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Metastatic Lung Non-Small Cell CarcinomaPhase 1NCT04837716

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

A Phase 1 study testing Bevacizumab, Carboplatin and Ensartinib in people with Metastatic Lung Non-Small Cell Carcinoma and Recurrent Lung Non-Small Cell Carcinoma, run by M.D. Anderson Cancer Center at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Bevacizumab, Carboplatin and Ensartinib
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
12 participants
Where
1 siteUnited States
Study dates
18 Mar 2021to 23 Sep 2027
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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
  • Activated PTT (aPTT) =< 1.5 x ULN unless subject is receiving anticoagulant therapy if PT or PTT is within therapeutic range of intended use of anticoagulant
  • Female patients of childbearing potential must have a negative pregnancy test documented at time of screening
  • Female patients who:
  • Are postmenopausal for at least 1 year before the screening visit, OR
  • Are surgically sterile, OR
  • If they are of childbearing potential, agree to use a highly effective method of contraception from the time of signing the informed consent through 4 months after the last dose of study drug, or agree to completely abstain from heterosexual intercourse
  • Male patients, even if surgically sterilized (i.e., status post-vasectomy), who:
  • Agree to practice effective barrier contraception during the entire study treatment period and through 4 months after the last dose of study drug, or
  • Agree to completely abstain from heterosexual intercourse
  • Voluntary agreement to provide written informed consent and the willingness and ability to comply with all aspects of the protocol

Who cannot join

  • 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:
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  • 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)
  • The following within 6 months prior to cycle 1 day 1:
  • Congestive heart failure (New York Heart class III or IV)
  • Arrhythmia or conduction abnormality requiring medication. Note: patients with atrial fibrillation/flutter controlled by medication and arrhythmias controlled by pacemakers are eligible
  • Severe/unstable angina, coronary artery/peripheral bypass graft, or myocardial infarction
  • Cerebrovascular accident or transient ischemia
  • Patients who are immunosuppressed (including known human immunodeficiency virus [HIV] infection), have a serious active infection at the time of treatment, have interstitial lung disease/pneumonitis, or have any serious underlying medical condition that would impair the ability of the patient to receive protocol treatment. Patients with controlled hepatitis C, in the investigator's opinion, are allowed. Patients with known hepatitis B must be hepatitis B virus e antigen (HBeAg) and HB viral deoxyribonucleic acid (DNA) negative for enrollment. Note that, because of the high prevalence, all patients in the Asia-Pacific region (except Australia, New Zealand, and Japan) must be tested and, if hepatitis B surface antigen (HBsAg) positive, must be HBeAg and HB viral DNA negative for enrollment
  • Known hypersensitivity to tartrazine, a dye used in the ensartinib 100 mg capsule
  • Concurrent condition that in the investigator's opinion would jeopardize compliance with the protocol or would impart excessive risk associated with study participation that would make it inappropriate for the patient to be enrolled
  • Inability or unwillingness to comply with study and/or follow-up procedures outlined in the protocol

Trial locations and contacts

1 site in 1 country.

United States1 site

  • M D Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: A Phase 1b Study of Ensartinib in Combination With Platinum-Based Chemotherapy and Bevacizumab in ALK-Positive Non-Small Cell Lung Cancer (NSCLC)

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the safety of ensartinib in combination with carboplatin, pemetrexed and bevacizumab in patients with ALK-rearranged advanced non-small cell lung cancer (NSCLC).

II. Determine the recommended phase 2 dose (RP2D) of ensartinib in combination with carboplatin, pemetrexed and bevacizumab.

SECONDARY OBJECTIVES:

  1. To determine an objective response rate (ORR) in patients with ALK-rearranged advanced NSCLC treated with ensartinib in combination with carboplatin, pemetrexed and bevacizumab using modified Response Evaluation Criteria in Solid Tumors (RECIST 1.1).

II. To determine progression-free survival (PFS). III. To determine overall survival.

EXPLORATORY OBJECTIVE:

  1. To determine biomarkers associated with response and resistance to the study combination.

OUTLINE: This is a dose de-escalation study of ensartinib and fixed-dose carboplatin, pemetrexed, and bevacizumab followed by a dose-expansion study.

INDUCTION THERAPY: Patients receive ensartinib orally (PO) once daily (QD) on days 1-21, carboplatin intravenously (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.

After completion of study treatment, patients are followed up for 30 days.

Being tested
Bevacizumab, Carboplatin, Ensartinib, Pemetrexed
Medical subject headings
Carcinoma, Non-Small-Cell Lung, Lung Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BevacizumabBiological

    Also called Anti-VEGF, Anti-VEGF Humanized Monoclonal Antibody, Anti-VEGF rhuMAb, Avastin

    Given IV

  • CarboplatinDrug

    Also called Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino

    Given IV

  • EnsartinibDrug

    Also called X-396

    Given PO

  • PemetrexedDrug

    Also called MTA, Multitargeted Antifolate, Pemfexy

    Given IV

Study groups in NCT04837716
Study groupRoleWhat they receive
Treatment (ensartinib, carboplatin, pemetrexed, bevacizumab)ExperimentalINDUCTION 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.
Receives: Biological: Bevacizumab; Drug: Carboplatin; Drug: Ensartinib; Drug: Pemetrexed

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence of adverse events

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

    Measured: Up to 30 days

  2. 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.

    Measured: Up to 21 days

Secondary outcomes (3)

  1. Objective response rate

    Assessed using modified Response Evaluation Criteria in Solid Tumors (1.1). The response rate will be estimated with their exact 95% confidence intervals.

    Measured: Up to 1.5 years

  2. Progression-free survival

    Will be estimated using the method of Kaplan and Meier.

    Measured: Up to 1.5 years

  3. Overall survival

    Will be estimated using the method of Kaplan and Meier.

    Measured: Up to 1.5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Apr 2021
  2. Study start18 Mar 2021
  3. Primary completion23 Sep 2027 (estimated)
  4. Study completion23 Sep 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
12 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04837716
Sponsor's protocol ID
2020-0838
Other IDs
NCI-2021-02560, 2020-0838
Status last verified
Aug 2026
First submitted
5 Apr 2021
Last updated
11 Aug 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Bevacizumab, Carboplatin and Ensartinib in people with Metastatic Lung Non-Small Cell Carcinoma and Recurrent Lung Non-Small Cell Carcinoma, run by M.D. Anderson Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 25 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 11 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of adverse events (time frame: Up to 30 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04837716.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Aug 2026.

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