Phase 1b Study of Dato-DXd in Combination With Immunotherapy With or Without Carboplatin in Advanced or Metastatic Non-Small Cell Lung Cancer

Advanced or Metastatic NSCLC Clinical Trial

— TROPION-Lung04  

Official title:

A Phase 1b, Multicenter, 2-Part, Open-Label Study of Datopotamab Deruxtecan (Dato-DXd) in Combination With Immunotherapy With or Without Carboplatin in Participants With Advanced or Metastatic Non-Small Cell Lung Cancer (Tropion-Lung04)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04612751
• Other study ID #: D926FC00001
• Secondary ID: 2021-000274-28
• Status: Recruiting
• Phase: Phase 1
• Start date: February 2, 2021
• Est. completion date: January 30, 2026

Study information

• Verified date: May 2024
• Source: AstraZeneca
• Contact: AstraZeneca Clinical Study Information Center
• Phone: 1-877-240-9479
• Email: information.center[@]astrazeneca.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will assess safety, tolerability, and treatment activity of datopotamab deruxtecan (Dato-DXd) in combination with immunotherapy in participants with advanced or metastatic non-small cell lung cancer (NSCLC).

Description:

The primary objective is to assess the safety and tolerability of Dato-DXd in combination with immunotherapy with or without 4 cycles of carboplatin in participants with advanced or metastatic NSCLC. Two dose levels of Dato-DXd will be studied in combination with immunotherapy (durvalumab, AZD2936, MEDI5752, or AZD7789) with or without 4 cycles of carboplatin in 14 study cohorts Each cohort will start with Part 1 (dose escalation or confirmation), where 3 to 9 participants will be assessed for dose-limiting toxicities (DLT) in the first cycle of treatment. if the DLT incidence rate meets the criteria based on the modified toxicity probability interval-2 (mTPI-2), then Part 2 (dose expansion) may be opened.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 321
• Est. completion date: January 30, 2026
• Est. primary completion date: January 30, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Participant =18 years old on the day of signing the ICF (local regulatory requirement to consent should be followed).
• Histologically or cytologically confirmed diagnosis of advanced or metastatic NSCLC, without EGFR or ALK genomic alterations (testing not required for participants with documented squamous histology) and no known genomic alterations in other actionable driver kinases with approved therapies. Participants whose tumors harbor KRAS mutations are eligible for this study.
• For Cohorts 1 to 4, participants must be treatment-naïve or have received and radiologically progressed after only 1 prior line of systemic chemotherapy, without concomitant immune checkpoint inhibitors for advanced or metastatic NSCLC. For Cohorts 5 to 11 and 14, participants must be treatment-naïve for advanced or metastatic NSCLC. For Cohorts 12 to 13, participants must be CPI acquired resistant after 1 or 2 prior lines of systemic therapy for advanced or metastatic NSCLC, of which 1 should have contained an approved anti-PD-1/PD L1
• Willing and able to undergo a mandatory tumor biopsy. A tumor biopsy that was recently collected (within 3 months of screening) after completion of the most recent anticancer treatment regimen may be substituted for the biopsy collected during screening. For Cohorts 12 and 13, a tumor sample taken =24 months prior to screening is acceptable.
• Has measurable disease per RECIST1.1 within 28 days prior to Cycle 1 Day 1
• Eastern Co-operative Oncology Group (ECOG) performance status of 0 or 1 at screening
• Has adequate bone marrow reserve and organ function at baseline within 7 days prior to Cycle 1 day 1
• For Cohorts 5 to 14 only: Documented IHC PD-L1 expression per analytically validated Ventana PD-L1 (SP263) IHC assay, 22C3 PharmDx assay, or 28-8 PharmDx assay

Exclusion Criteria:

• Active or prior documented autoimmune or inflammatory disorders
• Uncontrolled or significant cardiac disease
• History of another primary malignancy with exceptions
• active or uncontrolled hepatitis B or C virus or uncontrolled HIV infection
• spinal cord compression or clinically active CNS metastases
• History of (non-infectious) ILD/pneumonitis that required steroids
• Clinically severe pulmonary compromise resulting from intercurrent pulmonary illness
• Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals
• Clinically significant corneal disease

