Collaborative Clinical-translational Cohort of Amivantamab Plus Lazertinib and Amivantamab Plus Chemotherapy in Patients With EGFR-mutant, Locally Advanced or Metastatic/Recurrent Non-Small Cell Lung Cancer (INSTAR Study)

Plain English Summary

Collaborative Clinical-translational Cohort of Amivantamab Plus Lazertinib and Amivantamab Plus Chemotherapy in Patients With EGFR-mutant, Locally Advanced or Metastatic/Recurrent Non-Small Cell Lung Cancer (INSTAR Study) is a Phase 2 clinical trial sponsored by Yonsei University studying Non Small Cell Lung Cancer. This trial tests amivantamab combined with either lazertinib or chemotherapy for specific types of non-small cell lung cancer. It is for patients with EGFR-mutant, locally advanced, or metastatic/recurrent non-small cell lung cancer. Participation involves receiving study drugs and undergoing tumor biopsies. Alternative treatments may include other targeted therapies or chemotherapy depending on prior treatment history. The trial aims to enroll 80 participants.

Official Summary

* In this study, we hypothesized that immune engagement by amivantamab will enhance antitumor efficacy by modulating the immune microenvironment in combination with lazertinib in patients with untreated EGFR-mutant NSCLC or with chemotherapy (carboplatin plus pemetrexed) after progression with 3rd generation (3G) EGFR TKI. * The primary objective of this study is to examine the patients' tumors for immunomodulatory effects of amivantamab-based regimens. * In a phase 2, two cohort clinical trial, treatment naïve patients with EGFR-mutant NSCLC will be treated with amivantamab SC plus oral lazertinib (Cohort 1, n=30) or patients with EGFR-mutant NSCLC progressed on or after 3G EGFR TKI treated with amivantamab SC plus chemotherapy (Cohort 2, n=30).

Who Can Participate

Here is what you need to know about eligibility for this trial. Patients must be 19 years or older with a confirmed diagnosis of non-small cell lung cancer and a specific EGFR gene mutation (Exon 19 deletion or L858R). Patients should have measurable disease and a good general health status (ECOG performance status 0-1) with no significant organ dysfunction. Individuals who have not previously received treatment for their advanced cancer or whose cancer has progressed after a specific type of prior therapy may be eligible. This trial is studying Non Small Cell Lung Cancer, so participants generally need a confirmed diagnosis.

What They're Measuring

The primary goal is to understand how the study drugs affect the tumor's environment and its interaction with the immune system, which could lead to more effective treatments. The specific primary outcome measures are: • scRNA-seq and/or spatial RNA sequencing analysis. Multiplex IHC and/or FACS analysis. (through study completion, an average of 5 year). 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 treatment outcomes for a specific group of lung cancer patients by exploring novel combinations of therapies that may enhance the immune system's ability to fight cancer. 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 Phase 2 trial investigates a combination therapy for a subset of non-small cell lung cancer patients, potentially addressing an unmet need in EGFR-mutant lung cancer treatment and signaling inter Phase 2 trials have approximately a 15-20% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor about the specific drugs being tested, how they will be given, and what side effects are possible. Be prepared for regular clinic visits for drug administration, blood tests, and tumor biopsies. Understand that this is a research study, and the treatments may or may not be more effective than standard care. The trial is being conducted at multiple 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: 80 participants

Interventions

• DRUG: Amivantamab SC + Lazertinib PO — • Amivantamab SC plus Lazertinib PO: 28-day Cycles * Amivantamab 1600/2240 mg SC QW up to C2D1 and Q2W thereafter; * Lazertinib 240 mg PO QD
• DRUG: Amivantamab SC + Chemotherapy (Carboplatin IV & Pemetrexed IV) — * Amivantamab SC plus Chemotherapy: 21-day Cycles 1-4 * Amivantamab 1600/2240 mg SC C1D1; 2400/3360 mg C1D8, C1D15, and Day 1 of Cycles 2, 3, 4 * Pemetrexced 500 mg/m2 IV Day 1 * Carboplatin AUC5 IV Day 1 * Amivantamab SC plus Chemotherapy: 21-day Cycles 5+ * Amivantamab 2400/3360 mg SC Day 1 * Pemetrexed 500 mg/m2 IV Day 1

Primary Outcomes

• • scRNA-seq and/or spatial RNA sequencing analysis. Multiplex IHC and/or FACS analysis. (through study completion, an average of 5 year)

Secondary Outcomes

• Objective Response rate (ORR) (through study completion, an average of 5 year)
• Progression-free survival (PFS) (through study completion, an average of 5 year)
• Duration of response (DoR) (through study completion, an average of 5 year)
• circulating tumor DNA (ctDNA). (through study completion, an average of 5 year)

Full Eligibility Criteria

Inclusion Criteria:

1. 19 years and older
2. Provision of informed consent prior to any study specific procedures
3. Histologically or cytologically confirmed Locally advanced, Recurrent, or Metastatic NSCLC, performed on a biopsy and able to do a paired biopsy during treatment (C3D1)
4. Documented activating EGFR mutation (Exon 19 deletion or L858R)
5. Measurable disease defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria
6. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0-1
7. Resolution of all acute toxic effects of prior chemotherapy, radiotherapy or surgical procedures to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0: ≤ grade 1
8. Patient should meet following requirements.

   * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x upper limit of normal (ULN)
   * Bilirubin ≤ 1.5 x ULN, (Patients with documented Gilbert's syndrome and conjugated bilirubin within the normal range may be allowed into the study; in this event, it will be documented that the patient was eligible based on conjugated bilirubin levels)
   * Leukocytes ≥ 3.0 x 10\^3/μL
   * Hemoglobin ≥ 9.0 g/dL, with no blood transfusions in the 28 days prior to study entry
   * Absolute neutrophil count ≥ 1.5 x 10\^3/μL
   * Platelets ≥ 75 x 10\^3/μL
   * Creatinine ≤ 1.5 x upper limit of normal (ULN) OR creatinine clearance (details in Appendix 10. Cockcroft-Gault Formula for Estimated Creatinine Clearance) \>50 mL/min for patients with creatinine levels \>1.5 x upper limit above institutional normal
9. Ability to swallow oral medications
10. Male or female (according to their reproductive organs and functions assigned by chromosomal complement at birth).
11. A female using oral contraceptivesmust use an additional barrier contraceptive method (details in Appendix 5: Contraceptive Guidance). A female participant must be either of the following (as defined in Appendix 5: Contraceptive Guidance)

    1. Not of childbearing potential: premenarchal; postmenopausal (\>45 years of age with amenorrhea for at least 12 months); permanently sterilized (eg, bilateral tubal occlusion, hysterectomy, bilateral salpingectomy, bilateral oophorectomy); or otherwise, be incapable of pregnancy.
    2. Of childbearing potential and practicing at least 1 highly effective method(s) of birth control consistent with local regulations regarding the use of birth control methods for participants participating in clinical studies, as described below:

       * Practicing true abstinence (when this is in line with the preferred and usual lifestyle of the participant), which is defined as refraining from heterosexual intercourse during the entire period of the study, and for 7 months after the last dose of the study treatment. Periodic abstinence (calendar, symptothermal, post-ovulation methods) is not considered an acceptable contraceptive method.
       * Have a sole partner who is vasectomized.
       * Practicing 2 methods of contraception, including one highly effective method (ie, established use of oral, intravaginal, transdermal, injected or implanted hormonal methods of contraception; placement of an intrauterine device \[IUD\] or intrauterine system \[IUS\], tubal ligation procedures as consistent with local regulations), AND, a second method, (eg, condom with spermicidal foam/gel/film/cream/suppository or occlusive cap \[diaphragm or cervical/vault caps\] with spermicidal foam/gel/film/cream/suppository).
       * Participants must agree to continue contraception throughout the study and continuing through 7 months after the last dose of the study treatment.

    Note: If the childbearing potential changes after start of the study (eg, woman who is not heterosexually active becomes active, premenarchal woman experiences menarche) the woman must begin a method of birth control, including 1 highly effective method, as described above.
12. A female participant of childbearing potential must have a negative serum (b-human chorionic gonadotropin \[b-hCG\]) at screening (within 72 hours of the first dose of study treatment administration) and must agree to further serum or urine pregnancy tests during the study prior to Day 1 of each cycle and at End of Study.
13. A female must agree not to donate eggs (ova, oocytes) or freeze for future use for the purposes of assisted reproduction during the study and for a period of 7 months after the last dose of the study treatment. Female participants should consider preservation of eggs prior to study treatment as anti-cancer treatments may impair fertility.
14. A male participant must wear a condom when engaging in any activity that allows for passage of ejaculate to another person during the study and for 6 months after the last dose of the study treatment.
15. If the male participant's partner is a female of childbearing potential, the male participant must use condom with or without spermicide and 

Frequently Asked Questions

Related Conditions

• Non-Small Cell Lung Cancer
• EGFR-mutant Lung Cancer
• Metastatic Lung Cancer
• Recurrent Lung Cancer
• Advanced Lung Cancer
• Lung Adenocarcinoma
• Thoracic Oncology
• Oncology
• Cancer Immunotherapy
• Targeted Cancer Therapy

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