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Tyrosine Kinase Inhibitor

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

Phase 1

Waitlist Available

Research Sponsored by Daiichi Sankyo

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Histologically or cytologically documented locally advanced or metastatic NSCLC not amenable to curative surgery or radiation

The tumor tissue harbors one of the 2 common EGFR mutations occurring in NSCLC known to be associated with EGFR-TKI sensitivity (exon 19 deletion or L858R) as assessed by Clinical Laboratory Improvement Amendments (CLIA)-certified (United States [US] sites), accredited (outside of the US), local laboratory or central laboratory. Only tissue-based testing will be accepted

Must not have

Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow osimertinib, or previous significant bowel resection that would preclude adequate absorption of osimertinib

Inadequate washout period prior to Cycle 1, Day 1 defined as: Whole brain radiation therapy <14 days or stereotactic brain radiation therapy <7 days; Any systemic anticancer therapy (excluding osimertinib in all Dose Escalation Cohorts and in Second-line Dose Expansion [Arm 1, Arm 2, and Arm 1b]), including investigational agents, <14 days or 5 half-lives, whichever is longer; Immune checkpoint inhibitor therapy <5 half-lives; Major surgery (excluding placement of vascular access) <4 weeks; Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation < 28 days or palliative radiation therapy <14 days; Chloroquine or hydroxychloroquine ≤14 days; Medications or herbal supplemented known to be strong inducers of cytochrome P450 (CYP) 3A4 <21 days

Timeline

Screening 3 weeks

Treatment Varies

Follow Up from the start of study treatment until the end of treatment or study discontinuation (whichever occurs first), up to approximately 9 months (dose escalation) and 18 months (dose expansion)

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a combination of two drugs, patritumab deruxtecan and osimertinib, to see if it is safe and effective in treating patients with lung cancer that has progressed after treatment with osimertinib. The study will also look at the preliminary antitumor activity of patritumab deruxtecan monotherapy in patients who have not responded to osimertinib.

Who is the study for?

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.

What is being tested?

The 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.

What are the potential side effects?

Potential side effects may include reactions at the infusion site, fatigue, nausea and vomiting issues related to digestion; blood disorders; increased risk of infections; potential heart-related complications such as abnormal heartbeat; and possible inflammation of organs like lungs leading to breathing difficulties.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My lung cancer cannot be cured with surgery or radiation.

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My lung cancer has a specific mutation known to respond to certain treatments.

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I have at least one tumor that can be measured.

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I have been taking osimertinib 80 mg daily for at least 6 weeks and haven't missed more than two doses in the last 2 weeks.

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My cancer has worsened after first-line treatment with osimertinib.

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I haven't had any systemic cancer treatments for my advanced cancer.

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My cancer has a specific EGFR mutation.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I cannot take osimertinib due to severe nausea, vomiting, gut diseases, surgery, or swallowing issues.

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I have not had certain treatments or surgeries recently before starting this trial.

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I have or might have a lung condition like ILD.

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My cancer has been confirmed as small cell or mixed small cell/non-small cell.

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I do not have significant heart problems or uncontrolled diseases.

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My cancer has spread to the lining of my brain and spinal cord.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ from the start of study treatment until the end of treatment or study discontinuation (whichever occurs first), up to approximately 9 months (dose escalation) and 18 months (dose expansion)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~from the start of study treatment until the end of treatment or study discontinuation (whichever occurs first), up to approximately 9 months (dose escalation) and 18 months (dose expansion)

This trial's timeline: 3 weeks for screening, Varies for treatment, and from the start of study treatment until the end of treatment or study discontinuation (whichever occurs first), up to approximately 9 months (dose escalation) and 18 months (dose expansion) for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Dose Escalation: Incidence of Dose-limiting Toxicities (DLT), Treatment-emergent Adverse Events (TEAE), Serious Adverse Events (SAE), Adverse Events of Special Interest (AESI)

Secondary study objectives

Dose Escalation, Second-line Dose Expansion, and First-Line Dose Expansion: Duration of Response (DoR)

Dose Escalation, Second-line Dose Expansion, and First-line Dose Expansion: Disease Control Rate (DCR)

Dose Escalation, Second-line Dose Expansion, and First-line Dose Expansion: Overall Survival (OS)

+10 more

Side effects data

From 2020 Phase 4 trial • 60 Patients • NCT03853551

10%

Blood creatine phosphokinase increased

10%

Fatigue

Decreased appetite

Diarrhoea

Cough

Mucosal inflammation

Rash

Pain in extremity

Constipation

Thrombocytopenia

Paronychia

Dyspnoea

Dengue fever

Disease progression

Cardio-respiratory arrest

Cataract

Mouth Ulceration

Deep Vein Thrombosis

100%

80%

60%

40%

20%

Study treatment Arm

Single Arm

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Osimertinib

2017

Completed Phase 4

~1100

0 / 13Eligibility criteria met