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 Non-Small Cell Lung Cancer (TROPION-Lung07)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Daiichi Sankyo Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

1 Nov 2023 → ongoing

Decision date (initial)

2023-04-11

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

DAIICHI SANKYO, INC

External identifiers

EU CT number

2022-500802-16-00

ClinicalTrials.gov

NCT05555732

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Safety, Efficacy

To compare the efficacy of Dato-DXd in combination with pembrolizumab with or without platinum-based chemotherapy versus pembrolizumab plus pemetrexed and platinum-based chemotherapy, as measured by Progression-Free Survival (PFS) by blinded independent central review (BICR).

To compare the efficacy of Dato-DXd in combination with pembrolizumab with or without platinum-based chemotherapy versus pembrolizumab plus pemetrexed and platinum-based chemotherapy, as measured by Overall Survival (OS).

To compare the efficacy of Dato-DXd in combination with pembrolizumab with or without platinum-based chemotherapy versus pembrolizumab plus pemetrexed and platinum-based chemotherapy, as measured by Progression-Free Survival (PFS) by blinded independent central review (BICR).

To compare the efficacy of Dato-DXd in combination with pembrolizumab with or without platinum-based chemotherapy versus pembrolizumab plus pemetrexed and platinum-based chemotherapy, as measured by OS.

Secondary objectives 1

1. To compare the efficacy of Dato-DXd in combination with pembrolizumab with or without platinum-based chemotherapy versus pembrolizumab plus pemetrexed and platinumbased chemotherapy, as measured by objective response rate (ORR). To further evaluate the efficacy of Dato-DXd in combination with pembrolizumab with or without platinum-based chemotherapy versus pembrolizumab plus platinum- pemetrexed chemotherapy in. To evaluate the patient-reported outcomes (PROs) of Dato-DXd in combination with pembrolizumab with or without platinum-based chemotherapy versus pembrolizumab plus platinum- pemetrexed chemotherapy. To further evaluate the safety of Dato-DXd in combination with pembrolizumab with or without platinum-based chemotherapy versus pembrolizumab plus platinum- pemetrexed chemotherapy. To assess the immunogenicity of Dato-DXd in combination with pembrolizumab with or without platinum-based chemotherapy. To compare the efficacy of Dato-DXd in combination with pembrolizumab with or without platinum-based chemotherapy versus pembrolizumab plus pemetrexed and platinum-based chemotherapy, as measured by objective response rate (ORR).

Conditions and MedDRA coding

Advanced or Metastatic PD-L1 TPS <50% Non-squamous Non-small Cell Lung Cancer Without Actionable Genomic Alterations

Study design 3 periods

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration, Pharmaceuticals And Medical Devices Agency, European Medicines Agency

Plan to share IPD

Yes

IPD plan description

De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. 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. 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. 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. 4. Has provided a formalin-fixed tumor tissue sample (minimum of 10 [preferably 15] × 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. 5. Has not been treated with systemic anticancer therapy for advanced or metastatic nonsquamous 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. 6. Has measurable disease based on local imaging assessment using RECIST v1.1; radiographic tumor assessment must be performed within 28 days before randomization. For more details regaridng the inclusion criteria please refer to protocol section 5.1

Exclusion criteria 5

1. 1. Has received prior systemic treatment for advanced/metastatic NSCLC.
2. 2. Has received prior treatment with any of the following, including in the adjuvant/neoadjuvant setting: a. Any agent, including an ADC, containing a chemotherapeutic agent targeting topoisomerase I b. TROP2-targeted therapy c. Any anti-PD-1, anti-PD-L1, or anti-programmed death-ligand (PD-L2) agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX40, CD137) d. 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. 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-Guérin (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-CoV2) 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, 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. 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 4 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 should consider delay of study treatment to document stability of CNS metastases with repeat imaging at least 4 weeks later (in which case, repeat of all screening activity may be required).
5. 5. Has uncontrolled or significant cardiovascular disease not controlled by maximal medical therapy, including: a. 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). b. Myocardial infarction within 6 months prior to Cycle 1 Day 1. c. History of a serious cardiac arrhythmia requiring treatment d. Uncontrolled angina pectoris within 6 months prior to Cycle 1 Day 1. e. Left ventricular ejection fraction (LVEF) <50% by echocardiogram (ECHO) or multigated acquisition (MUGA) scan within 28 days before randomization. f. 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. g. 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). For more deatails about the exclusion criteria, please refer to protocol section 5.2

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Progression-Free Survival (PFS) is defined as the time from randomization to the first documented radiographic disease progression or death due to any cause, whichever occurs first. Overall Survival (OS) is defined as the time from randomization to death due to any cause.

Secondary endpoints 11

1. Objective response rate (ORR) is defined as the proportion of subjects who achieved a Best Overall Response (BOR) of confirmed complete response (CR) or confirmed partial response (PR).
2. PFS is defined as the time from randomization to the first documented radiographic disease progression or death due to any cause, whichever occurs first.
3. ORR is defined as the proportion of subjects who achieved a BOR of CR or confirmed partial PR.
4. Duration of response (DoR) in a responding subject 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 radiographic disease progression or death due to any cause, whichever occurs first.
5. Time to response (TTR) is defined as the time from randomization to the date of the first documentation of objective response (confirmed CR or confirmed PR) in responding subjects.
6. Disease Control Rate (DCR) is defined as the proportion of subjects who achieved a BOR of confirmed CR, confirmed PR, or stable disease (SD).
7. PFS2 is defined as the time from the date of randomization to the first documented disease progression on next-line therapy or death due to any cause, whichever occurs first.
8. The time to deterioration (TTD) is defined as the time from randomization to the first onset of a ≥10-point increase in cough, chest pain, or dyspnea, confirmed by a second adjacent ≥10-point increase from randomization in the same symptom, or confirmed by death within 21 days of a ≥10-point increase from randomization.
9. Treatment emergent adverse events (TEAEs), serious adverse events (SAEs), adverse events of special interest (AESIs), Eastern Cooperative Oncology Group performance status (ECOG PS), vital sign measurements, standard clinical laboratory parameters (hematology, clinical chemistry, and urinalysis), electrocardiogram parameters, echocardiogram (ECHO)/multigated acquisition (MUGA) scan findings, and ophthalmologic findings.
10. Adverse events (AEs) will be coded by the most recent version of the Medical Dictionary for Regulatory Activities (MedDRA) and both AEs and laboratory test results will be graded by the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCICTCAE) version 5.0.
11. ADA prevalence: the proportion of subjects who are ADA-positive at any point in time (at baseline or post-baseline). ADA incidence: the proportion of subjects having a treatmentemergent ADA. Titer and neutralizing antibodies will be determined when the ADA is positive.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Daiichi Sankyo Inc.

Sponsor organisation

Daiichi Sankyo Inc.

Address

211 Mount Airy Road

City

Basking Ridge

Postcode

07920-2311

Country

United States

Scientific contact point

Organisation

Daiichi Sankyo Inc.

Contact name

Director Regulatory Affairs Lead EU Clinical Trial Office

Public contact point

Organisation

Daiichi Sankyo Inc.

Contact name

Director Regulatory Affairs Lead EU Clinical Trial Office

Third parties 11

Locations

13 EU/EEA countries · 88 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Serious breaches 1 · Art. 52 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 415 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

36 submissions — initial application plus substantial / non-substantial modifications