| Eligibility |
Inclusion Criteria:
- Patient, or patient's authorized representative, must be willing and capable of giving
written informed consent and must be able to adhere to dosing and visit schedules as
well as meet all study requirements
- Patient has histologically or cytologically confirmed non-small cell lung cancer
(NSCLC) not amenable to curative intent therapy or stage IV NSCLC
- Documented epidermal growth factor receptor (EGFR) exon 20 point or insertion
mutation using a Food and Drug Administration (FDA)-approved in vitro diagnostic
test (ie, cobas EGFR mutation test version [v] 2 or therascreen EGFR RGQ
polymerase chain reaction [PCR] kit), a Clinical Laboratory Improvement Act
(CLIA) certified test (eg, OncoMine Comprehensive Assay (OCA), Guardant360 Assay
[using plasma], or FoundationOne Assay), or similarly accredited test for tissue
or plasma
- Brain metastases are allowed, as long as they are stable and do not require
treatment with anticonvulsants or escalating doses of steroids
- Previously untreated and/or any number of prior lines of therapy for metastatic
disease are allowed in the dose expansion part. Previously untreated patients are
now allowed in the dose finding portion of the study
- Patient is at least 18 years of age
- Patient has measurable disease, as per the Response Evaluation Criteria in Solid
Tumors (RECIST, version 1.1)
- Patient has an Eastern Cooperative Oncology Group (ECOG) performance status 0 or
1
- Patient has recovered from prior systemic therapy for metastatic disease to grade
=< 1 for non-hematologic toxicities (except for grade =< 2 peripheral neuropathy)
- Leukocytes >= 3.0 x 10^9/L
- Absolute neutrophil count (ANC) must be >= 1.5 x 10^9/L
- Platelet count >= 100 x 10^9/L
- Hemoglobin >= 9.0 g/dL
- Total bilirubin =<1.5 x upper limit of normal (ULN); if hepatic metastases are
present, =< 2.5 x ULN
- Aspartate aminotransferase/serum glutamic-oxaloacetic transaminase (AST/SGOT),
alanine aminotransferase/serum glutamic-pyruvic transaminase (ALT/SGPT), and
gamma-glutamyltransferase (GGT) =< 2.5 x ULN; if hepatic metastases are present,
=< 0.5 x ULN
- Creatinine clearance >= 50 mL/min
- Adequate coagulation function as defined by international normalized ratio (INR)
1.5 and a partial thromboplastin time (PTT) (PTT/activated partial thromboplastin
time [aPTT]) < 1.5 x ULN. Patients on full-dose anticoagulation must be on a
stable dose (minimum duration 14 days) of oral anticoagulant or low molecular
weight heparin (LMWH). If receiving warfarin, the patient must have an INR =<
3.0. For heparin and LMWH there should be no active bleeding (that is, no
bleeding within 14 days prior to first dose of protocol therapy) or pathological
condition present that carries a high risk of bleeding (for example, tumor
involving major vessels or known varices)
- Patient is willing to practice 2 forms of contraception, one of which must be a
barrier method, from study entry until at least 30 days after the last dose of
study combination
- Females of childbearing potential must have a negative pregnancy test within 7
days prior to enrollment. Females who are postmenopausal for at least 1 year
(defined as more than 12 months since last menses) or who are surgically
sterilized do not require this test
- The patient's urinary protein is =< 1+ on dipstick or routine urinalysis (UA; if
urine dipstick or routine analysis is >= 2+, a 24-hour urine collection for
protein must demonstrate < 1000 mg of protein in 24 hours to allow participation
in this protocol)
Exclusion Criteria:
- • Patient has EGFR T790M mutation or other acquired EGFR exon 20point mutation
following prior treatment with an EGFR-tyrosine kinase inhibitor (TKI)
- Previous treatment with poziotinib or ramucirumab
- Patient is concurrently receiving chemotherapy, biologics, immunotherapy for
cancer treatment; systemic anti-cancer treatment or investigational treatment
should not be used within 2 weeks; local radiation therapy for bone pain may be
allowed
- Patient has a history of congestive heart failure (CHF) class III/IV according to
the New York Heart Association (NYHA) functional classification or serious
cardiac arrhythmias requiring treatment
- Patient has a high risk of cardiac disease, as determined by the investigator,
may undergo either echocardiogram (ECHO) or multi-gated acquisition (MUGA) during
screening and if the patient has a cardiac ejection fraction < 50%, the patient
will be excluded
- Patient has a history of other malignancies within the last 3 years, except for
non-melanoma skin cancer or carcinoma in situ of the cervix
- Patient is confirmed to have clinically significant or recent (within 14 days
prior to starting treatment) acute gastrointestinal disease presenting as
diarrhea and/or coloenteritis as a main symptom (ie, acute enteritis,
malabsorption, or Common Terminology Criteria for Adverse Events [CTCAE, version
5.0] grade 2 or above diarrhea due to other etiologies)
- Patient is unable to take drugs orally due to disorders or diseases that may
affect gastrointestinal (GI) function, such as inflammatory bowel diseases (eg,
Crohn's disease, ulcerative colitis) or malabsorption syndrome, or procedures
that may affect gastrointestinal function, such as gastrectomy, enterectomy, or
colectomy
- Patient has an active liver disease or biliary tract disease (except for
Gilbert's disease, asymptomatic biliary stones, liver metastasis, or stabilized
chronic liver diseases). Patients with liver cirrhosis at a level of Child-Pugh B
(or worse) or history of hepatic encephalopathy or clinically meaningful ascites
resulting from cirrhosis are excluded.
