AzTrials
AzTrials

Non-small Cell Lung CancerPhase 2NAUTIKA1NCT04302025

A Study of Multiple Therapies in Biomarker-selected Participants With Resectable Stages IB-III Non-small Cell Lung Cancer (NSCLC)

A Phase 2 study testing Alectinib, Entrectinib and Vemurafenib in people with Non-small Cell Lung Cancer, run by Genentech, Inc. at 38 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

This trial will evaluate the efficacy and safety of various therapies in participants with Stage IB, IIA, IIB, IIIA, or selected IIIB resectable and untreated NSCLC tumors that meet protocol-specified biomarker criteria. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Non-small Cell Lung Cancer
What is being tested?
Alectinib, Entrectinib and Vemurafenib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
99 participants
Where
38 sitesUnited States
Study dates
6 Nov 2020to 30 May 2030
Phase
Phase 2
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

  • Pathologically documented NSCLC:
  • Newly diagnosed early-stage NSCLC stages IB, IIA, IIB, IIIA, or selected IIIB (T3N2 only) NSCLC of squamous or non-squamous histology. Staging should be based on the 8th edition of the American Joint Committee on Cancer (AJCC)/Union Internationale Contre le Cancer (UICC) NSCLC staging system
  • T4 primary NSCLC will be allowed only on the basis of size. Invasion of the diaphragm, mediastinum, heart, great vessels, trachea, recurrent laryngeal nerve, esophagus, vertebral body, carina, and separate tumor nodules in a different ipsilateral lobe is not permitted
  • All participants will undergo clinical staging using computed tomography (CT) and positron emission tomography (PET) scanning, as well as brain imaging using magnetic resonance imaging (MRI). Invasive mediastinal staging by either mediastinoscopy or endo-bronchial ultrasonography is highly encouraged for participants with radiographically suspected mediastinal nodal disease (i.e., N2) but not mandated if the CT or PET scans showed no evidence of N2 disease
  • Molecular testing results from clinical laboratory improvement amendments (CLIA)-certified laboratories and showing at least one of the following abnormalities: ALK fusion, ROS1 fusion, NTRK1/2/3 fusion; BRAF V600 mutation, RET fusion, PD-L1 expression in ≥ 1% tumor cells as determined by Food and Drug Administration (FDA)-approved test, KRAS G12C mutation
  • Measurable disease, as defined by RECIST v1.1
Show all 21Show fewer
  • NSCLC must have a solid or subsolid appearance on CT scan and cannot have a purely ground glass opacity appearance. For subsolid lesions, the tumor size (i.e., clinical T stage) should be measured based on the solid component only, exclusive of the ground glass opacity component
  • Evaluated by the attending surgeon prior to study enrollment to verify that the primary tumor and any involved lymph nodes are technically completely resectable and verify that the participant is medically operable
  • Adequate pulmonary function to be eligible for surgical resection with curative intent
  • Adequate cardiac function to be eligible for surgical resection with curative intent
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
  • Adequate hematologic and end-organ function
  • Negative hepatitis B surface antigen (HBsAg) test at screening for cohort
  • Negative total hepatitits B core antibody (HBcAb) test at screening for cohort, or positive total HBcAb test followed by a negative hepatitis B virus (HBV) deoxyribonucleic acid (DNA) test at screening
  • Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV ribonucleic acid (RNA) test at screening
  • Male participants must be willing to use acceptable methods of contraception
  • Female participants of childbearing potential must agree to use acceptable methods of contraception
  • Inclusion Criteria for Adjuvant Therapy (TKI Cohorts and KRAS G12C cohort [if continuing on Divarasib]):
  • Participants whose tumors lack radiographic progression
  • ECOG Performance Status of 0 or 1
  • Adequate hematologic and end-organ function

