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Tyrosine Kinase Inhibitor

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

Phase 1

Recruiting

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

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

Study 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.Check my eligibility

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.See study design

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.

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

Outcome measures can provide a clearer picture of what you can expect from a treatment.

Primary outcome measures

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

Secondary outcome measures

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

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

~1010

0 / 7Eligibility criteria met

Find a Location

Who is running the clinical trial?

AstraZenecaIndustry Sponsor

4,271 Previous Clinical Trials

288,612,416 Total Patients Enrolled

Merck Sharp & Dohme LLCIndustry Sponsor

3,892 Previous Clinical Trials

5,060,866 Total Patients Enrolled

Daiichi SankyoLead Sponsor

392 Previous Clinical Trials

415,946 Total Patients Enrolled

Media Library

Osimertinib (Tyrosine Kinase Inhibitor) Clinical Trial Eligibility Overview. Trial Name: NCT04676477 — Phase 1

Non-Small Cell Lung Cancer Research Study Groups: First-line Dose Expansion: HER3-DXd + osimertinib (Cohort 4a), First-line Dose Expansion: HER3-DXd + osimertinib (Cohort 4b), Dose Escalation: HER3-DXd + osimertinib, Second-line Dose Expansion: HER3-DXd + osimertinib (RCD), Second-line Dose Expansion: HER3-DXd, First-line Dose Expansion: HER3-DXd + osimertinib (Cohort 3; RCD)

Non-Small Cell Lung Cancer Clinical Trial 2023: Osimertinib Highlights & Side Effects. Trial Name: NCT04676477 — Phase 1

Osimertinib (Tyrosine Kinase Inhibitor) 2023 Treatment Timeline for Medical Study. Trial Name: NCT04676477 — Phase 1

Frequently Asked Questions

These questions and answers are submitted by anonymous patients, and have not been verified by our internal team.

What are the possible adverse effects of Osimertinib treatment?

"Considering the limited information available as part of a Phase 1 trial, our team at Power gave osimertinib a score of 1 for safety."

Answered by AI

What is the maximum participant capacity of this medical research?

"For the success of this medical trial, 252 participants must meet predetermined qualifications. Those wishing to participate can find locations such as Massachusetts General Hospital Cancer Center in New york or Memorial Sloan Kettering Cancer Centre located in Fairfax, Virginia."

Answered by AI

Is this investigation actively seeking participants?

"Affirmative. Information posted on clinicaltrials.gov reveals that this research project is actively recruiting participants, which was first reported in June 2021 and the latest update being late November 2022. The study requires 252 individuals from 4 locations to take part."

Answered by AI

Is this experiment an unprecedented endeavor?

"To date, there have been 101 clinical studies with Osimertinib across 51 different nations and 1059 cities. The first of these trials was conducted in 2013 by AstraZeneca, which tested the drug on 603 participants and achieved Phase 1 & 2 approval. Since then, an additional 30 experiments have taken place."

Answered by AI

What outcomes is this research endeavor hoping to demonstrate?

"The primary outcome of this experiment, which is assessed for roughly 47 days after the last dose and up to 18 months following treatment, will measure Dose-Limiting Toxicities (DLT), Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Effects of Special Interest. Secondary outcomes include Disease Control Rate (DCR - a ratio of participants with complete response, partial response or stable disease as per RECIST v1.1.), Time to Response (TTR - time from start of study until first documented response by BICR/Investigator per RECIST v1.1"

Answered by AI

Are there any existing investigations into Osimertinib's efficacy?

"Currently, there are 101 ongoing trials assessing the efficacy of Osimertinib with 17 being at phase 3. While much of the research is based in Uniondale, New york, many other medical institutions across 4702 locations also have studies underway."

Answered by AI

Recent research and studies

clinicaltrials.govStudy

HER3-DXd (Patritumab Deruxtecan; U3-1402) in Combination With Osimertinib in Subjects With Locally Advanced or Metastatic EGFR-mutated Non-Small Cell Lung Cancer

2021. "HER3-DXd (Patritumab Deruxtecan; U3-1402) in Combination With Osimertinib in Subjects With Locally Advanced or Metastatic EGFR-mutated Non-Small Cell Lung Cancer". ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT04676477.

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