RECRUITING

Phase Ib Study of the Safety of T-DXd and Immunotherapy Agents With and Without Chemotherapy in Advanced or Metastatic HER2+, Non-squamous NSCLC

Conditions

Locally Advanced or Metastatic Non-Small Cell Lung Cancer HER2+HER2 expression DS-8201a T-DXd Trastuzumab Deruxtecan Volrustomig (MEDI5752)Antibody - drug conjugate bispecific antibody Volrustomig Rilvegostomig Carboplatin First line Locally advanced and unresectable non-squamous NSCLC Metastatic non-squamous NSCLC Non-small cell lung cancer

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

DESTINY-Lung03 will investigate the safety and tolerability of trastuzumab deruxtecan in combination with Immunotherapy Agents with and without chemotherapy in patients with HER2 over-expressing non-small cell lung cancer. The efficacy will be also analyzed as a secondary endpoint.

Official Title

A Phase Ib Multicenter, Open-label Study to Evaluate the Safety and Tolerability of Trastuzumab Deruxtecan (T-DXd) and Immunotherapy Agents With and Without Chemotherapy Agents in First-line Treatment of Patients With Advanced or Metastatic Non-squamous Non-small Cell Lung Cancer (NSCLC) and Human Epidermal Growth Factor Receptor 2 (HER2) Overexpression (OE) (DESTINY-Lung03)

Quick Facts

Study Start:2021-03-09

Study Completion:2025-12-23

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT04686305

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* Histologically documented unresectable locally advanced/metastatic non-squamous NSCLC * Part 1: Progression after 1 or 2 lines of systemic therapy for recurrent or metastatic setting. * Part 3 and 4: Patients must have tumors that do not harbor known genomic alterations or actionable driver kinases, for which approved therapies are available are allowed. * Part 3 and 4: Patient must be treatment-naïve for advanced or metastatic NSCLC. Patients who have received prior adjuvant, or neoadjuvant chemotherapy, or definitive chemoradiation for advanced disease are eligible, provided that progression has occurred \> 6 months from end of last therapy * HER2overexpression status as determined by central review of tumor tissue * WHO / ECOG performance status of 0 or 1 * Measurable target disease assessed by the investigator using RECIST 1.1 * Has protocol defined adequate organ and bone marrow function * Part 3 and part 4: Minimum body weight of 35 kg.	* HER2 mutation if previously known * Has a history of (non-infectious) ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening * Lung-specific intercurrent clinically significant illnesses including, but not limited to, any underlying pulmonary disorder and prior pneumonectomy * Active primary immunodeficiency known HIV infection, or active chronic and resolved hepatitis B (positive hepatitis B virus surface antigen \[HBsAg+ve\] or hepatitis B virus core antibody (anti-HBc +ve) regardless of HBV DNA level)) or hepatitis C infection. Patients positive for HCV antibody are eligible only if polymerase chain reaction is negative for HCV RNA. Patients should be tested for HIV prior to treatment assignment if required by local regulations or IRB/EC * Active infection including tuberculosis and uncontrolled infection requiring IV antibiotics, antivirals, or antifungals * Spinal cord compression or clinically active central nervous system metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms * Medical history of myocardial infarction within 6 months before treatment assignment, symptomatic CHF (New York Heart Association Class II to IV), clinically important cardiac arrhythmias, or a recent (\< 6 months) cardiovascular event including stroke * For Part 3 and Part 4: Cardiomyopathy of any etiology, symptomatic CHF (as defined by New York Heart Association Class \> II), unstable angina pectoris, history of MI within the past 12 months, or cardiac arrhythmia are to be excluded. Patients with troponin levels above ULN at screening (as defined by the manufacturer), and without any myocardial related symptoms, should have a cardiologic consultation before treatment assignment to rule out acute cardiopulmonary events. * Ascites or pericardial effusion that requires drainage, peritoneal shunt, Pleuroperitoneal shunt or CART (Concentrated Ascites Reinfusion Therapy) * For Part 3 and Part 4: Active non-infectious skin disease (including any grade rash, urticarial, dermatitis, ulceration, or psoriasis) requiring systemic treatment, active or prior documented autoimmune or inflammatory disorders requiring chronic treatment with steroids or other immunosuppressive treatment. * Unresolved toxicities not yet resolved to Grade ≤ 1 or baseline from previous anticancer therapy OR prior discontinuation of any planned study therapy due to toxicity. * must not have any medical contraindication to platinum-based chemotherapy. * Part 3 and 4 patients must not have had prior exposure to anti-PD-1, anti-PD-L1, anti-CTLA-4, anti-TIGIT or any other experimental immunotherapy in any setting. * For Part 3 and Part 4: History of substance abuse or any other medical or psychological conditions that may, in the opinion of the Investigator, interfere with the subject's participation in the clinical study or evaluation of the clinical study results * For Part 3 and Part 4: History of thromboembolic events within 3 months before the first dose of IP (limited to pulmonary embolism, deep vein thrombosis, or cerebral venous sinus thrombosis).

