Amivantamab + TKI for Lung Cancer

Recruiting at 3 trial locations

Overseen By Febin Elias

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

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 All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

12 Participants Needed

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.

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

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

Who Is Running the Clinical Trial?

University of Colorado, Denver

Lead Sponsor

Trials

1,842

Recruited

3,028,000+

Janssen Research & Development, LLC

Industry Sponsor

Trials

1,022

Recruited

6,408,000+

Giacomo Salvadore

Janssen Research & Development, LLC

Chief Medical Officer since 2023

MD from the University of Rome, Tor Vergata

Ricardo Attar

Janssen Research & Development, LLC

Chief Executive Officer since 2008

PhD in Molecular Biology from the University of Buenos Aires

Findings from Research

Amivantamab is a bispecific monoclonal antibody that targets both EGFR and MET, specifically developed for treating non-small cell lung cancer (NSCLC) with EGFR Exon 20 insertion mutations.

It received its first approval in the USA on May 21, 2021, for adult patients with advanced NSCLC who have progressed after platinum-based chemotherapy, and is currently in preregistration in multiple countries including the EU and Japan.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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

In a study of 61 patients with advanced EGFR-mutant NSCLC, amivantamab showed a clinical response rate of 45.2% and a disease control rate of 64.3%, indicating its potential effectiveness beyond just exon 20 insertion mutations.

The combination of amivantamab with osimertinib and concurrent radiation therapy was found to be safe, with no additional toxicities reported, suggesting that this treatment approach could be a viable option for patients.

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]

Amivantamab, approved for treating non-small cell lung cancer with specific genetic mutations, works by targeting two pathways: the epithelial growth factor receptor and mesenchymal epithelial transition factor, enhancing the immune response against cancer cells.

Preclinical studies indicate that Amivantamab effectively inhibits cancer cell growth in models with exon20 insertions of the epithelial growth factor receptor, suggesting its potential as a targeted therapy for this specific patient population.

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]

Amivantamab-vmjw has shown a 40% overall response rate in patients with metastatic non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion mutations, based on a phase 1 trial involving 81 participants, indicating its efficacy after platinum-based chemotherapy.

The treatment resulted in a median progression-free survival of 8.3 months and an overall survival of 22.8 months, with an acceptable safety profile, marking it as a significant advancement for patients with limited treatment options.

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]

In a phase 3 trial involving 308 patients with advanced non-small-cell lung cancer (NSCLC) and EGFR exon 20 insertions, the combination of amivantamab and chemotherapy significantly improved progression-free survival compared to chemotherapy alone, with a median of 11.4 months versus 6.7 months.

The combination therapy also showed a higher response rate, with 73% of patients achieving a complete or partial response compared to 47% in the chemotherapy-only group, indicating that amivantamab enhances the effectiveness of standard chemotherapy in this patient population.

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]