Protocol for the clinical performance study for PD-L1 IHC 22C3 pharmDx on samples from non-squamous, non-small cell lung cancer without treatable genomic alterations. Supplement to the protocol of the Phase III clinical study DS1062-A-U303 TROPION-Lung07 (BASEC 2023-00195).

Argentina, Australia, Austria, Belgium, Brazil, Canada, Chile, China, Czechia, France, Germany, Greece, Hong Kong, Hungary, Italy, Japan, Mexico, Netherlands, Poland, Portugal, Romania, South Korea, Spain, Switzerland, Taiwan, Thailand, Turkey (T�rkiye), United Kingdom, United States (ICTRP)

ICTRP Trial ID
NCT05555732 (ICTRP)

Official title (approved by ethics committee)
Clinical Performance Study for PD-L1 IHC 22C3 pharmDx on Non- Squamous Non-Small Cell Lung Cancer Specimens, Supplement to Clinical Trial Protocol DS1062-A-U303 (BASEC)

Academic title
A Randomized Phase 3 Study of Datopotamab Deruxtecan (Dato-DXd) and Pembrolizumab With or Without Platinum Chemotherapy in Subjects With No Prior Therapy for Advanced or Metastatic PD-L1 TPS <50% Non-squamous Non-small Cell Lung Cancer Without Actionable Genomic Alterations (TROPION-Lung07) (ICTRP)

Public title
Datopotamab Deruxtecan (Dato-DXd) and Pembrolizumab With or Without Platinum Chemotherapy in 1L Non-Small Cell Lung Cancer (TROPION-Lung07) (ICTRP)

Disease under investigation
Metastatic Non Small Cell Lung Cancer (ICTRP)

Intervention under investigation
Drug: Datopotamab DeruxtecanDrug: PembrolizumabDrug: PemetrexedDrug: CarboplatinDrug: Cisplatin (ICTRP)

Type of trial
Interventional (ICTRP)

Trial design
Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label). (ICTRP)

Inclusion/Exclusion criteria
Key Inclusion Criteria:

1. Sign and date the Main ICF, prior to the start of any study- specific qualification
procedures. Is willing and able to comply with scheduled visits, drug administration
plan, laboratory tests, other study procedures, and study restrictions.

2. Adults =18 at the time the Main ICF is signed. (Follow local regulatory requirements
if the legal age of adult voluntary consent for study participation is >18 years
old).

3. Has tumor with PD-L1 TPS <50% as determined by PD-L1 IHC 22C3 pharmDx assay by
central testing (minimum of 6 slides). PD-L1 expression results available at the
same central laboratory from screening for the purpose of entry into another
Dato-DXd study may be used for tissue screening purposes in this study as long as
the subject has not been randomized/enrolled in the other study.

4. Has provided a formalin-fixed tumor tissue sample (minimum of 4 4-micron sections
or block equivalent) for the measurement of TROP2 protein expression and for the
assessment of other exploratory biomarkers. This tissue requirement is in addition
to the tissue required for PD-L1 testing for tissue screening purposes. If a
documented law or regulation prohibits (or does not approve) sample collection, then
such sample will not be collected, and the subject is still eligible for the study.

5. Has not been treated with systemic anticancer therapy for advanced or metastatic
non-squamous NSCLC. Subjects who received adjuvant or neoadjuvant therapy other than
those listed in the exclusion criteria are eligible if the adjuvant/ neoadjuvant
therapy was completed at least 6 months prior to the diagnosis of
advanced/metastatic disease and should not have progressed on or within the 6 months
of completion.

6. Has measurable disease based on local imaging assessment using RECIST v1.1
radiographic tumor assessment must be performed within 28 days before randomization.

Key Exclusion Criteria:

1. Has received prior systemic treatment for advanced/metastatic NSCLC.

2. Has received prior treatment with any of the following, including in the
adjuvant/neoadjuvant setting (for NSCLC):

1. Any agent, including an ADC, containing a chemotherapeutic agent targeting
topoisomerase I

2. TROP2-targeted therapy

3. Any anti-PD-1, anti-PD-L1, or anti-programmed death-ligand 2 (PD-L2) agent or
with an agent directed to another stimulatory or co-inhibitory T-cell receptor
(eg, CTLA-4, OX40, CD137)

4. Any other ICIs Subjects who received adjuvant or neoadjuvant therapy other than
those listed above are eligible if the adjuvant/neoadjuvant therapy was
completed at least 6 months prior to the diagnosis of advanced or metastatic
disease.

3. Has received a live vaccine within 30 days prior to the first dose of study
treatment.

Examples of live vaccines include, but are not limited to, the following: measles,
mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus
Calmette-Gurin (BCG), and typhoid vaccine. Seasonal influenza vaccines for
injection are generally killed virus vaccines and are allowed however, intranasal
influenza vaccines (eg, FluMist) are live attenuated vaccines and are not allowed.
For any subject receiving an approved severe acute respiratory syndrome
coronavirus-2 (SARS-CoV-2) vaccine, please follow the vaccine label and/or local
guidance. The vaccine manufacturer and the date of administration should be recorded
on the electronic case report form (Concomitant Medications page), as should any AEs
relating to the vaccine (including hypersensitivity or allergies). Note: Any
licensed SARS-CoV2 vaccine (including those authorized for emergency use) in a
particular country is allowed in the study as long as the vaccine is an mRNA
vaccine, replication-incompetent adenoviral vaccine, or inactivated vaccine. Such
vaccines will be treated just as any other concomitant therapy.