Who cannot join

  • NSCLC that is clinically T4 by virtue of mediastinal organ invasion or Stage IIIB by virtue of N3 disease
  • Any prior therapy for lung cancer, including chemotherapy, targeted therapy, immunotherapy, or radiotherapy, within 2 years
  • Participants with prior lung cancer
  • Major surgical procedure within 28 days prior to Cycle 1, Day 1
  • Malignancies other than the disease under study within 3 years prior to Cycle 1, Day 1, with the exception of participants with a negligible risk of metastasis or death and with expected curative outcome
  • Treatment with an investigational agent for any condition within 4 weeks prior to Cycle 1, Day 1
Show all 9Show fewer
  • Participants known to be positive for human immunodeficiency virus (HIV) are excluded if they meet any of the following criteria: cluster of differentiation 4 (CD4)+ T-cell count of <350 cells/microliters (cells/µL); detectable HIV viral load; history of an opportunistic infection within the past 12 months; on stable antiretroviral therapy for <4 weeks
  • Severe infection within 4 weeks prior to initiation of study treatment, including but not limited to hospitalization for complications of infections, or any active infection that, in the opinion of the investigator, could impact participant safety
  • Pregnant or lactating, or intending to become pregnant during the study

Trial locations and contacts

38 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Reference Study ID Number: ML41591 https://forpatients.roche.com/ No attachments to email below. contact

888-662-6728

global-roche-genentech-trials@gene.com

Fastest response: use the inquiry form. https://www.gene.com/contact-us/submit-medical-inquiry contact

38 sites in 1 country

United States38 sites, 23 recruiting

  • University of Michigan

    Ann Arbor, Michigan, 48109

    Recruiting

  • University of Colorado - Anschutz Medical Campus (University of Colorado Health Sciences Center)

    Aurora, Colorado, 80045

    Withdrawn

  • Boston Medical Center

    Boston, Massachusetts, 02118

    Withdrawn

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

    Recruiting

  • Northwestern University

    Chicago, Illinois, 60611

    Recruiting

  • University Hospitals Cleveland Medical Center

    Cleveland, Ohio, 44016

    Withdrawn

  • Ellis Fischel Cancer Center

    Columbia, Missouri, 65201

    Recruiting

  • Ohio State University

    Columbus, Ohio, 43210

    Recruiting

  • Northwestern Medicine Cancer Center Kishwaukee

    DeKalb, Illinois, 60115

    Recruiting

  • City of Hope Comprehensive Cancer Center

    Duarte, California, 91010

    Withdrawn

  • Virginia Cancer Specialists (Fairfax) - USOR

    Fairfax, Virginia, 22031

    Recruiting

  • Karmanos Cancer Institute - Farmington Hills/Weisberg Cancer Treatment Center

    Farmington Hills, Michigan, 48334

    Withdrawn

  • Northwestern Medicine Cancer Center Delnor

    Geneva, Illinois, 60134

    Recruiting

  • Kelsey Seybold Clnic

    Houston, Texas, 77025

    Withdrawn

  • University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030-4008

    Recruiting

  • Baylor College of Medicine

    Houston, Texas, 77030

    Withdrawn

  • City of Hope - Orange County Lennar Foundation Cancer Center

    Irvine, California, 92618

    Withdrawn

  • Lumi Research

    Kingwood, Texas, 77339

    Withdrawn

  • Dartmouth Hitchcock Medical Center

    Lebanon, New Hampshire, 03756

    Recruiting

  • USC Norris Cancer Center

    Los Angeles, California, 90033

    Withdrawn

  • Cedars-Sinai Medical Center

    Los Angeles, California, 90048

    Withdrawn

  • University of California Los Angeles - Jonsson Comprehensive Cancer Center

    Los Angeles, California, 90095

    Recruiting

  • Baptist Clinical Research Institute

    Memphis, Tennessee, 38120

    Recruiting

  • Tennessee Oncology - Nashville

    Nashville, Tennessee, 37203

    Withdrawn

  • Yale Cancer Center

    New Haven, Connecticut, 06511

    Recruiting

  • Laura and ISAAC Perlmutter Cancer Center at NYU Langone.

