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

NCT04612751 | Active Not Recruiting Phase 1 FDA Drug

• 3 other identifiers: D926FC000012023-505992-54-002021-000274-28
• Study Type: interventional
• Target: 155
• Locations: 8 countries
• Sites: 42

Brief Summary

This study will assess safety, tolerability, and treatment activity of datopotamab deruxtecan (Dato-DXd) in combination with immunotherapy with or without carboplatin in participants with advanced or metastatic non-small cell lung cancer (NSCLC).

Conditions

Advanced or Metastatic NSCLC

Keywords

Advanced or Metastatic NSCLC; Datopotamab deruxtecan (Dato-DXd); DS-1062a; Durvalumab; AZD2936; MEDI5752; AZD7789

Outcome Measures

Primary Outcomes (1)

• 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 60 months)

Secondary Outcomes (12)

• ORR as assessed by investigator per RECIST Version 1.1

  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 60 months).

• Duration of Response as assessed by investigator per RECIST version 1.1

  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 60 months).

• Disease Control Rate as assessed by the investigator per RECIST version 1.1

  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 60 months).

• Progression-free Survival as assessed by the investigator per RECIST v1.1

  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 60 months).

• Time to Response as assessed by investigator per RECIST Version 1.1

  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 60 months).

Study Arms (15)

Cohort 1

EXPERIMENTAL

Datopotamab deruxtecan (Dato-DXd) + Durvalumab in NSCLC participants who are either treatment-naïve or have received only 1 prior line of systemic chemotherapy without concomitant ICI therapy

Drug: Datopotamab deruxtecan; Drug: Durvalumab

Cohort 2

EXPERIMENTAL

Datopotamab deruxtecan (Dato-DXd) + Durvalumab in NSCLC participants who are either treatment-naïve or have received only 1 prior line of systemic chemotherapy without concomitant ICI therapy

Drug: Datopotamab deruxtecan; Drug: Durvalumab

Cohort 3

EXPERIMENTAL

Datopotamab deruxtecan (Dato-DXd) + Durvalumab + Carboplatin in NSCLC participants who are either treatment-naïve or have received only 1 prior line of systemic chemotherapy without concomitant ICI therapy

Drug: Datopotamab deruxtecan; Drug: Durvalumab; Drug: Carboplatin

Cohort 4

EXPERIMENTAL

Datopotamab deruxtecan (Dato-DXd) + Durvalumab + Carboplatin in NSCLC participants who are either treatment-naïve or have received only 1 prior line of systemic chemotherapy without concomitant ICI therapy

Drug: Datopotamab deruxtecan; Drug: Durvalumab; Drug: Carboplatin

Cohort 5

EXPERIMENTAL

Datopotamab deruxtecan (Dato-DXd) + AZD2936 in participants with treatment-naïve NSCLC

Drug: Datopotamab deruxtecan; Drug: AZD2936

Cohort 6

EXPERIMENTAL

Datopotamab deruxtecan (Dato-DXd) + AZD2936 in participants with treatment-naïve NSCLC

Drug: Datopotamab deruxtecan; Drug: AZD2936

Cohort 7

EXPERIMENTAL

Datopotamab deruxtecan (Dato-DXd) + AZD2936 + Carboplatin in participants with treatment-naïve NSCLC

Drug: Datopotamab deruxtecan; Drug: Carboplatin; Drug: AZD2936

Cohort 8

EXPERIMENTAL

Datopotamab deruxtecan (Dato-DXd) + AZD2936 + Carboplatin in participants with treatment-naïve NSCLC

Drug: Datopotamab deruxtecan; Drug: Carboplatin; Drug: AZD2936

Cohort 9

EXPERIMENTAL

Datopotamab deruxtecan (Dato-DXd) + MEDI5752 + Carboplatin in participants with treatment-naïve NSCLC

Drug: Datopotamab deruxtecan; Drug: Carboplatin; Drug: MEDI5752

Cohort 10

EXPERIMENTAL

Datopotamab deruxtecan (Dato-DXd) + MEDI5752 + Carboplatin in participants with treatment-naïve NSCLC

Drug: Datopotamab deruxtecan; Drug: Carboplatin; Drug: MEDI5752

Cohort 11

EXPERIMENTAL

Datopotamab deruxtecan (Dato-DXd) + MEDI5752 in participants with treatment-naïve NSCLC

Drug: Datopotamab deruxtecan; Drug: MEDI5752

Cohort 12

EXPERIMENTAL

Datopotamab deruxtecan (Dato-DXd) + AZD7789 in participants with CPI acquired resistant NSCLC

Drug: Datopotamab deruxtecan; Drug: AZD7789

Cohort 13

EXPERIMENTAL

Datopotamab deruxtecan (Dato-DXd) + AZD7789 in participants with CPI acquired resistant NSCLC

Drug: Datopotamab deruxtecan; Drug: AZD7789

Cohort 14

EXPERIMENTAL

Datopotamab deruxtecan (Dato-DXd) + AZD7789 in participants with treatment-naïve NSCLC

