 10 mg/day of prednisone or equivalent;
  • Steroids as premedication for hypersensitivity reactions (e.g., computed tomography [CT] scan premedication).
  • Active autoimmune disease that might deteriorate when receiving an immuno-stimulatory agent. Patients with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment are eligible
  • Any evidence of current interstitial lung disease (ILD) or pneumonitis or a prior history of ILD or non-infectious pneumonitis requiring high-dose glucocorticoids
  • No previous malignant disease within the last 3 years except for a. superficial/non-invasive bladder cancer, or basal or squamous cell carcinoma in situ treated with curative intent; b. endoscopically resected gastrointestinal (GI) cancers limited to the mucosal layer without recurrence in > 1 year
  • No prior organ transplantation including allogenic stem-cell transplantation, except transplants that do not require immunosuppression
  • Active infection requiring systemic therapy
  • Live vaccination that has received or will receive within 30 days prior to the first administration of study intervention. Seasonal flu vaccines that do not contain a live virus are permitted. COVID-19 vaccines are permitted
  • Known severe hypersensitivity (grade >= 3 National Cancer Institute [NCI] CTCAE 5.0) to investigational product or any component in its formulations, any history of anaphylaxis, or recent, within 5 months, history of uncontrollable asthma
  • Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (< 6 months prior to enrollment), myocardial infarction (< 6 months prior to enrollment), unstable angina, congestive heart failure (>= New York Heart Association Classification class II), or serious cardiac arrhythmia requiring medication
  • History of bleeding diathesis or recent major bleeding events (i.e. grade >= 2 bleeding events in the month prior treatment)
  • Males and females of reproductive potential who are not using and effective method of birth control and females who are pregnant or breastfeeding or have a positive (urine or serum) pregnancy test prior to study entry. Females who are pregnant or breast-feeding
  • Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirement

Trial locations and contacts

1 site in 1 country.

United States1 site

  • M D Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: A Single-Arm Phase 2 Study to Investigate Bintrafusp Alfa With Platinum-Pemetrexed for TKI-Resistant EGFR-Mutant NSCLC

This phase II trial studies the effect of bintrafusp alfa with pemetrexed and platinum-based chemotherapy (carboplatin or cisplatin) in treating patients with EGFR mutant non-small cell lung cancer that have spread to nearby tissue or lymph nodes (locally advanced) or other places in the body (metastatic) and cannot be removed by surgery, and remains despite treatment with tyrosine kinase inhibitors (Resistant). Immunotherapy with bintrafusp alfa, a bifunctional fusion protein composed of the monoclonal antibody anti-PD-L1 and TGF-beta, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Pemetrexed may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Chemotherapy drugs, such as carboplatin and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving bintrafusp alfa with pemetrexed and platinum-based chemotherapy may help to control the disease.

Being tested
Bintrafusp Alfa, Pemetrexed, Carboplatin, Cisplatin
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 1918149-01-5, Anti-PDL1/TGFb Trap MSB0011359C, M7824, MSB0011359C

    Given IV

  • PemetrexedDrug

    Also called 137281-23-3, L-Glutamic Acid, N-(4-(2-(2-Amino-4,7-dihydro-4-oxo-1H-pyrrolo(2,3-d)pyrimidin-5-yl)ethyl)benzoyl), MTA

    Given IV

  • CarboplatinDrug

    Also called (SP-4-2)-diammine[1,1-cyclobutanedicarboxylato(2--)-O,O'']platinum, 1-cyclobutanedicarboxylic acid platinum complex, 41575-94-4, Blastocarb

    Given IV

  • CisplatinDrug

    Also called (SP-4-2)-Diamminedichloroplatinum, 15663-27-1, Abiplatin, Blastolem

    Given IV

Study groups in NCT04971187
Study groupRoleWhat they receive
Treatment (bintrafusp alfa, pemetrexed, carboplatin/cisplatin)ExperimentalPatients receive bintrafusp alfa IV over 1 hour on day 1 and pemetrexed IV over 10 minutes on day 1. Patients also receive carboplatin IV over 15 minutes or cisplatin IV over 6-8 hours at the physician's discretion on day 1 of cycles 1-4. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Bintrafusp Alfa; Drug: Pemetrexed; Drug: Carboplatin; Drug: Cisplatin

What is being measured

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

  1. Best Objective Response Rate (ORR) Within 6 Months

    Objective response was assessed by RECIST 1.1. The best overall response is the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started).

    Measured: Within 6 months since initiation of treatment

  2. Progression Free Survival (PFS) at 18 Weeks

    PFS is defined as the date of randomization to the date of disease progression or death due to any cause, whichever occurs earlier as per Response evaluation criteria in solid tumors (RECIST) version 1.1 at 18 weeks.

    Measured: 18 weeks

Secondary outcomes (5)

  1. Safety and Tolerability

    Safety and tolerability as measured by all adverse events (AEs). Safety and tolerability will be described using frequency of AEs and AEs of Common Terminology Criteria for Adverse Events (CTCAE 5.0). Safety analyses will include all patients who have received at least one dose of study drug and will be evaluated descriptively.

    Measured: Up to 30 days post-treatment

  2. Progression Free Survival (PFS)

    PFS is defined as the date of randomization to the date of disease progression or death due to any cause, whichever occurs earlier as per Response evaluation criteria in solid tumors (RECIST) version 1.1.

    Measured: Up to 1 year

  3. Disease Control Rate (DCR)

    DCR was defined as the proportion of patients who had an overall response of complete response (CR), partial response (PR), or stable disease (SD). According to Response Evaluation Criteria In Solid Tumours (RECIST) Version 1.1

    Measured: Up to 1 year

  4. Duration of Response (DoR)

    The duration of overall response is measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started, or death due to any cause. Participants without events reported are censored at the last disease evaluation)

    Measured: Up to 1 year

  5. Overall Survival (OS)

    Overall Survival (OS) is defined as the time from treatment to death due to any cause, or censored at date last known alive.

    Measured: Up to 1 year

Timeline

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

  1. First posted21 Jul 2021
  2. Study start30 Jun 2021
  3. Primary completion21 Feb 2022
  4. Study completion21 Feb 2022

Why it stopped: PI Request

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
3 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04971187
Sponsor's protocol ID
2020-1266
Other IDs
NCI-2021-07070
Status last verified
Jul 2023
First submitted
16 Jul 2021
Last updated
1 Aug 2023
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, Pemetrexed and Carboplatin in people with Locally Advanced Lung Non-Squamous Non-Small Cell Carcinoma and Metastatic Lung Non-Squamous Non-Small Cell Carcinoma, 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 24 inclusion and 19 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 1 Aug 2023. 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 1 Aug 2023). 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?

Best Objective Response Rate (ORR) Within 6 Months (time frame: Within 6 months since initiation of treatment). The study lists 2 primary outcomes in all. 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 NCT04971187.

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 1 Aug 2023.

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