Amivantamab + TKI for Lung Cancer

Recruiting in Palo Alto (17 mi)

+3 other locations

Overseen by Patil Tejas, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: University of Colorado, Denver

Must be taking: TKIs

Must not be taking: EGFR TKIs, MET TKIs

Disqualifiers: Cardiovascular disease, ILD, Hepatitis, others

No Placebo Group

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

Although non-small cell lung cancer (NSCLC) patients with anaplastic lymphoma kinase (ALK), c-ros oncogene 1(ROS1), and ret proto-oncogene (RET) gene fusions initially respond well to tyrosine kinase inhibitor (TKI) therapies, acquired resistance is inevitable. In many of these cases, increased activation of the erythroblastic leukemia viral oncogene homologue (ERBB) or cMet pathways appears to be a bypass signaling mechanism that allows these cancer cells to circumvent the selective pressure from TKIs. Recent data have suggested that these pathways compensate for each other in situations where one pathway is inhibited, leading to "kinase switch" drug resistance. Thus, the expected inhibition of both pathways via treatment with the amivantamab and combination TKI combination may improve overall efficacy by limiting the compensatory pathway activation.

Will I have to stop taking my current medications?

The trial requires participants to have been on a TKI (a type of cancer medication) at the same dose for at least 8 weeks before enrolling, without any new progression or intolerance. The protocol does not specify if you need to stop other medications, but you should discuss your current medications with the study team to ensure they won't interfere with the trial.

What data supports the effectiveness of the drug Amivantamab for lung cancer?

Amivantamab has been approved for treating advanced non-small cell lung cancer (NSCLC) with specific genetic changes (EGFR Exon 20 insertion mutations) after other treatments have failed, showing it can help patients whose cancer has progressed despite previous chemotherapy. ^{1 2 3 4 5}

Is Amivantamab safe for humans?

Amivantamab, also known as Rybrevant, has been approved for use in treating certain types of lung cancer, and studies have shown it to be generally safe when used with chemotherapy. However, more data is needed to fully understand its safety when combined with other treatments. ^{1 2 3 4 5}

What makes the drug Amivantamab unique for treating lung cancer?

Amivantamab is unique because it is a bispecific antibody that targets both EGFR and MET, specifically designed for non-small cell lung cancer (NSCLC) with EGFR Exon 20 insertion mutations, especially after other treatments like platinum-based chemotherapy have failed. ^{1 2 3 4 5}

Research Team

Patil Tejas, MD

Principal Investigator

University of Colorado, Denver

Eligibility Criteria

Adults with advanced NSCLC who have ALK, ROS1, or RET gene fusions and have seen their cancer progress after at least one TKI treatment. They must be currently on a stable dose of TKI for 3+ months, able to take oral meds, and have a life expectancy over 12 weeks. Excluded are those with certain prior treatments, active infections like HIV or hepatitis B/C, pregnant women, and anyone with severe allergies to study drugs.

Inclusion Criteria

I am 18 years old or older.

I have completed all my previous treatments as required before starting the study drug.

It has been over 21 days or 5 half-lives since my last chemotherapy.

Exclusion Criteria

I have active symptoms from a brain or spinal cord condition.

My biopsy shows signs of neuroendocrine differentiation or small cell transformation.

I have never been treated with specific targeted lung cancer drugs before joining this study.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Finding (Safety Lead-In)

To estimate the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) in adult participants with advanced NSCLC with ALK, ROS1, and RET gene fusions

18 months

Dose Expansion

To estimate the objective response rate (ORR) of amivantamab in combination with common TKIs used in ALK, ROS1, and RET advanced NSCLC progressing on TKIs

40 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

Treatment Details

Interventions

• Amivantamab (Monoclonal Antibodies)

Trial Overview The trial is testing Amivantamab in combination with current TKI therapies against advanced non-small cell lung cancer (NSCLC) that has specific genetic alterations (ALK, ROS1, RET). The goal is to see if this combo can overcome resistance developed from previous treatments by inhibiting pathways that the cancer cells use to survive.

Participant Groups

Group I: Dose Finding (Safety Lead-In) Cohort (≥80 kg) Experimental Treatment 1 Intervention

To estimate the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) in adult participants with advanced NSCLC with ALK, ROS1, and RET gene fusions.

Group II: Dose Finding (Safety Lead-In) Cohort (<80 kg) Experimental Treatment 1 Intervention

To estimate the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) in adult participants with advanced NSCLC with ALK, ROS1, and RET gene fusions.

Group III: Dose Expansion Cohort (≥80 kg) Experimental Treatment 1 Intervention

To estimate the objective response rate (ORR) of amivantamab in combination with common TKIs used in ALK, ROS1, and RET advanced NSCLC progressing on TKIs.

Group IV: Dose Expansion Cohort (<80 kg) Experimental Treatment 1 Intervention

To estimate the objective response rate (ORR) of amivantamab in combination with common TKIs used in ALK, ROS1, and RET advanced NSCLC progressing on TKIs.

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Colorado Research Center Aurora, CO

University of Michigan Rogel Cancer Center Ann Arbor, MI

Outpatient CTRC Aurora, CO

UCHealth Metro Denver Aurora, CO

Who Is Running the Clinical Trial?

University of Colorado, Denver

Lead Sponsor

Trials

1842

Patients Recruited

3,028,000+

Janssen Research & Development, LLC

Industry Sponsor

Trials

1022

Patients Recruited

6,408,000+

Findings from Research

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amivantamab: First Approval. Syed, YY.[2021]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

BRIEF REPORT: Real-world efficacy and safety of amivantamab for EGFR-mutant non-small cell lung cancer (NSCLC). Wang, K., Du, R., Myall, NJ., et al.[2023]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amivantamab: A New Hope in Targeting Non-small Cell Lung Cancer. Billowria, K., Das Gupta, G., Chawla, PA.[2023]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amivantamab-Vmjw: A Novel Treatment for Patients with NSCLC Harboring EGFR Exon 20 Insertion Mutation after Progression on Platinum-Based Chemotherapy. Shah, V., McNatty, A., Simpson, L., et al.[2023]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amivantamab plus Chemotherapy in NSCLC with EGFR Exon 20 Insertions. Zhou, C., Tang, KJ., Cho, BC., et al.[2023]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Amivantamab: First Approval. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

BRIEF REPORT: Real-world efficacy and safety of amivantamab for EGFR-mutant non-small cell lung cancer (NSCLC). [2023]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Amivantamab: A New Hope in Targeting Non-small Cell Lung Cancer. [2023]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Amivantamab-Vmjw: A Novel Treatment for Patients with NSCLC Harboring EGFR Exon 20 Insertion Mutation after Progression on Platinum-Based Chemotherapy. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Amivantamab plus Chemotherapy in NSCLC with EGFR Exon 20 Insertions. [2023]