Phase III, Open-label Study of First-line Osimertinib With or Without Datopotamab Deruxtecan for EGFRm Locally Advanced or Metastatic Non-small Cell Lung Cancer

Last updated: March 12, 2025
Sponsor: AstraZeneca
Overall Status: Active - Recruiting

Phase

3

Condition

Non-small Cell Lung Cancer

Treatment

Osimertinib

Datopotamab Deruxtecan

Clinical Study ID

NCT06350097
D516NC00001
  • Ages > 18
  • All Genders

Study Summary

The purpose of this study is to evaluate efficacy and safety of osimertinib (tablet) in combination with Datopotamab Deruxtecan (i.v. infusion) compared with osimertinib (tablet) monotherapy as a first-line therapy in participants with locally advanced or metastatic EGFRm (Ex19del and/or L858R) NSCLC.

Study details include:

  1. The study duration will be event-driven, with an estimated duration of approximately 9 years.

  2. Participants may receive study treatment until disease progression, unacceptable toxicity, or other specific discontinuation criteria are met.

  3. The visit frequency will be every 3 weeks during the treatment period.

Note: Participants on osimertinib treatment (osimertinib only arm or who have discontinued Datopotamab Deruxtecan while are still receiving osimertinib) are required to attend visits to perform assessments every 6 weeks from Cycle 7 until Cycle 17 and then visits every 12 weeks until disease progression, IP discontinuation or primary PFS DCO. Participants who are receiving osimertinib + Datopotamab Deruxtecan are still required to attend visit to perform assessment every 3 weeks (q3w) per SoA.

Eligibility Criteria

Inclusion

Inclusion Criteria:

Age

  1. Participant must be ≥ 18 years; Participant from Japan must be ≥ 20 years, at thetime of signing the ICF. Type of Participant and Disease Characteristics

  2. Histologically or cytologically documented nonsquamous NSCLC.

  3. Stage IIIB or IIIC or Stage IV metastatic NSCLC or recurrent NSCLC (based on theAmerican Joint Committee on Cancer Edition 8) not amenable to curative surgery ordefinitive chemoradiation at the time of randomisation.

  4. Participants must not have received prior EGFR TKIs or other systemic therapy forStage IIIB, IIIC or IV NSCLC.

  5. The tumour harbors 1 of the 2 common EGFR mutations known to be associated withEGFR-TKI sensitivity (Ex19del or L858R), either alone or in combination with otherEGFR mutations.

  6. For participants enrolled in randomisation period, mandatory provision of anunstained, archival tumour tissue sample in a quantity sufficient to allow forcentral confirmation of the EGFR mutation status.

  7. WHO performance status of 0 or 1.

  8. At least one lesion not previously irradiated that qualifies as a RECIST 1.1 TL atbaseline and can be accurately measured at baseline as ≥10 mm in the longestdiameter (except lymph nodes, which must have short axis ≥15 mm) with CT or MRI andis suitable for accurate repeated measurements.

  9. Adequate bone marrow reserve and organ function within 7 days before the first doseof study intervention . Sex and Contraceptive/Barrier Requirements

  10. Male and female Contraceptive use by males or females should be consistent withlocal regulations regarding the methods of contraception for those participating inclinical studies. Other Inclusion Criteria

  11. All races, gender and ethnic groups are eligible for this study.

Exclusion

Exclusion Criteria:

Medical Conditions

  1. As judged by the investigator, any evidence of diseases (such as severe oruncontrolled systemic diseases, including active bleeding diseases, psychiatricillness/social situations), history of allogenic organ transplant, and/or substanceabuse which, in the investigator's opinion, makes it undesirable for the participantto participate in the study or that would jeopardise compliance with the protocol.

  2. Refractory nausea and vomiting, chronic gastrointestinal disease, inability toswallow the formulated product, or previous significant bowel resection that wouldpreclude adequate absorption, distribution, metabolism, or excretion of osimertinib.

