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}

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.

Amivantamab is already approved in United States, European Union for the following indications:

🇺🇸 Approved in United States as Rybrevant for:

• Locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations
• Locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations

🇪🇺 Approved in European Union as Rybrevant for:

• Locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations
• Locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations

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

Janssen Research & Development, LLC Industry Sponsor

References

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

Amivantamab: First Approval. [2021] Amivantamab (amivantamab-vmjw; Rybrevant™), a bispecific monoclonal antibody targeting epidermal growth factor receptor (EGFR) and mesenchymal epithelial transition factor (MET), is being developed by Janssen Biotech for the treatment of non-small cell lung cancer (NSCLC). On 21 May 2021, amivantamab received its first approval in the USA for the treatment of adult patients with locally advanced or metastatic NSCLC harbouring EGFR Exon 20 insertion mutations whose disease has progressed on or after platinum-based chemotherapy. Amivantamab is in preregistration for NSCLC in the EU, Australia, Japan, Canada, Switzerland and China. This article summarizes the milestones in the development of amivantamab leading to this first approval for NSCLC.

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] Amivantamab-vmjw (amivantamab) is a bispecific EGFR/MET antibody approved for patients with advanced non-small cell lung cancer (NSCLC) with EGFR Exon 20 insertion mutations, after prior therapy. However, the benefits and safety of amivantamab in other EGFR-mutation lung cancer, with or without osimertinib, and with concurrent radiation therapy, are less known.

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

Amivantamab: A New Hope in Targeting Non-small Cell Lung Cancer. [2023] Amivantamab was approved on May 21st, 2021, by United States food and drug administration with the brand name Rybervant, used particularly for adult patients with exon20 insertion of epithelial growth factor receptor with locally advanced metastatic non-small cell lung cancer.

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] This study is a comprehensive review of the clinical pharmacology, pharmacokinetics, efficacy, safety, and clinical applicability of amivantamab-vmjw for metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion (exon20ins) mutation.

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

Amivantamab plus Chemotherapy in NSCLC with EGFR Exon 20 Insertions. [2023] Label="BACKGROUND" NlmCategory="BACKGROUND">Amivantamab has been approved for the treatment of patients with advanced non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertions who have had disease progression during or after platinum-based chemotherapy. Phase 1 data showed the safety and antitumor activity of amivantamab plus carboplatin-pemetrexed (chemotherapy). Additional data on this combination therapy are needed.