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

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

Status

Terminated

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT04971187

Enrollment

Registered

2021-07-21

Start date

2021-06-30

Completion date

2022-02-21

Last updated

2023-08-01

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Locally Advanced Lung Non-Squamous Non-Small Cell Carcinoma, Metastatic Lung Non-Squamous Non-Small Cell Carcinoma, Stage IIIA Lung Cancer AJCC v8, Stage IIIB Lung Cancer AJCC v8, Stage IIIC Lung Cancer AJCC v8, Stage III Lung Cancer AJCC v8, Stage IVA Lung Cancer AJCC v8, Stage IVB Lung Cancer AJCC v8, Stage IV Lung Cancer AJCC v8, Unresectable Lung Non-Squamous Non-Small Cell Carcinoma

Brief 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 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.

Interventions

DRUGBintrafusp Alfa

Given IV

DRUGPemetrexed

Given IV

DRUGCarboplatin

Given IV

DRUGCisplatin

Given IV

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* 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. * 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

Exclusion criteria

* 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); * 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

Design outcomes

Primary

Measure	Time frame	Description
Best Objective Response Rate (ORR) Within 6 Months	Within 6 months since initiation of treatment	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).
Progression Free Survival (PFS) at 18 Weeks	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.

Secondary

Measure	Time frame	Description
Disease Control Rate (DCR)	Up to 1 year	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
Safety and Tolerability	Up to 30 days post-treatment	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.
Overall Survival (OS)	Up to 1 year	Overall Survival (OS) is defined as the time from treatment to death due to any cause, or censored at date last known alive.
Duration of Response (DoR)	Up to 1 year	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)
Progression Free Survival (PFS)	Up to 1 year	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.

Countries

United States

Participant flow

Pre-assignment details

3 participants were registered, 2 participants were not treated, not eligible or inevaluable, 1 participants received treatment

Participants by arm

Arm	Count
Treatment (Bintrafusp Alfa, Pemetrexed, Carboplatin/Cisplatin) Patients 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.	3
Total	3

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Screen failures	2

Baseline characteristics

Characteristic	Treatment (Bintrafusp Alfa, Pemetrexed, Carboplatin/Cisplatin)
Age, Categorical <=18 years	0 Participants
Age, Categorical >=65 years	1 Participants
Age, Categorical Between 18 and 65 years	2 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	3 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	0 Participants
Race (NIH/OMB) Black or African American	0 Participants
Race (NIH/OMB) More than one race	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) White	3 Participants
Region of Enrollment United States	3 participants
Sex: Female, Male Female	1 Participants
Sex: Female, Male Male	2 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	1 / 1
other Total, other adverse events	0 / 1
serious Total, serious adverse events	1 / 1

Outcome results

Primary

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).

Time frame: Within 6 months since initiation of treatment