- Patient has known hypersensitivity to poziotinib or ramucirumab
- Patient has an active uncontrolled infection, underlying medical condition, or
other serious illness that would impair the ability of the patient to receive
protocol treatment
- Patient has experienced any grade 3-4 GI bleeding within 3 months prior to first
dose of protocol therapy.
- Patient has a history of deep vein thrombosis (DVT), pulmonary embolism (PE), or
any other significant thromboembolism (venous port or catheter thrombosis or
superficial venous thrombosis are not considered "significant") during the 3
months prior to first dose of protocol therapy
- The patient has experienced any arterial thromboembolic events, including but not
limited to myocardial infarction, transient ischemic attack, cerebrovascular
accident, or unstable angina, within 6 months prior to first dose of protocol
therapy
- The patient has uncontrolled or poorly-controlled hypertension (> 160 mmHg
systolic or > 100 mmHg diastolic for > 4 weeks) despite standard medical
management
- If they experience hemoptysis (defined as bright red blood or >= 1/2 teaspoon)
within 2 months prior to first dose of protocol therapy or with radiographic
evidence of intratumor cavitation or has radiologically documented evidence of
major blood vessel invasion or encasement by cancer
- Patient has had recent major surgery within 28 days prior to starting study
treatment, or minor surgery/subcutaneous venous access device placement within 7
days prior to the first dose of protocol therapy. The patient has elective or
planned major surgery to be performed during the course of the clinical trial.
- The patient has a prior history of GI perforation/fistula (within 6 months of
first dose of protocol therapy) or risk factors for perforation
- The patient has a serious or nonhealing wound, ulcer, or bone fracture within 28
days prior to first dose of protocol therapy
- Patient has EGFR T790M mutation or other acquired EGFR exon 20point mutation
following prior treatment with an EGFR-tyrosine kinase inhibitor (TKI)
- Previous treatment with poziotinib or ramucirumab
- Patient is concurrently receiving chemotherapy, biologics, immunotherapy for
cancer treatment; systemic anti-cancer treatment or investigational treatment
should not be used within 2 weeks; local radiation therapy for bone pain may be
allowed
- Patient has a history of congestive heart failure (CHF) class III/IV according to
the New York Heart Association (NYHA) functional classification or serious
cardiac arrhythmias requiring treatment
- Patient has a high risk of cardiac disease, as determined by the investigator,
may undergo either echocardiogram (ECHO) or multi-gated acquisition (MUGA) during
screening and if the patient has a cardiac ejection fraction < 50%, the patient
will be excluded
- Patient has a history of other malignancies within the last 3 years, except for
non-melanoma skin cancer or carcinoma in situ of the cervix
- Patient is confirmed to have clinically significant or recent (within 14 days
prior to starting treatment) acute gastrointestinal disease presenting as
diarrhea and/or coloenteritis as a main symptom (ie, acute enteritis,
malabsorption, or Common Terminology Criteria for Adverse Events [CTCAE, version
5.0] grade 2 or above diarrhea due to other etiologies)
- Patient is unable to take drugs orally due to disorders or diseases that may
affect gastrointestinal (GI) function, such as inflammatory bowel diseases (eg,
Crohn's disease, ulcerative colitis) or malabsorption syndrome, or procedures
that may affect gastrointestinal function, such as gastrectomy, enterectomy, or
colectomy
- Patient has an active liver disease or biliary tract disease (except for
Gilbert's disease, asymptomatic biliary stones, liver metastasis, or stabilized
chronic liver diseases). Patients with liver cirrhosis at a level of Child-Pugh B
(or worse) or history of hepatic encephalopathy or clinically meaningful ascites
resulting from cirrhosis are excluded.
- Patient has known hypersensitivity to poziotinib or ramucirumab
- Patient has an active uncontrolled infection, underlying medical condition, or
other serious illness that would impair the ability of the patient to receive
protocol treatment
- Patient has experienced any grade 3-4 GI bleeding within 3 months prior to first
dose of protocol therapy.
- Patient has a history of deep vein thrombosis (DVT), pulmonary embolism (PE), or
any other significant thromboembolism (venous port or catheter thrombosis or
superficial venous thrombosis are not considered "significant") during the 3
months prior to first dose of protocol therapy
- The patient has experienced any arterial thromboembolic events, including but not
limited to myocardial infarction, transient ischemic attack, cerebrovascular
accident, or unstable angina, within 6 months prior to first dose of protocol
therapy
- The patient has uncontrolled or poorly-controlled hypertension (> 160 mmHg
systolic or > 100 mmHg diastolic for > 4 weeks) despite standard medical
management
- If they experience hemoptysis (defined as bright red blood or >= 1/2 teaspoon)
within 2 months prior to first dose of protocol therapy or with radiographic
evidence of intratumor cavitation or has radiologically documented evidence of
major blood vessel invasion or encasement by cancer
- Patient has had recent major surgery within 28 days prior to starting study
treatment, or minor surgery/subcutaneous venous access device placement within 7
days prior to the first dose of protocol therapy. The patient has elective or
planned major surgery to be performed during the course of the clinical trial.
- The patient has a prior history of GI perforation/fistula (within 6 months of
first dose of protocol therapy) or risk factors for perforation
- The patient has a serious or nonhealing wound, ulcer, or bone fracture within 28
days prior to first dose of protocol therapy
- Patient is pregnant or breast-feeding
- The patient is receiving chronic antiplatelet therapy, including dipyridamole or
clopidogrel, or similar agents. Once-daily aspirin use (maximum dose 325 mg/day)
is permitted
- The presence of interstitial lung disease, drug-related pneumonitis, or radiation
pneumonitis at screening
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