Amivantamab With Tyrosine Kinase Inhibitor (TKI)

• Status: Not yet recruiting
• Trial end date: 2028-01-01
• Target enrollment: 0
• Participant gender: All

Summary

Although non-small cell lung cancer (NSCLC) patients with anaplastic lymphoma kinase (ALK), ROS Proto-Oncogene 1 (ROS1), and rearranged during transfection (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 (epidermal growth factor receptor (ERBB) or mesenchymal-epithelial transition (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.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Colorado, Denver
• Collaborator: Janssen Research & Development, LLC
• Treatments: Amivantamab-vmjw; Antibodies, Bispecific

Criteria

Inclusion Criteria:

1. Provision to sign and date the informed consent form.

2. Stated willingness to comply with all study procedures and be available for the duration of the study.

3. Participant is ≥ 18 years of age.

4. Participant has histologic or cytologic confirmation of locally advanced (unresectable) or metastatic NSCLC with a known (and documented) ALK, ROS1, or RET fusion based on approved diagnostic testing methods specified below a. IHC: For ALK NSCLC only using the ALK D5F3 antibody b. FISH with ≥15% of 100 cells sampled constituting positivity c. NGS using a CLIA-certified test

5. Participants must have clinical progression on at least one prior TKI. They must be on a TKI at the same dose for at least 3 months prior to enrolling on this study. TKIs that will be considered include (but not limited to):

1. ALK fusions - alectinib, brigatinib, lorlatinib

2. ROS1 fusions - entrectinib, lorlatinib

3. RET fusions - selpercatinib, pralsetinib

6. Participants must have at least 1 measurable lesion by RECIST v1.1 criteria using computed tomography (CT) scan or magnetic resonance imaging (MRI).

a. Measurable CNS lesions ≥10mm must be captured as overall and intracranial RECIST target lesions. CNS lesions 5-9mm may be included in the intra-cranial data set alone but must be listed as non-target lesions. b. Measurable, treated brain metastases (≥ 10mm) growing after whole-brain radiotherapy (WBRT) or resection are allowed as target lesions, but lesions growing after stereotactic radiosurgery (SRS) are allowed as target lesions only if radiation necrosis or pseudoprogression is ruled out.

7. Participant has an Eastern Cooperative Oncology Group (ECOG) score of 0-2

8. Participant has a life expectancy of greater than 12 weeks, per investigator discretion.

9. Participant can ingest oral medications.

10. Participant has received the final dose of any of the following treatments/procedures*† with the specified minimum intervals before the first dose of study drug (unless in the opinion of the Sponsor-Investigator, the medication will not interfere with the study or compromise participant safety).

Chemotherapy‡ 21 days Antibody-drug conjugate (ADC) 28 days Immune checkpoint inhibitors (ICI) 28 days Locally ablative radiotherapy§ 28 days Palliative radiotherapy§ 14 days Major surgery 28 days

*The patient cannot have received an EGFR TKI (e.g. osimertinib, afatinib), EGFR-directed monoclonal antibody (e.g. cetuximab), MET-inhibitor (e.g., tepotinib, capmatinib, telisotuzumab vedotin, etc.) at any point prior to study entry. For patients with ALK and ROS1 NSCLC, crizotinib cannot be used within 3 months of screening.

† Patients will be allowed to remain on their prior TKI without need for a washout therapy.

‡ Chemotherapy washout period will be 21 days or 5 half-lives, whichever is longer. As patients are required to be on a stable dose of TKI for 3 months prior to study entry, this criterion would rarely (if ever) apply to any participant in this study.

§ Locally ablative therapy will be considered as any form of radiotherapy with the intent of providing ablative doses for oligoprogressive lesions while on TKI therapy. Palliative radiotherapy will be considered as any form of radiotherapy with the intent of alleviating symptomatic lesions.

Exclusion Criteria:

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