Related Conditions & MeSH terms

• Advanced or Metastatic NSCLC
• Carcinoma, Non-Small-Cell Lung

Intervention

Drug:
• Datopotamab deruxtecan
Intravenous infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle
• Durvalumab
Intravenous infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle
• Carboplatin
Intravenous infusion Q3W on Day 1 or Day 2 of each 21-day cycle
• AZD2936
Intravenous infusion prior to Dato-DXd
• MEDI5752
Intravenous infusion prior to Dato-DXd
• AZD7789
Intravenous infusion prior to Dato-DXd

Locations

Country	Name	City	State
Belgium	Research Site	Hasselt
Belgium	Research Site	Mechelen
Belgium	Research Site	Roeselare
France	Research Site	Paris Cedex 05
Italy	Research Site	Aviano
Italy	Research Site	Meldola
Italy	Research Site	Milano
Italy	Research Site	Orbassano
Italy	Research Site	Roma
Japan	Research Site	Koto-ku
Japan	Research Site	Sunto-gun
Japan	Research Site	Yokohama-shi
Korea, Republic of	Research Site	Busan
Korea, Republic of	Research Site	Cheongiu
Korea, Republic of	Research Site	Hwasun-gun
Korea, Republic of	Research Site	JinJoo
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Suwon
Korea, Republic of	Research Site	Suwon-si
Poland	Research Site	Gdansk
Poland	Research Site	Lódz
Poland	Research Site	Lódz
Poland	Research Site	Poland
Poland	Research Site	Warszawa
Spain	Research Site	A Coruña
Spain	Research Site	Badalona
Spain	Research Site	Barcelona
Spain	Research Site	Barcelona
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Pozuelo de Alarcon
Spain	Research Site	Sevilla
Taiwan	Research Site	Changhua
Taiwan	Research Site	Hsinchu
Taiwan	Research Site	Kaohsiung City
Taiwan	Research Site	Taichung
Taiwan	Research Site	Tainan
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei City
Taiwan	Research Site	Taoyuan
Turkey	Research Site	Adana
Turkey	Research Site	Ankara
Turkey	Research Site	Ankara
Turkey	Research Site	Ankara
Turkey	Research Site	Istanbul
Turkey	Research Site	Izmir
Turkey	Research Site	Konya
Turkey	Research Site	Malatya
United States	Research Site	Chicago	Illinois
United States	Research Site	Cleveland	Ohio
United States	Research Site	Dallas	Texas
United States	Research Site	Detroit	Michigan
United States	Research Site	Duarte	California
United States	Research Site	Fairfax	Virginia
United States	Research Site	Hackensack	New Jersey
United States	Research Site	Hershey	Pennsylvania
United States	Research Site	Houston	Texas
United States	Research Site	La Jolla	California
United States	Research Site	Lebanon	New Hampshire
United States	Research Site	Nashville	Tennessee
United States	Research Site	New York	New York
United States	Research Site	Philadelphia	Pennsylvania
United States	Research Site	Saint Louis	Missouri
United States	Research Site	San Antonio	Texas
United States	Research Site	Santa Ana	California
United States	Research Site	Tyrone	Georgia

Sponsors (2)