  3. History of another primary malignancy.

  4. Spinal cord compression and unstable brain metastases.

  5. Clinically significant corneal disease.

  6. Has active or uncontrolled hepatitis B or C virus infection.

  7. Known HIV infection that is not well controlled.

  8. Uncontrolled infection requiring i.v. antibiotics, antivirals or antifungals;suspected infections (eg, prodromal symptoms); or inability to rule out infections (participants with localised fungal infections of skin or nails are eligible).

  9. Resting ECG with clinically abnormal findings.

  10. Uncontrolled or significant cardiac disease.

  11. Past medical history of ILD, drug-induced ILD, radiation pneumonitis which requiredsteroid treatment, or any evidence of clinically active ILD.

  12. Has severe pulmonary function compromise. Prior/Concomitant Therapy

  13. Prior exposure to any agent including an ADC containing a chemotherapeutic agenttargeting topoisomerase I, TROP2-targeted therapy. Prior/Concurrent Clinical Study Experience

  14. Participants with a known history of severe hypersensitivity reactions to eitherDato-DXd and osimertinib or any excipients of Dato DXd and osimertinib or drugs witha similar chemical structure or class to DXd and osimertinib.

Study Design

Total Participants: 582
Treatment Group(s): 2
Primary Treatment: Osimertinib
Phase: 3
Study Start date:
April 29, 2024
Estimated Completion Date:
May 25, 2032

Study Description

This is a global Phase III, open-label, randomised, multicentre study assessing the efficacy and safety of osimertinib in combination with Datopotamab Deruxtecan compared with osimertinib in participants with locally advanced or metastatic EGFRm (Ex19del and/or L858R) NSCLC who have not received any prior therapy for advanced disease.