    New York, New York, 10016

    Recruiting

  • Columbia University Medical Center

    New York, New York, 10032

    Recruiting

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

    Recruiting

  • The Center for Cancer Prevention and Treatment at St.Joseph Hospital of Orange

    Orange, California, 92868

    Recruiting

  • AHN Cancer Institute ? Allegheny General Hospital

    Pittsburgh, Pennsylvania, 15212

    Completed

  • Mayo Clinic

    Rochester, Minnesota, 55905

    Recruiting

  • UC Davis Comprehensive Cancer Center

    Sacramento, California, 95817

    Recruiting

  • UCSF Helen Diller Family CCC

    San Francisco, California, 94158

    Withdrawn

  • Seattle Cancer Care Alliance

    Seattle, Washington, 98109

    Withdrawn

  • Siteman Cancer Center - Washington University Medical Campus

    St Louis, Missouri, 63108

    Recruiting

  • Moffitt Cancer Center

    Tampa, Florida, 33612

    Recruiting

  • Northwestern Medicine Cancer Center Warrenville

    Warrenville, Illinois, 60555

    Recruiting

  • MedStar Georgetown University Hospital (Lombardi Comprehensive Cancer Center)

    Washington D.C., District of Columbia, 20007

    Recruiting

Other trials in United States

About this study

Official title: NAUTIKA1: A Multicenter, Phase II, Neoadjuvant and Adjuvant Study of Multiple Therapies in Biomarker-selected Patients With Resectable Stages IB-III Non-small Cell Lung Cancer

This trial will evaluate the efficacy and safety of various therapies in participants with Stage IB, IIA, IIB, IIIA, or selected IIIB resectable and untreated NSCLC tumors that meet protocol-specified biomarker criteria.

Being tested
Alectinib, Entrectinib, Vemurafenib, Cobimetinib, Pralsetinib
Medical subject headings
Carcinoma, Non-Small-Cell Lung

What participants receive

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

  • AlectinibDrug

    Also called CH5424802; RO5424802

    Participants will receive oral alectinib twice per day (BID).

  • EntrectinibDrug

    Also called Rozlytrek®; RXDX-101

    Participants will receive oral entrectinib daily.

  • VemurafenibDrug

    Also called Zelboraf®

    Participants will receive oral vemurafenib BID.

  • CobimetinibDrug

    Also called Cotellic®

    Participants will receive oral cobimetinib daily.

  • PralsetinibDrug

    Also called Gavreto®

    Participants will receive oral pralsetinib daily.

  • AtezolizumabDrug

    Also called Tecentriq®

    Atezolizumab will be administered by intravenous (IV) infusion.

  • SBRTDrug

    Participants will receive SBRT given concurrently, starting with the first dose of atezolizumab.

  • ResectionProcedure or surgery

    Participants will receive surgical resection of the primary tumor along with selected lymph nodes per SOC.

  • ChemotherapyDrug

    Participants will receive SOC chemotherapy as determined by the treating physician.

  • DivarasibDrug

    Also called GDC-6036

    Participants in the KRAS G12C cohort will receive oral divarasib for approximately 8 weeks until the day before surgery as neoadjuvant therapy up to 3 years as adjuvant therapy.

