Poziotinib and Ramucirumab for the Treatment of EGFR Exon 20 Mutant Stage IV Non-small Cell Lung Cancer

NCT05045404 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: 2021-0293
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This phase II trial tests whether poziotinib and ramucirumab work to shrink tumors in patients with EGFR Exon 20 gene mutant stage IV non-small cell lung cancer. Poziotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Ramucirumab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Giving poziotinib and ramucirumab may help to control the disease.

Conditions

Metastatic Lung Non-Small Cell Carcinoma; Stage IV Lung Cancer AJCC v8; Stage IVA Lung Cancer AJCC v8; Stage IVB Lung Cancer AJCC v8

Outcome Measures

Primary Outcomes (1)

• Progression-free survival

  Estimated using the Kaplan and Meier method.

  From start of treatment to time of progression or death, whichever occurs first, assessed up to 3 years

Study Arms (1)

Treatment (poziotinib hydrochloride, ramucirumab)

EXPERIMENTAL

Patients receive poziotinib hydrochloride PO BID on day 1 and ramucirumab IV over 30-60 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Poziotinib Hydrochloride; Biological: 1429757-68-5, HM781-36B, NOV-1201 Hydrochloride, NOV120101 Hydrochloride, Poziotinib HCl, POZIOTINIB HYDROCHLORIDE

Interventions

Poziotinib Hydrochloride DRUG

1429757-68-5, HM781-36B, NOV-1201 Hydrochloride, NOV120101 Hydrochloride, Poziotinib HCl, POZIOTINIB HYDROCHLORIDE Given PO

Treatment (poziotinib hydrochloride, ramucirumab)

1429757-68-5, HM781-36B, NOV-1201 Hydrochloride, NOV120101 Hydrochloride, Poziotinib HCl, POZIOTINIB HYDROCHLORIDE BIOLOGICAL

Biological/Vaccine Ramucirumab 947687-13-0, anti-VEGFR-2 fully human monoclonal antibody IMC-1121B, Anti-VEGFR-2 Fully Human Monoclonal Antibody IMC-1121B, Cyramza, IMC-1121B, IMC-1121B, LY3009806, Monoclonal Antibody HGS-ETR2, ramucirumab, RAMUCIRUMAB Given IV

Treatment (poziotinib hydrochloride, ramucirumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Related Links

• MD Anderson Cancer Center Website

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms

Interventions

HM781-36B

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Yasir Elamin, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 7, 2021
• First Posted: September 16, 2021
• Study Start: June 16, 2021
• Primary Completion: February 2, 2023
• Study Completion: February 2, 2023
• Last Updated: September 13, 2023

Record last verified: 2023-09