Ensartinib, Carboplatin, Pemetrexed and Bevacizumab for the Treatment of Stage IIIC or IV or Recurrent ALK-Positive Non-small Cell Lung Cancer

NCT04837716 | Active Not Recruiting Phase 1 FDA Drug

• 2 other identifiers: 2020-0838NCI-2021-02560
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

This phase Ib trial finds the best dose and side effects of ensartinib and its effects when given with carboplatin, pemetrexed and bevacizumab for in treating patients with ALK-positive non-small cell lung cancer that is stage IIIC or IV, or has come back (recurrent). Ensartinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Chemotherapy drugs, such as carboplatin and pemetrexed, 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. Bevacizumab is a monoclonal antibody that may interfere with the ability of tumor cells to grow and spread. Giving ensartinib, carboplatin, pemetrexed and bevacizumab may help to control the disease.

Conditions

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

Outcome Measures

Primary Outcomes (2)

• Incidence of adverse events

  The toxicity rate will be estimated with their exact 95% confidence intervals.

  Up to 30 days

• Recommended phase 2 dose

  Will employ the Bayesian optimal interval (BOIN) design (Liu and Yuan, 2015; Yuan et al., 2016) to find the maximum tolerated dose of ensartinib in combination with carboplatin, pemetrexed and bevacizumab.

  Up to 21 days

Secondary Outcomes (3)

• Objective response rate

  Up to 1.5 years

• Progression-free survival

  Up to 1.5 years

• Overall survival

  Up to 1.5 years

Other Outcomes (1)

• Biomarkers associated with response and resistance

  Up to 1.5 years

Study Arms (1)

Treatment (ensartinib, carboplatin, pemetrexed, bevacizumab)

EXPERIMENTAL

INDUCTION THERAPY: Patients receive ensartinib PO QD on days 1-21, carboplatin IV over 15-60 minutes on day 1, pemetrexed IV over 10 minutes on day 1 and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Patients receive ensartinib PO QD on days 1-21 and bevacizumab IV over 30-90 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Biological: Bevacizumab; Drug: Carboplatin; Drug: Ensartinib; Drug: Pemetrexed

Interventions

Bevacizumab BIOLOGICAL

Given IV

Also known as: Anti-VEGF, Anti-VEGF Humanized Monoclonal Antibody, Anti-VEGF rhuMAb, Avastin, Bevacizumab awwb, Bevacizumab Biosimilar BEVZ92, Bevacizumab Biosimilar BI 695502, Bevacizumab Biosimilar CBT 124, Bevacizumab Biosimilar CT-P16, Bevacizumab Biosimilar FKB238, Bevacizumab Biosimilar GB-222, Bevacizumab Biosimilar HD204, Bevacizumab Biosimilar HLX04, Bevacizumab Biosimilar IBI305, Bevacizumab Biosimilar LY01008, Bevacizumab Biosimilar MIL60, Bevacizumab Biosimilar Mvasi, Bevacizumab Biosimilar QL 1101, Bevacizumab Biosimilar RPH-001, Bevacizumab Biosimilar SCT501, Bevacizumab Biosimilar Zirabev, Bevacizumab-awwb, Bevacizumab-bvzr, BP102, BP102 Biosimilar, HD204, Immunoglobulin G1 (Human-Mouse Monoclonal rhuMab-VEGF Gamma-Chain Anti-Human Vascular Endothelial Growth Factor), Disulfide With Human-Mouse Monoclonal rhuMab-VEGF Light Chain, Dimer, Mvasi, Recombinant Humanized Anti-VEGF Monoclonal Antibody, rhuMab-VEGF, SCT501, Zirabev

Treatment (ensartinib, carboplatin, pemetrexed, bevacizumab)

Carboplatin DRUG

Given IV

Also known as: Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino, Carboplatinum, Carbosin, Carbosol, Carbotec, CBDCA, Displata, Ercar, JM-8, Nealorin, Novoplatinum, Paraplatin, Paraplatin AQ, Paraplatine, Platinwas, Ribocarbo

Treatment (ensartinib, carboplatin, pemetrexed, bevacizumab)

Ensartinib DRUG

Given PO

Also known as: X-396

Treatment (ensartinib, carboplatin, pemetrexed, bevacizumab)

Pemetrexed DRUG

Given IV

Also known as: MTA, Multitargeted Antifolate, Pemfexy

Treatment (ensartinib, carboplatin, pemetrexed, bevacizumab)

