HER3-DXd + Osimertinib for Non-Small Cell Lung Cancer

Recruiting in Palo Alto (17 mi)

+32 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Waitlist Available

Sponsor: Daiichi Sankyo

No Placebo Group

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This study includes a Dose Escalation Part to identify the recommended combination dose (RCD) and a Dose Expansion Part to further evaluate efficacy and safety. The primary objectives: Dose Escalation: To assess the safety and tolerability of HER3-DXd (patritumab deruxtecan; U3-1402) and osimertinib in subjects with locally advanced or metastatic non-small cell lung cancer (NSCLC) with an EGFR exon 19 deletion or L858R mutation with tumor progression after treatment with osimertinib, and to determine the recommended combination dose (RCD). Second-Line Dose Expansion Arm 1 and Arm 1b: To assess the preliminary antitumor activity of HER3-DXd and osimertinib in subjects with locally advanced or metastatic NSCLC with an EGFR exon 19 deletion or L858R mutation with tumor progression after treatment with osimertinib. Note: One or both of the study arms may open with one or two distinct dosing schedules. Second-Line Dose Expansion Arm 2: To assess the preliminary antitumor activity of HER3-DXd monotherapy in subjects with locally advanced or metastatic NSCLC with an EGFR exon 19 deletion or L858R mutation with tumor progression after treatment with osimertinib. First-Line Dose Expansion Cohorts 3, 4a, and 4b: To assess the preliminary antitumor activity of HER3-DXd and osimertinib in subjects with locally advanced or metastatic NSCLC with an EGFR exon 19 deletion or L858R mutation without prior systemic treatment for locally advanced or metastatic disease.

Eligibility Criteria

This trial is for adults with advanced or metastatic non-small cell lung cancer (NSCLC) that has specific mutations (EGFR exon 19 deletion or L858R). Participants must have progressed after osimertinib treatment, not received other systemic cancer therapies in the advanced setting, and have adequate organ function. Those with significant cardiovascular disease, uncontrolled diseases, certain lung conditions, active brain metastases requiring steroids or anticonvulsants, a history of interstitial lung disease, or on high-dose corticosteroids are excluded.

Inclusion Criteria

I have advanced lung cancer and haven't been treated with osimertinib yet.

Participants must meet all criteria to be eligible for inclusion in this study

My lung cancer cannot be cured with surgery or radiation.

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Exclusion Criteria

My side effects from previous cancer treatments are mostly gone or mild.

I am on long-term steroids or immunosuppressants, but I can use inhaled or topical steroids.

I do not have active brain metastases requiring steroids or seizure medications.

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Treatment Details

Interventions

Osimertinib (Tyrosine Kinase Inhibitor)
Patritumab Deruxtecan (Monoclonal Antibodies)

Trial OverviewThe study tests HER3-DXd combined with osimertinib to find the safest dose and assess its effectiveness against NSCLC. It includes initial dose escalation to determine the recommended combination dose followed by expansion phases to evaluate efficacy in different patient groups based on prior treatments.

Participant Groups

6Treatment groups

Experimental Treatment

Group I: Second-line Dose Expansion: HER3-DXd + osimertinib (RCD)Experimental Treatment2 Interventions

Participants in the Second-line Dose Expansion phase will be randomized to receive HER3-DXd + osimertinib at the RCD

Group II: Second-line Dose Expansion: HER3-DXdExperimental Treatment1 Intervention

Participants in the Second-line Dose Expansion phase will be randomized to receive HER3-DXd 5.6 mg/kg IV Q3W

Group III: First-line Dose Expansion: HER3-DXd + osimertinib (Cohort 4b)Experimental Treatment2 Interventions

Participants in the First-line Dose Expansion phase will be randomized to receive HER3-DXd 4.8 mg/kg IV Q3W and osimertinib dose of 80 mg PO once daily.

Group IV: First-line Dose Expansion: HER3-DXd + osimertinib (Cohort 4a)Experimental Treatment2 Interventions

Participants in the First-line Dose Expansion phase will be randomized to receive HER3-DXd 5.6 mg/kg IV Q3W and osimertinib dose of 80 mg PO once daily.

Group V: First-line Dose Expansion: HER3-DXd + osimertinib (Cohort 3; RCD)Experimental Treatment2 Interventions

If the RCD includes an osimertinib dose of 80 mg PO once daily, then participants will receive treatment with HER3-DXd and osimertinib at the RCD

Group VI: Dose Escalation: HER3-DXd + osimertinibExperimental Treatment2 Interventions

Participants in the Dose Escalation phase will receive HER3-DXd IV Q3W + osimertinib PO once daily. The dose of HER3-DXd in the first cohort will be 3.2 mg/kg Q3W. The dose of osimertinib in the first cohort will be 80 mg PO once daily.

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

🇺🇸 Approved in United States as Tagrisso for:

Locally advanced or metastatic non-small-cell lung cancer (NSCLC) with EGFR exon 19 deletions or exon 21 L858R mutations
Metastatic EGFR T790M mutation-positive NSCLC

🇪🇺 Approved in European Union as Tagrisso for:

Locally advanced or metastatic non-small-cell lung cancer (NSCLC) with EGFR exon 19 deletions or exon 21 L858R mutations
Metastatic EGFR T790M mutation-positive NSCLC