Study groups in NCT04302025
Study groupRoleWhat they receive
ALK Cohort (Enrolment Closed)ExperimentalParticipants will receive up to 8 weeks of alectinib neoadjuvant treatment before undergoing surgical resection per standard of care (SOC). All participants that undergo surgical resection and whose tumors have pathological response or lack radiographic progression will be eligible for the adjuvant treatment phase with alectinib. Adjuvant therapy will consist of 4 cycles of chemotherapy followed by up to 2 years of alectinib. Enrolment Closed.
Receives: Drug: Alectinib; Procedure: Resection; Drug: Chemotherapy
ROS 1 Cohort (Enrolment Closed)ExperimentalParticipants will receive up to 8 weeks of entrectinib neoadjuvant treatment before undergoing surgical resection per SOC. All participants that undergo surgical resection and whose tumors have pathological response or lack radiographic progression will be eligible for the adjuvant treatment phase with entrectinib. Adjuvant therapy will consist of 4 cycles of chemotherapy followed by up to 2 years of entrectinib. Enrolment Closed.
Receives: Drug: Entrectinib; Procedure: Resection; Drug: Chemotherapy
NTRK Cohort (Enrolment Closed)ExperimentalParticipants will receive up to 8 weeks of entrectinib neoadjuvant treatment before undergoing surgical resection per SOC. All participants that undergo surgical resection and whose tumors have pathological response or lack radiographic progression will be eligible for the adjuvant treatment phase with entrectinib. Adjuvant therapy will consist of 4 cycles of chemotherapy followed by up to 2 years of entrectinib. Enrolment Closed.
Receives: Drug: Entrectinib; Procedure: Resection; Drug: Chemotherapy
BRAF Cohort (No Participants Enrolled, Cohort Closed)ExperimentalParticipants will receive up to 8 weeks of vemurafenib plus cobimetinib neoadjuvant treatment before undergoing surgical resection per SOC. All participants that undergo surgical resection and whose tumors have pathological response or lack radiographic progression will be eligible for the adjuvant treatment phase with vemurafenib plus cobimetinib. Adjuvant therapy will consist of 4 cycles of chemotherapy followed by up to 2 years of of vemurafenib plus cobimetinib. Cohort closed.
Receives: Drug: Vemurafenib; Drug: Cobimetinib; Procedure: Resection; Drug: Chemotherapy
RET Cohort (Cohort closed)ExperimentalParticipants will receive up to 8 weeks of pralsetinib neoadjuvant treatment before undergoing surgical resection per SOC. All participants that undergo surgical resection and whose tumors have pathological response or lack radiographic progression will be eligible for the adjuvant treatment phase with pralsetinib. Adjuvant therapy will consist of 4 cycles of chemotherapy followed by up to 2 years of pralsetinib. Cohort closed.
Receives: Drug: Pralsetinib; Procedure: Resection; Drug: Chemotherapy
PD-L1 Cohort (Enrolment Closed)ExperimentalParticipants with positive programmed death-ligand 1 (PD-L1) in ≥1% tumor cells will receive 4 cycles of atezolizumab neoadjuvant treatment. During neoadjuvant Cycle 1 of atezolizumab, participants will also receive low-dose stereotactic body radiation therapy (SBRT) (8 gray [Gy] X 3). Adjuvant treatment consists of SOC treatment as determined by the investigator, per National Comprehensive Cancer Network (NCCN) guidelines. Enrolment Closed.
Receives: Drug: Atezolizumab; Drug: SBRT; Procedure: Resection
KRAS G12C CohortExperimentalParticipants will receive up to 8 weeks of divarasib as neoadjuvant treatment before undergoing surgical resection per SOC. PD-L1 negative participants whose tumors have pathological response or lack radiographic progression will be have the option of continuing divarasib alone for up to 3 years or 1-4 cycles of SOC chemotherapy followed by divarasib for 3 years as adjuvant therapy. For participants who test positive PD-L1, they will have the option to receive 1-4 cycles of SOC chemotherapy followed by atezolizumab for up to 16 cycles or SOC alone.
Receives: Procedure: Resection; Drug: Chemotherapy; Drug: Divarasib

What is being measured

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

  1. Tyrosine Kinase Inhibitor (TKI) Cohort: Proportion of Participants With Major Pathologic Response (MPR)

    MPR is defined as ≤ 10% residual viable tumor cells as scored by local pathologists.

    Measured: After surgical resection (approximately study Week 8)

  2. Checkpoint Inhibitor (CPI) Cohort: Pathological Complete Response (pCR)

    Scored by local pathologists; defined as lack of any viable tumor cells on review of hematoxylin and eosin (H\&E) slides after complete evaluation of a resected lung cancer specimen including all sampled regional lymph nodes.