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically confirmed diagnosis of stage IV (metastatic) or recurrent or stage IIIc NSCLC (recurrent or stage IIIC NSCLC must be not a candidate for definitive multimodality therapy)
• Documented ALK re-arrangement as detected by: (1) fluorescence in situ hybridization (FISH), (2) immunohistochemistry (IHC), (3) tissue next generation sequencing (NGS), or (4) cell free deoxyribonucleic acid (cfDNA) NGS using Clinical Laboratory Improvement Amendments (CLIA) certified laboratory
• Subjects can be enrolled as (1) treatment naive (2) after progression on any number of prior ALK tyrosine kinase inhibitors (TKIs). Prior adjuvant platinum-based chemotherapy and platinum-based chemotherapy for metastatic disease is allowed if completed \> 12 months from the study treatment start date with one exception: a patient may be eligible if started on chemotherapy while waiting for ALK testing results, provided no more than two cycles of chemotherapy were administered and no evidence of disease progression
• Life expectancy of at least 12 weeks
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
• Aged at least 18 years
• Brain metastases allowed if asymptomatic at study baseline. Patients must be not on steroids, with the maximum size of brain lesion not exceeding 30 millimeters. If patients have neurological symptoms or signs due to central nervous system (CNS) metastases, patients need to complete whole brain radiation or focal treatment at least 14 days before start of study treatment and be asymptomatic on stable or decreasing doses of corticosteroids at baseline
• Ability to swallow and retain oral medications
• Absolute neutrophil count (ANC) \>= 1500/mm\^3 /L
• Platelet count \>= 100,000/mm\^3
• Hemoglobin (Hb) at least 9 g/dL (or 5.69 mmol/L) at baseline
• Serum creatinine =\< 1.5 x upper limit of normal (ULN) or creatinine clearance (CrCl) \>= 60 mL/minute for subjects with creatinine levels \> 1.5 x the institutional ULN
• Serum total bilirubin less than or equal to =\< 1.5 x ULN or direct bilirubin =\< ULN for subjects with total bilirubin levels \> 1.5 x ULN
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =\< 2.5 x ULN except for subjects with liver metastases (mets) for whom ALT and AST should be =\< 5 x ULN
• International normalized ratio (INR) or prothrombin time (PT) =\< 1.5 x ULN unless subject is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants

You may not qualify if:

• Use of an investigational drug within 21 days prior to the first dose of study drug. Note that to be eligible, any drug-related toxicity should have recovered to grade 2 or less, with the exception of alopecia
• Major surgery within the last 4 weeks or radiotherapy within the last 14 days
• Patients with leptomeningeal disease are ineligible
• Patients with a previous malignancy within the past 2 years (other than curatively treated basal cell carcinoma of the skin, in situ carcinoma of the cervix, or any cancer that is considered to be cured and have no impact on PFS and overall survival \[OS\] for the current NSCLC)
• Concomitant systemic use of anticancer herbal medications. These should be stopped prior to study entry
• Patients receiving:
• Strong CYP3A inhibitors (including, but not limited to, atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole, grapefruit, grapefruit juice)
• Strong CYP3A inducers (including, but not limited to, carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, St. John's wort)
• CYP3A substrates with narrow therapeutic window (including, but not limited to, alfentanil, cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, tacrolimus)
• Women who are pregnant or breastfeeding
• Presence of active gastrointestinal (GI) disease or other condition that will interfere significantly with the absorption, distribution, metabolism, or excretion of study medications
• Patients at risk for GI perforation
• Clinically significant cardiovascular disease including:
• Corrected QT per Fridericia's formula (QTcF) interval \> 450 ms for men and \> 470 ms for women, symptomatic bradycardia \< 45 beats per minute or other significant electrocardiogram (ECG) abnormalities in the investigator's opinion
• Clinically uncontrolled hypertension in the investigator's opinion (e.g., blood pressure \> 160/100 mmHg; note that isolated elevated readings considered to not be indicative of uncontrolled hypertension are allowed)

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• MD Anderson Cancer Center

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms

Interventions

Bevacizumab; Immunoglobulin G; Disulfides; Carboplatin; ensartinib; Pemetrexed

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Immunoglobulin Isotypes; Sulfides; Anions; Ions; Electrolytes; Inorganic Chemicals; Hydrogen Sulfide; Sulfur Compounds; Organic Chemicals; Coordination Complexes; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Dicarboxylic

Study Officials

• Yasir Y Elamin, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 5, 2021
• First Posted: April 8, 2021
• Study Start: March 18, 2021
• Primary Completion (Estimated): September 23, 2027
• Study Completion (Estimated): September 23, 2027
• Last Updated: February 19, 2026

Record last verified: 2026-02

Locations

US (1)