Connect with a study center

  • Research Site

    Clayton, 3168
    Australia

    Active - Recruiting

  • Research Site

    Kogarah, 2217
    Australia

    Active - Recruiting

  • Research Site

    South Brisbane, 4101
    Australia

    Site Not Available

  • Research Site

    Westmead, 2145
    Australia

    Active - Recruiting

  • Research Site

    Barretos, 14784-400
    Brazil

    Active - Recruiting

  • Research Site

    Natal, 59075-740
    Brazil

    Site Not Available

  • Research Site

    Porto Alegre, 91350-200
    Brazil

    Site Not Available

  • Research Site

    Salvador, 41253-190
    Brazil

    Site Not Available

  • Research Site

    Sao Paulo, 01246-000
    Brazil

    Site Not Available

  • Research Site

    Edmonton, Alberta T6G 1Z2
    Canada

    Site Not Available

  • Research Site

    Montreal, Quebec H4A 3J1
    Canada

    Site Not Available

  • Research Site

    Beijing, 100034
    China

    Site Not Available

  • Research Site

    Changchun, 130000
    China

    Active - Recruiting

  • Research Site

    Changsha, 410013
    China

    Site Not Available

  • Research Site

    Chengdu, 610072
    China

    Site Not Available

  • Research Site

    Chongqing, 400030
    China

    Active - Recruiting

  • Research Site

    Guangzhou, 510100
    China

    Active - Recruiting

  • Research Site

    Hangzhou, 310006
    China

    Site Not Available

  • Research Site

    Hankou,Wuhan, 430022
    China

    Site Not Available

  • Research Site

    Harbin, 150049
    China

    Site Not Available

  • Research Site

    Hefei, 230031
    China

    Site Not Available

  • Research Site

    Jinan, 250117
    China

    Active - Recruiting

  • Research Site

    Kunming, 650118
    China

    Active - Recruiting

  • Research Site

    Linhai, 318000
    China

    Active - Recruiting

  • Research Site

    Ningbo, 315010
    China

    Active - Recruiting

  • Research Site

    Shanghai, 200433
    China

    Site Not Available

  • Research Site

    Shenyang, 110004
    China

    Site Not Available

  • Research Site

    Wenzhou, 325000
    China

    Active - Recruiting

  • Research Site

    Wuhan, 430030
    China

    Active - Recruiting

  • Research Site

    Xi'an, 710061
    China

    Active - Recruiting

  • Research Site

    Xuzhou, 221000
    China

    Active - Recruiting

  • Research Site

    Yangzhou, 225001
    China

    Active - Recruiting

  • Research Site

    Zhengzhou, 450008
    China

    Active - Recruiting

  • Research Site

    Zhengzhou City, 450000
    China

    Site Not Available

  • Research Site

    Berlin, 13125
    Germany

    Site Not Available

  • Research Site

    Erfurt, 99089
    Germany

    Site Not Available

  • Research Site

    Frankfurt, 60488
    Germany

    Active - Recruiting

  • Research Site

    Immenhausen, 34376
    Germany

    Active - Recruiting

  • Research Site

    Kiel, 24105
    Germany

    Site Not Available

  • Research Site

    Köln, 51109
    Germany

    Site Not Available

  • Research Site

    Mainz, 55131
    Germany

    Site Not Available

  • Research Site

    München, 81925
    Germany

    Site Not Available

  • Research Site

    Hong Kong,
    Hong Kong

    Site Not Available

  • Research Site

    Jordan, HKG
    Hong Kong

    Site Not Available

  • Research Site

    Lai Chi Kok,
    Hong Kong

    Site Not Available

  • Research Site

    Bangalore, 560027
    India

    Site Not Available

  • Research Site

    Delhi, 110085
    India

    Site Not Available

  • Research Site

    Hyderabad, 500032
    India

    Site Not Available

  • Research Site

    Kolkata, 700054
    India

    Site Not Available

  • Research Site

    Mysuru, 570017
    India

    Site Not Available

  • Research Site

    Nashik, 422011
    India

    Site Not Available

  • Research Site

    New Delhi, 100049
    India

    Site Not Available

  • Research Site

    Vadodara, 391760
    India

    Site Not Available

  • Research Site

    Varanasi, 221005
    India

    Suspended

  • Research Site

    Milano, 20141
    Italy

    Active - Recruiting

  • Research Site

    Monza, 20900
    Italy

    Active - Recruiting

  • Research Site

    Orbassano, 10043
    Italy

    Site Not Available

  • Research Site

    Padova, 35128
    Italy

    Active - Recruiting

  • Research Site

    Parma, 43100
    Italy

    Site Not Available

  • Research Site

    Chuo-ku, 104-0045
    Japan

    Active - Recruiting

  • Research Site

    Fukuoka-shi, 812-8582
    Japan

    Active - Recruiting

  • Research Site

    Kashiwa, 277-8577
    Japan

    Site Not Available

  • Research Site

    Koto-ku, 135-8550
    Japan

    Active - Recruiting

  • Research Site

    Niigata-shi, 951-8566
    Japan

    Site Not Available

  • Research Site

    Osaka-shi, 541-8567
    Japan

    Site Not Available

  • Research Site