Investigational vaccines (ie, those not licensed or authorized for emergency use)
are not allowed.

4. Has spinal cord compression or clinically active untreated CNS metastases and/or
carcinomatous meningitis. Subjects with previously treated brain metastases may
participate provided they are radiologically stable (ie, without evidence of
progression) for at least 2 weeks by repeat imaging (Note: Repeat imaging should be
performed during study screening), clinically stable, and without requirement of
steroid treatment for at least 7 days before the first dose of study drug. Note: A
contrasted computed tomography (CT) scan or magnetic resonance imaging (MRI) scan of
the brain at baseline (MRI with contrast preferred) is required for all subjects.
For those subjects in whom CNS metastases are first discovered at the time of
screening, the treating investigator must delay of study treatment to document
stability of CNS metastases with repeat imaging at least 2 weeks later (in which
case, repeat of all screening activity may be required).

5. Has uncontrolled or significant cardiovascular disease not controlled by maximal
medical therapy, including:

1. Mean QT interval corrected for heart rate using Fridericia's formula (QTcF)
interval >470 msec regardless of sex (based on the 12-lead electrocardiogram
[ECG] performed at screening).

2. Myocardial infarction within 6 months prior to Cycle 1 Day 1.

3. History of a serious cardiac arrhythmia requiring treatment

4. Uncontrolled angina pectoris within 6 months prior to Cycle 1 Day 1.

5. Left ventricular ejection fraction (LVEF) <50% by echocardiogram (ECHO) or
multigated acquisition (MUGA) scan within 28 days before randomization.

6. New York Heart Association (NYHA) Class II-IV congestive heart failure (CHF) at
screening. Subjects with a history of Class II to IV CHF prior to screening,
must have returned to Class I CHF and have LVEF =50% (by either an ECHO or MUGA
scan within 28 days before randomization) in order to be eligible.

7. Uncontrolled hypertension (resting systolic blood pressure >180 mmHg or
diastolic blood pressure >110 mmHg within 28 days before randomization that is
not resolved despite maximal medical therapy).

6. Clinically severe pulmonary compromise as judged by the investigator resulting from
intercurrent pulmonary illnesses including, but not limited to, any underlying
pulmonary disorder (eg, pulmonary emboli diagnosed within 3 months of Cycle 1 Day 1,
severe asthma, severe chronic obstructive pulmonary disease, restrictive lung
disease, pleural effusion, etc) or any autoimmune, connective tissue or inflammatory
disorders with pulmonary involvement (eg, rheumatoid arthritis, Sjgren's syndrome,
sarcoidosis, etc), or prior complete pneumonectomy. (ICTRP)

not available

Primary and secondary end points
Progression-free Survival Based on Blinded Independent Central Review in All Randomized Participants;Progression-free Survival Based on Blinded Independent Central Review in All Randomized Participants who are TROP2 NMR positive;Overall Survival in All Randomized Participants;Overall Survival in All Randomized Participants who are TROP2 NMR positive (ICTRP)

Objective Response Rate by Blinded Independent Central Review in All Randomized Participants;Objective Response Rate by Blinded Independent Central Review in All Randomized Participants who are TROP2 NMR positive;Progression-free Survival by Investigator in Both All Randomized Participants and Randomized Participants who are TROP2 NMR positive;Objective Response Rate by Investigator in Both All Randomized Participants and Randomized Participants who are TROP2 NMR positive;Duration of Response by BICR and Investigator in Both All Randomized Participants and Randomized Participants who are TROP2 NMR positive;Time to Response by BICR and Investigator in Both All Randomized Participants and Randomized Participants who are TROP2 NMR positive;Disease Control Rate by BICR and Investigator in Both All Randomized Participants and Randomized Participants who are TROP2 NMR positive;Progression-free Survival 2 in Both All Randomized Participants and Randomized Participants who are TROP2 NMR positive;Time to Deterioration;Number of Participants With Treatment-emergent Adverse Events (TEAE);Proportion of Participants Who Are Anti-Drug Antibody (ADA)-Positive (Baseline and Post-Baseline) and Proportion of Participants Who Have Treatment-emergent ADA (ICTRP)

Registration date
not available

Incorporation of the first participant
not available

Secondary sponsors
AstraZeneca;Merck Sharp & Dohme LLC (ICTRP)

Additional contacts
Global Clinical Leader;Daiichi Sankyo Contact for Clinical Trial Information, CTRinfo_us@daiichisankyo.com, 908-992-6400, Daiichi Sankyo, (ICTRP)

Secondary trial IDs
2022-500802-16-00, MK-3475-E10, jRCT2061220066, TROPION-Lung07, KEYNOTE-E10, DS1062-A-U303 (ICTRP)

Results-Individual Participant Data (IPD)
not available

Further information on the trial
https://clinicaltrials.gov/study/NCT05555732 (ICTRP)