Drug: Datopotamab deruxtecan; Drug: AZD7789

Cohort 4A

EXPERIMENTAL

Datopotamab deruxtecan (Dato-DXd) + Durvalumab + carboplatin in participants with treatment-naïve NSCLC

Drug: Datopotamab deruxtecan; Drug: Durvalumab; Drug: Carboplatin

Interventions

Datopotamab deruxtecan DRUG

Intravenous infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle

Also known as: Dato-DXd

Cohort 1; Cohort 10; Cohort 11; Cohort 12; Cohort 13; Cohort 14; Cohort 2; Cohort 3; Cohort 4; Cohort 4A; Cohort 5; Cohort 6; Cohort 7; Cohort 8; Cohort 9

Durvalumab DRUG

Intravenous infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle

Also known as: Imfinzi

Cohort 1; Cohort 2; Cohort 3; Cohort 4; Cohort 4A

Carboplatin DRUG

Intravenous infusion Q3W on Day 1 or Day 2 of each 21-day cycle

Cohort 10; Cohort 3; Cohort 4; Cohort 4A; Cohort 7; Cohort 8; Cohort 9

AZD2936 DRUG

Intravenous infusion prior to Dato-DXd every 3 weeks (Q3W) on Day 1 prior to Dato-Dxd of each 21-day cycle

Also known as: rilvegostomig

Cohort 5; Cohort 6; Cohort 7; Cohort 8

MEDI5752 DRUG

Intravenous infusion prior to Dato-DXd every 3 weeks (Q3W) on Day 1 prior to Dato-Dxd of each 21-day cycle

Also known as: volrustomig

Cohort 10; Cohort 11; Cohort 9

AZD7789 DRUG

Intravenous infusion prior to Dato-DXd every 3 weeks (Q3W) on Day 1 prior to Dato-Dxd of each 21-day cycle

Also known as: sabestomig

Cohort 12; Cohort 13; Cohort 14

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 4a, 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. Cohort 4a will enroll participants whose tumors have squamous histology only; Cohorts 5 Part 2A and Part 2B as well as Cohorts 12 and 13 will enroll participants whose tumors have non-squamous histology only.
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• AstraZeneca: lead
• Daiichi Sankyo: collaborator

Study Sites (42)

Research Site

La Jolla, California, 92093, United States

Location

Research Site

Santa Ana, California, 92705, United States

Location

Research Site

St Louis, Missouri, 63110, United States

Location

Research Site

Hackensack, New Jersey, 07601, United States

Location

Research Site

Cleveland, Ohio, 44106, United States

Location

Research Site

Philadelphia, Pennsylvania, 19111, United States

Location

Research Site

Dallas, Texas, 75230, United States

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Research Site

Houston, Texas, 77030, United States

Location

Research Site

San Antonio, Texas, 78229, United States

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Research Site

Fairfax, Virginia, 22031, United States

Location

Research Site

Hasselt, 3500, Belgium

Location

Research Site

Roeselare, 8800, Belgium

Location

Research Site

Aviano, 33081, Italy

Location

Research Site

Meldola, 47014, Italy

Location

Research Site

Orbassano, 10043, Italy

Location

Research Site

Roma, 00144, Italy

Location

Research Site

Kōtoku, 135-8550, Japan

Location

Research Site

Sunto-gun, 411-8777, Japan

Location

Research Site

Yokohama, 241-8515, Japan

Location

Research Site

Gdansk, 80-952, Poland

Location

Research Site

Lodz, 93-338, Poland

Location

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Lublin, 20-090, Poland

Location

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Warsaw, 02-781, Poland

Location

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A Coruña, 15005, Spain

Location

Research Site

Badalona, 08916, Spain

Location

Research Site

Barcelona, 8036, Spain

Location

Research Site

Madrid, 28034, Spain

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Madrid, 28046, Spain

Location

Research Site

Madrid, 28050, Spain

Location

Research Site

Seville, 41015, Spain

Location

Research Site

Hsinchu, 300, Taiwan

Location

Research Site

Taichung, 40705, Taiwan

Location

Research Site

Tainan, 704, Taiwan

Location

Research Site

Taipei, 100, Taiwan

Location

Research Site

Taipei, 110, Taiwan

Location

Research Site

Taipei, 11217, Taiwan

Location

Research Site

Taoyuan District, 00333, Taiwan

Location

Research Site

Adana, 01060, Turkey (Türkiye)

Location

Research Site

Ankara, 06800, Turkey (Türkiye)

Location

Research Site

Ankara, 6200, Turkey (Türkiye)

Location

Research Site

Istanbul, 34010, Turkey (Türkiye)

Location

Research Site

Izmir, 35330, Turkey (Türkiye)

Location

Related Links

• Lung Cancer Study Locator details (for US)

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

durvalumab; Carboplatin

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Dose escalation and dose expansion model

Study Record Dates

• First Submitted: October 21, 2020
• First Posted: November 3, 2020
• Study Start: February 2, 2021
• Primary Completion: April 30, 2026
• Study Completion: April 30, 2026
• Last Updated: December 18, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure

Locations

TU (5); TW (7); JP (3); ES (7); BE (2); US (10); IT (4); PL (4)