    Osakasayama-shi, 589-8511
    Japan

    Site Not Available

  • Research Site

    Sendai-shi, 981-0914
    Japan

    Active - Recruiting

  • Research Site

    Wakayama-shi, 641-8510
    Japan

    Site Not Available

  • Research Site

    Yokohama-shi, 241-8515
    Japan

    Active - Recruiting

  • Research Site

    Erie, 16544
    Korea, Republic of

    Site Not Available

  • Research Site

    Goyang-si, 410-769
    Korea, Republic of

    Site Not Available

  • Research Site

    Namdong-gu, 21565
    Korea, Republic of

    Active - Recruiting

  • Research Site

    Seoul, 13620
    Korea, Republic of

    Active - Recruiting

  • Research Site

    Bystra, 43-360
    Poland

    Active - Recruiting

  • Research Site

    Olsztyn, 10-357
    Poland

    Active - Recruiting

  • Research Site

    Poznań, 60-569
    Poland

    Active - Recruiting

  • Research Site

    Warszawa, 02-781
    Poland

    Site Not Available

  • Research Site

    Rio Piedras, 00935
    Puerto Rico

    Site Not Available

  • Research Site

    Barcelona, 8036
    Spain

    Site Not Available

  • Research Site

    Granada, 18007
    Spain

    Site Not Available

  • Research Site

    La Coruña, 15006
    Spain

    Site Not Available

  • Research Site

    Madrid, 28040
    Spain

    Site Not Available

  • Research Site

    Majadahonda, 28222
    Spain

    Site Not Available

  • Research Site

    Valencia, 46009
    Spain

    Site Not Available

  • Research Site

    Taichung, 40705
    Taiwan

    Active - Recruiting

  • Research Site

    Tainan, 704
    Taiwan

    Active - Recruiting

  • Research Site

    Taipei, 10002
    Taiwan

    Active - Recruiting

  • Research Site

    Taipei City, 106
    Taiwan

    Active - Recruiting

  • Research Site

    Taoyuan, 333
    Taiwan

    Active - Recruiting

  • Research Site

    Bangkok, 10700
    Thailand

    Active - Recruiting

  • Research Site

    Dusit, 10300
    Thailand

    Active - Recruiting

  • Research Site

    Hat Yai, 90110
    Thailand

    Active - Recruiting

  • Research Site

    Mueang Udon Thani, 41000
    Thailand

    Active - Recruiting

  • Research Site

    Adana, 01140
    Turkey

    Site Not Available

  • Research Site

    Adapazarı, 54100
    Turkey

    Site Not Available

  • Research Site

    Ankara, 06530
    Turkey

    Site Not Available

  • Research Site

    Goztepe Istanbul,
    Turkey

    Site Not Available

  • Research Site

    Izmir, 35100
    Turkey

    Site Not Available

  • Research Site

    Küçükçekmece, 34295
    Turkey

    Site Not Available

  • Research Site

    Los Alamitos, California 90720
    United States

    Site Not Available

  • Research Site

    Los Angeles, California 90017
    United States

    Site Not Available

  • Research Site

    Orange, California 92868
    United States

    Site Not Available

  • Research Site

    San Diego, California 92123
    United States

    Site Not Available

  • Research Site

    New Haven, Connecticut 06510
    United States

    Site Not Available

  • Research Site

    Washington, District of Columbia 20037
    United States

    Site Not Available

  • Research Site

    Jacksonville, Florida 32256
    United States

    Site Not Available

  • Research Site

    Ocala, Florida 34474
    United States

    Site Not Available

  • Research Site

    Honolulu, Hawaii 96819
    United States

    Site Not Available

  • Research Site

    North Chicago, Illinois 60064
    United States

    Site Not Available

  • Research Site

    Fort Wayne, Indiana 46845
    United States

    Site Not Available

  • Research Site

    Bethesda, Maryland 20817
    United States

    Site Not Available

  • Research Site

    Detroit, Michigan 48201
    United States

    Site Not Available

  • Research Site

    Saint Paul, Minnesota 55102
    United States

    Site Not Available

  • Research Site

    Saint Louis, Missouri 63110
    United States

    Site Not Available

  • Research Site

    Houston, Texas 77090
    United States

    Site Not Available

  • Research Site

    Woodway, Texas 76712
    United States

    Site Not Available

  • Research Site

    Fairfax, Virginia 22031
    United States

    Site Not Available

  • Research Site

    Fort Belvoir, Virginia 22060
    United States

    Site Not Available

  • Research Site

    Seattle, Washington 98104
    United States

    Site Not Available

  • Research Site

    Ha noi, 100000
    Vietnam

    Active - Recruiting

  • Research Site

    Hanoi, 100000
    Vietnam

    Active - Recruiting

  • Research Site

    Ho Chi Minh, 700000
    Vietnam

    Active - Recruiting

  • Research Site

    Ho Chi Minh City,
    Vietnam

    Site Not Available

  • Research Site

    Vinh, 460000
    Vietnam

    Active - Recruiting

Not the study for you?

Let us help you find the best match. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.