Inclusion Criteria

Exclusion Criteria

* Histologically documented unresectable locally advanced/metastatic non-squamous NSCLC
* Part 1: Progression after 1 or 2 lines of systemic therapy for recurrent or metastatic setting.
* Part 3 and 4: Patients must have tumors that do not harbor known genomic alterations or actionable driver kinases, for which approved therapies are available are allowed.
* Part 3 and 4: Patient must be treatment-naïve for advanced or metastatic NSCLC. Patients who have received prior adjuvant, or neoadjuvant chemotherapy, or definitive chemoradiation for advanced disease are eligible, provided that progression has occurred \> 6 months from end of last therapy
* HER2overexpression status as determined by central review of tumor tissue
* WHO / ECOG performance status of 0 or 1
* Measurable target disease assessed by the investigator using RECIST 1.1
* Has protocol defined adequate organ and bone marrow function
* Part 3 and part 4: Minimum body weight of 35 kg.

* HER2 mutation if previously known
* Has a history of (non-infectious) ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening
* Lung-specific intercurrent clinically significant illnesses including, but not limited to, any underlying pulmonary disorder and prior pneumonectomy
* Active primary immunodeficiency known HIV infection, or active chronic and resolved hepatitis B (positive hepatitis B virus surface antigen \[HBsAg+ve\] or hepatitis B virus core antibody (anti-HBc +ve) regardless of HBV DNA level)) or hepatitis C infection. Patients positive for HCV antibody are eligible only if polymerase chain reaction is negative for HCV RNA. Patients should be tested for HIV prior to treatment assignment if required by local regulations or IRB/EC
* Active infection including tuberculosis and uncontrolled infection requiring IV antibiotics, antivirals, or antifungals
* Spinal cord compression or clinically active central nervous system metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms
* Medical history of myocardial infarction within 6 months before treatment assignment, symptomatic CHF (New York Heart Association Class II to IV), clinically important cardiac arrhythmias, or a recent (\< 6 months) cardiovascular event including stroke
* For Part 3 and Part 4: Cardiomyopathy of any etiology, symptomatic CHF (as defined by New York Heart Association Class \> II), unstable angina pectoris, history of MI within the past 12 months, or cardiac arrhythmia are to be excluded. Patients with troponin levels above ULN at screening (as defined by the manufacturer), and without any myocardial related symptoms, should have a cardiologic consultation before treatment assignment to rule out acute cardiopulmonary events.
* Ascites or pericardial effusion that requires drainage, peritoneal shunt, Pleuroperitoneal shunt or CART (Concentrated Ascites Reinfusion Therapy)
* For Part 3 and Part 4: Active non-infectious skin disease (including any grade rash, urticarial, dermatitis, ulceration, or psoriasis) requiring systemic treatment, active or prior documented autoimmune or inflammatory disorders requiring chronic treatment with steroids or other immunosuppressive treatment.
* Unresolved toxicities not yet resolved to Grade ≤ 1 or baseline from previous anticancer therapy OR prior discontinuation of any planned study therapy due to toxicity.
* must not have any medical contraindication to platinum-based chemotherapy.
* Part 3 and 4 patients must not have had prior exposure to anti-PD-1, anti-PD-L1, anti-CTLA-4, anti-TIGIT or any other experimental immunotherapy in any setting.
* For Part 3 and Part 4: History of substance abuse or any other medical or psychological conditions that may, in the opinion of the Investigator, interfere with the subject's participation in the clinical study or evaluation of the clinical study results
* For Part 3 and Part 4: History of thromboembolic events within 3 months before the first dose of IP (limited to pulmonary embolism, deep vein thrombosis, or cerebral venous sinus thrombosis).

Contacts and Locations

Study Contact

AstraZeneca Clinical Study Information Center

CONTACT

1-877-240-9479

information.center@astrazeneca.com

AstraZeneca Lung Cancer Study Locator Service

CONTACT

1-884-432-3892

az-lcsl@careboxhealth.com

Study Locations (Sites)

Research Site

Duarte, California, 91010

United States

Research Site

Newport Beach, California, 92663

United States

Research Site

Orange, California, 92868

United States

Research Site

Santa Rosa, California, 95403

United States

Research Site

Westwood, Kansas, 66205

United States

Research Site

Baltimore, Maryland, 21287

United States

Research Site

Detroit, Michigan, 48201

United States

Research Site

Bronx, New York, 10461

United States

Research Site

Buffalo, New York, 14263

United States

Research Site

New York, New York, 10029

United States

Research Site

Houston, Texas, 77030

United States

Research Site

Fairfax, Virginia, 22031

United States

Research Site

Tacoma, Washington, 98405

United States

Collaborators and Investigators

Sponsor: AstraZeneca

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2021-03-09

Study Completion Date2025-12-23

Study Record Updates

Study Start Date2021-03-09

Study Completion Date2025-12-23

Terms related to this study

Keywords Provided by Researchers

HER2+
HER2 expression
DS-8201a
T-DXd
Trastuzumab Deruxtecan
Volrustomig (MEDI5752)
Antibody - drug conjugate
bispecific antibody
Volrustomig
Rilvegostomig
Carboplatin
First line
Locally advanced and unresectable non-squamous NSCLC
Metastatic non-squamous NSCLC
Non-small cell lung cancer

Additional Relevant MeSH Terms

Locally Advanced or Metastatic Non-Small Cell Lung Cancer