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

Plain English Summary

A Study of Multiple Therapies in Biomarker-selected Participants With Resectable Stages IB-III Non-small Cell Lung Cancer (NSCLC) is a Phase 2 clinical trial sponsored by Genentech, Inc. studying Non-small Cell Lung Cancer. This trial tests different targeted drug combinations to see how well they work in shrinking lung tumors before surgery. It is for patients with early-stage non-small cell lung cancer (NSCLC) that can be removed by surgery and has specific genetic markers. Participants will receive one of the study drugs before surgery, followed by surgery, and potentially more treatment after surgery. Standard treatment for this type of lung cancer typically involves surgery alone or surgery with chemotherapy/radiation. The trial aims to enroll 99 participants.

Official 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.

Who Can Participate

Here is what you need to know about eligibility for this trial. You can join if you have newly diagnosed, operable non-small cell lung cancer (stages IB-IIIB) with specific genetic changes like ALK, ROS1, NTRK, BRAF, RET fusions, or PD-L1 expression of 1% or more, or a KRAS G12C mutation. You cannot join if your cancer has spread to vital organs, if you've had lung cancer treatment in the last 2 years, or if you have other serious medical conditions. You must be between 18 and 80 years old and have good general health and organ function to be able to undergo surgery. You need to have a specific type of lung cancer that can be fully removed by surgery and have specific genetic markers tested. This trial is studying Non-small Cell Lung Cancer, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The main goal is to see how many patients have their tumors significantly reduced or eliminated after treatment before surgery, which could mean the treatment is effective at fighting the cancer. The specific primary outcome measures are: Tyrosine Kinase Inhibitor (TKI) Cohort: Proportion of Participants With Major Pathologic Response (MPR) (After surgical resection (approximately study Week 8)); Checkpoint Inhibitor (CPI) Cohort: Pathological Complete Response (pCR) (After surgical resection (approximately study Week 8)); KRAS Cohort: Percentage of Participants With 3-5 Grade Adverse Events (AEs) (After surgical resection (approximately study Week 8)); KRAS Cohort: Percentage of Participants Without Delays of Surgery due to Treatment-related Adverse Events as Reported by the Investigator (After surgical resection (approximately study Week 8)). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 2, which tests whether the treatment actually works against the target condition. Phase 2 trials involve 100-300 patients and continue to monitor safety while evaluating effectiveness. This phase often tests different dosages to find the optimal amount. About 33% of Phase 2 drugs advance to Phase 3. If successful, the treatment will move to large-scale Phase 3 trials needed for FDA approval.

Why This Trial Matters

This trial aims to improve outcomes for early-stage lung cancer patients by using targeted therapies to shrink tumors before surgery, potentially leading to better surgical results and fewer recurrenc Phase 2 success would typically lead to larger Phase 3 trials needed for regulatory approval. This research targets Non-small Cell Lung Cancer, where improved treatment options are needed.

Investor Insight

This trial targets a growing market for precision oncology in lung cancer, focusing on biomarker-selected patients, which could lead to more effective and personalized treatments if successful. Phase 2 trials have approximately a 15-20% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor if your lung cancer has the specific genetic markers (biomarkers) needed for this trial. Understand that you will receive study drugs before surgery, undergo surgery, and may need further treatment afterwards. Be prepared for regular clinic visits for tests, drug administration, and monitoring of side effects. This trial is currently recruiting participants. The trial is being conducted at 20 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: NON_RANDOMIZED
• Model: SINGLE_GROUP
• Masking: NONE
• Enrollment: 99 participants

Interventions

• DRUG: Alectinib — Participants will receive oral alectinib twice per day (BID).
• DRUG: Entrectinib — Participants will receive oral entrectinib daily.
• DRUG: Vemurafenib — Participants will receive oral vemurafenib BID.
• DRUG: Cobimetinib — Participants will receive oral cobimetinib daily.
• DRUG: Pralsetinib — Participants will receive oral pralsetinib daily.

Primary Outcomes

• Tyrosine Kinase Inhibitor (TKI) Cohort: Proportion of Participants With Major Pathologic Response (MPR) (After surgical resection (approximately study Week 8))
• Checkpoint Inhibitor (CPI) Cohort: Pathological Complete Response (pCR) (After surgical resection (approximately study Week 8))
• KRAS Cohort: Percentage of Participants With 3-5 Grade Adverse Events (AEs) (After surgical resection (approximately study Week 8))
• KRAS Cohort: Percentage of Participants Without Delays of Surgery due to Treatment-related Adverse Events as Reported by the Investigator (After surgical resection (approximately study Week 8))

Secondary Outcomes

• Proportion of Participants With MPR (After surgical resection (approximately study Week 8))
• Proportion of Participants With pCR (After surgical resection (approximately study Week 8))
• Pathological Regression Based on Weighted % Viable Tumor Cell Assessment (After surgical resection (approximately study Week 8))
• Investigator-assessed Response Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) (After neoadjuvant treatment (after approximately study Week 8))
• Pathological Complete Response (pCR) as Assessed by Local and Central Pathology Laboratories (At the time of surgical resection (approximately study Week 8))

Full Eligibility Criteria

Inclusion Criteria for Neoadjuvant Therapy:

* 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 mediastinoscopyor endo- bronchial ultrasonography is highly encouraged for participants with radiographically suspected mediastinal nodal disease (ie, 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 FDA-approved test, KRAS G12C mutation
* Measurable disease, as defined by RECIST v1.1
* 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

Exclusion Criteria

* 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
* 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

• City of Hope Comprehensive Cancer Center, Duarte, California, United States
• City of Hope - Orange County Lennar Foundation Cancer Center, Irvine, California, United States
• USC Norris Cancer Center, Los Angeles, California, United States
• Cedars-Sinai Medical Center, Los Angeles, California, United States
• University of California Los Angeles - Jonsson Comprehensive Cancer Center, Los Angeles, California, United States
• The Center for Cancer Prevention and Treatment at St.Joseph Hospital of Orange, Orange, California, United States
• UC Davis Comprehensive Cancer Center, Sacramento, California, United States
• UCSF Helen Diller Family CCC, San Francisco, California, United States
• University of Colorado - Anschutz Medical Campus (University of Colorado Health Sciences Center), Aurora, Colorado, United States
• Yale Cancer Center, New Haven, Connecticut, United States
• ...and 10 more locations

Frequently Asked Questions

Related Conditions

• Non-small Cell Lung Cancer
• Adenocarcinoma of the Lung
• Squamous Cell Carcinoma of the Lung
• ALK-positive Lung Cancer
• ROS1-positive Lung Cancer
• NTRK-positive Lung Cancer
• BRAF-mutated Lung Cancer
• RET-fusion Lung Cancer
• KRAS G12C-mutated Lung Cancer
• PD-L1 Positive Lung Cancer

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