Active — Not RecruitingPhase 1/2

Amivantamab With Tyrosine Kinase Inhibitors (TKI) for Advanced NSCLC With ALK, ROS1, or RET Alterations

United States12 participantsStarted 2023-07-17

Plain-language summary

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.

Who can participate

Age range18 Years

SexALL

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Inclusion criteria

✓. Provision to sign and date the informed consent form.
✓. Stated willingness to comply with all study procedures and be available for the duration of the study.
✓. Participant is ≥ 18 years of age.
✓. 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. Not that NGS testing is required for all participants, but screening if any of the test below are positive.
✓. Participants must have clinical progression on at least one prior FDA-approved TKI. They must be on a TKI at the same dose for at least 8 weeks without radiographic progression or clinical intolerance of the TKI prior to enrolling on this study. TKIs that will be considered include (but not limited to):
✓. ALK fusions - alectinib, brigatinib, lorlatinib
✓. ROS1 fusions - entrectinib, lorlatinib
✓. RET fusions - selpercatinib, pralsetinib

Exclusion criteria

What they're measuring

Determine the MTD in adult participants with advanced NSCLC

Timeframe: 18 months

Determine the recommended phase 2 dose in adult participants with advanced NSCLC

Timeframe: 20 months

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

Timeframe: 40 months

Trial details

NCT IDNCT05845671

SponsorUniversity of Colorado, Denver

Sponsor typeOTHER

Study typeINTERVENTIONAL

Primary completion2027-01

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