    Measured: After surgical resection (approximately study Week 8)

  3. KRAS G12C Cohort: Percentage of Participants With 3-5 Grade Adverse Events (AEs)

    Measured: After surgical resection (approximately study Week 8)

  4. KRAS G12C Cohort: Percentage of Participants Without Delays of Surgery due to Treatment-related AEs as Reported by the Investigator

    Measured: After surgical resection (approximately study Week 8)

Secondary outcomes (11)

  1. Proportion of Participants With MPR

    Defined as ≤10% residual viable tumor cells) based on surgical resection as defined by Hellmann et al. (2014) and Travis et al. (2020). TKI cohorts: MPR will be scored by a central pathology committee consensus read. CPI cohort: MPR will be scored by local pathologists and central pathology committee consensus read. KRAS G12C cohort: MPR will be scored by local pathologists and central pathology committee consensus read.

    Measured: After surgical resection (approximately study Week 8)

  2. Proportion of Participants With pCR

    Defined as lack of any viable tumor cells on review of H\&E slides after complete evaluation of a resected lung cancer specimen, including all sampled regional lymph nodes.

    TKI cohorts: pCR will be scored by local pathologists and a central pathology committee consensus read.

    CPI cohort: pCR will be scored by a central pathology committee consensus read. KRAS G12C cohort: pCR will be scored by a central pathology committee consensus read.

    Measured: After surgical resection (approximately study Week 8)

  3. Pathological Regression Based on Weighted % Viable Tumor Cell Assessment

    Measured: After surgical resection (approximately study Week 8)

  4. Investigator-assessed Response Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)

    Measured: After neoadjuvant treatment (after approximately study Week 8)

  5. Disease-free Survival (DFS)

    Measured: From the first date of no disease to local or distant recurrence or death from any cause, whichever occurs first, through the end of the study (up to 9 years)

  6. Event-free Survival (EFS)

    Measured: From first dose of study treatment to first documented disease progression per RECIST v1.1, or local or distant disease recurrence as determined by investigator, or death from any cause, whichever occurs first, through the end of study (up to 9 years)

  7. Overall Survival (OS)

    Measured: From the first dose of study medication to death from any cause, through the end of the study (up to 9 years)

  8. Percentage of Participants With AEs

    Measured: Up to 9 years

  9. Nodal Downstaging

    Defined as percentage of participants with reduced stages in regional lymph nodes at surgery.

    Measured: After surgical resection (approximately study Week 8)

  10. Circulating tumor DNA (ctDNA) Clearance Rate

    Measured: Prior to surgery (before study Week 8)

  11. KRAS G12C Cohort: Plasma Concentration of Divarasib at Specified Timepoints

    • Treatment completion/discontinuation;
    • Disease Progression or Recurrence during Neoadjuvant treatment or Surveillance;
    • Unscheduled (Tumor Evaluation and Response) [Anytime up to 3 years]

    Measured: Neo-adjuvant: pre-dose & 2 hours post-dose on Day 1 of Cycles 1 & 2; Pre-surgery (before Week 8): pre-dose; Adjuvant treatment: pre-dose & 2 hours post-dose on Day 1 of Cycles 1-6, pre-dose on Day 1 of Cycle 9 (each cycle=28 days);

Timeline

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

  1. First posted10 Mar 2020
  2. Study start6 Nov 2020
  3. Primary completion30 Nov 2026 (estimated)
  4. Study completion30 May 2030 (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 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
99 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04302025
Sponsor's protocol ID
ML41591
Acronym
NAUTIKA1
Status last verified
Oct 2026
First submitted
6 Mar 2020
Last updated
13 Oct 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data\_sharing

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Alectinib, Entrectinib and Vemurafenib in people with Non-small Cell Lung Cancer, run by Genentech, Inc. at 38 sites 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 21 inclusion and 9 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: looking for participants now, as of the sponsor's last update on 13 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 38 sites 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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?

Contact Reference Study ID Number: ML41591 https://forpatients.roche.com/ No attachments to email below. (888-662-6728, global-roche-genentech-trials@gene.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Tyrosine Kinase Inhibitor (TKI) Cohort: Proportion of Participants With Major Pathologic Response (MPR) (time frame: After surgical resection (approximately study Week 8)). The study lists 4 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 NCT04302025.

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 13 Oct 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in