Lead Sponsor	Collaborator
AstraZeneca	Daiichi Sankyo

Countries where clinical trial is conducted

United States,  Belgium,  France,  Italy,  Japan,  Korea, Republic of,  Poland,  Spain,  Taiwan,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with DLTs; TEAEs and other safety parameters during the study.	DLTs, TEAEs, SAEs, AESIs, ECOG PS, vital sign measurements, standard clinical laboratory parameters (hematology, clinical chemistry, and urinalysis), ECG parameters, ECHO/MUGA scan findings, and ophthalmologic findings	DLTs: within first cycle (21 days); TEAEs and other safety parameters: when all participants have either discontinued the study or the last participant enrolled in the study has completed at least 9 months of follow-up (approximately 55 months)
Secondary	ORR as assessed by investigator per RECIST Version 1.1	ORR is defined as the proportion of participants with measurable disease at baseline who achieved a BOR of confirmed CR or confirmed PR.	At the time of the final analysis (when all participants have either discontinued the study or the last participant enrolled in the study has completed at least 9 months of follow-up, approximately 55 months).
Secondary	Duration of Response as assessed by investigator per RECIST version 1.1	Duration of Response is defined as the time from the date of the first documentation of objective response (confirmed CR or confirmed PR) to the date of the first documentation of objective PD, or death due to any cause, whichever occurs first.	At the time of the final analysis (when all participants have either discontinued the study or the last participant enrolled in the study has completed at least 9 months of follow-up, approximately 55 months).
Secondary	Disease Control Rate as assessed by the investigator per RECIST version 1.1	Disease Control Rate is defined as the proportion of participants who achieved a Best Overall Response of confirmed complete response, confirmed partial response, or stable disease.	At the time of the final analysis (when all participants have either discontinued the study or the last participant enrolled in the study has completed at least 9 months of follow-up, approximately 55 months).
Secondary	Progression-free Survival as assessed by the investigator per RECIST v1.1	Progression-free Survival is defined as the time interval from the date of the start of study treatment to the earlier of the dates of the first documentation of objective PD or death due to any cause, whichever occurs first	At the time of the final analysis (when all participants have either discontinued the study or the last participant enrolled in the study has completed at least 9 months of follow-up, approximately 55 months).
Secondary	Time to Response as assessed by investigator per RECIST Version 1.1	Time to Response is defined as the time from the date of the start of study treatment to the date of the first documentation of objective response (confirmed complete response or confirmed partial response)	At the time of the final analysis (when all participants have either discontinued the study or the last participant enrolled in the study has completed at least 9 months of follow-up, approximately 55 months).
Secondary	Best percentage change in the Sum of Diameters of measurable tumors	The best percentage change in the Sum of Diameters of measurable tumors is defined as the percentage change in the smallest Sum of Diameters from all postbaseline tumor assessments, taking as reference the baseline Sum of Diameters.	At the time of the final analysis (when all participants have either discontinued the study or the last participant enrolled in the study has completed at least 9 months of follow-up, approximately 55 months).
Secondary	Overall Survival	Overall Survival is defined as the time from the date of the start of study treatment to the date of death due to any cause	At the time of the final analysis (when all participants have either discontinued the study or the last participant enrolled in the study has completed at least 9 months of follow-up, approximately 55 months).
Secondary	Pharmacokinetic Parameter Maximum Plasma/Serum Concentration (Cmax) of Dato-DXd, Total anti-TROP2 antibody, and MAAA-1181a. Serum concentrations of durvalumab and MEDI5752, AZD2936, MEDI5752 and AZD7789.	Cmax = Maximum concentration	At the time of the final analysis (when all participants have either discontinued the study or the last participant enrolled in the study has completed at least 9 months of follow-up, approximately 55 months).
Secondary	Pharmacokinetic Parameter Time to Maximum Plasma/Serum Concentration (Tmax) of Dato-DXd, Total anti-TROP2 antibody, and MAAA-1181a.	Tmax = time to reach maximum concentration.	At the time of the final analysis (when all participants have either discontinued the study or the last participant enrolled in the study has completed at least 9 months of follow-up, approximately 55 months).
Secondary	Pharmacokinetic Parameter Area Under the Plasma Concentration-Time Curve (AUC) of Dato-DXd, Total anti-TROP2 antibody, and MAAA-1181a.	Area under the plasma concentration-time curve up to last quantifiable time (AUClast) and area under the plasma concentration-time curve during dosing interval (AUCtau) will be assessed.	At the time of the final analysis (when all participants have either discontinued the study or the last participant enrolled in the study has completed at least 9 months of follow-up, approximately 55 months).
Secondary	Prevalence of Dato-Dxd, durvalumab, AZD2936, MEDI5752 and AZD7789 ADA	ADA prevalence is defined as the proportion of all participants having ADA at any point in time (including pre-existing ADA at baseline and treatment-emergent ADA)	At the time of the final analysis (when all participants have either discontinued the study or the last participant enrolled in the study has completed at least 9 months of follow-up, approximately 55 months).
Secondary	Incidence of Dato-DXd, durvalumab, AZD2936, MEDI5752 and AZD7789 ADA	ADA incidence is defined as the proportion of participants having treatment-emergent ADA during the study period	At the time of the final analysis (when all participants have either discontinued the study or the last participant enrolled in the study has completed at least 9 months of follow-up, approximately 55 months).