| Eligibility |
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
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