Phase 3 Study of Patritumab Deruxtecan Versus Platinum-based Chemotherapy in Metastatic or Locally Advanced EGFRm NSCLC After Failure of EGFR TKI Therapy

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 Sep 2022 → ongoing

Decision date (initial)

2024-10-14

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Daiichi Sankyo Inc

External identifiers

EU CT number

2023-507964-38-00

EudraCT number

2021-005879-40

ClinicalTrials.gov

NCT05338970

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacogenetic, Others, Pharmacokinetic, Efficacy, Pharmacogenomic, Therapy, Pharmacoeconomic

To compare the efficacy of patritumab deruxtecan versus platinum-based chemotherapy, as measured by progression-free survival (PFS), in subjects with metastatic or locally advanced nonsquamous non-small cell lung cancer (NSCLC) with an EGFR-activating mutation (exon 19 deletion or L858R)

Secondary objectives 3

1. To compare the efficacy of patritumab deruxtecan versus platinum-based chemotherapy, as measured by OS, in subjects with metastatic or locally advanced nonsquamous NSCLC with an EGFR-activating mutation (exon 19 deletion or L858R)
2. To further evaluate the efficacy of patritumab deruxtecan compared with platinum-based chemotherapy in subjects with metastatic or locally advanced nonsquamous NSCLC with an EGFR-activating mutation (exon 19 deletion or L858R)
3. To evaluate symptoms, functioning and global health for patritumab deruxtecan compared with platinum-based chemotherapy in subjects with metastatic or locally advanced nonsquamous NSCLC with an EGFRactivating mutation (exon 19 deletion or L858R) based on PROs. Please refer to the protocol for full list of secondary objectives.

Conditions and MedDRA coding

Metastatic or Locally Advanced Epidermal Growth Factor Receptor-mutated (EGFRm) Non-small Cell Lung Cancer (NSCLC)

Regulatory references

Scientific advice from competent authorities

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 16

1. Sign and date the main ICF, prior to the start of any study-specific qualification procedures. Consent for the optional samples for EOT tumor biopsy and/or pharmacogenetic analysis will be covered in the main ICF.
2. Is a male or female subject aged ≥18 years (follow local regulatory requirements if the legal age of consent for study participation is >18 years old).
3. Has histologically or cytologically documented metastatic or locally advanced nonsquamous NSCLC not amenable to curative surgery or radiation.
4. Has documentation of an EGFR-activating mutation detected from tumor tissue or from a blood sample: exon 19 deletion or L858R at diagnosis or thereafter.
5. Received 1 or 2 prior line(s) of an approved EGFR TKI treatment in the metastatic or locally advanced setting, which must include a thirdgeneration EGFR TKI (ie, approved therapies designed with higher preferential activity for mutant vs. EGFRwt and that address acquired resistance to first- and second-generation EGFR TKI [eg, osimertinib, lazertinib, aumolertinib, alflutinib, and others in consultation with Medical Monitor]). If a subject has received 2 prior lines of EGFR TKI therapy, administration of the third-generation EGFR TKI must have been in the most recent line. Subject must have documentation of T790M mutation if subjects had treatment with a first- or second-generation EGFR TKI prior to treatment with a third-generation EGFR TKI. Enrollment of subjects receiving third-generation EGFR TKIs other than osimertinib will be a maximum of approximately 20% of the enrolled population in each treatment arm.
6. May have received either neoadjuvant and/or adjuvant treatment if progression to metastatic or locally advanced disease occurred at least 12 months after the last dose of such therapy and subsequently experienced disease progression on or after third-generation EGFR TKI treatment administered in the metastatic or locally advanced setting. a. To provide an example, a patient who received osimertinib as adjuvant therapy after tumor resection, then progressed to having metastatic disease over a year following completion of adjuvant therapy must have also received a third-generation EGFR TKI as treatment for metastatic disease to be considered eligible for this study.
7. Has not received any other prior systemic therapies in the metastatic or locally advanced setting (including chemotherapy, immunotherapy etc) (even if administered in combination with EGFR TKI).
8. Has documentation of radiographic disease progression while receiving or after a third-generation EGFR TKI for metastatic or locally advanced disease.
9. Has at least 1 measurable lesion as per RECIST v1.1 by Investigator assessment.
10. Is willing to provide sufficient quantity and quality of tumor tissue content.
11. Has an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1 at Screening.
12. Has adequate bone marrow reserve and organ function based on local laboratory data within 14 days prior to randomization as described in the protocol.
13. If the subject is a female of childbearing potential, must have a negative serum pregnancy test at Screening and must be willing to use highly effective birth control upon randomization, during the Treatment Period, and for 7 months following the last dose of patritumab deruxtecan. A female is considered to be of childbearing potential following menarche and until becoming postmenopausal (no menstrual period for a minimum of 12 months) or if permanently sterile (undergone a hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) with surgery at least 1 month before randomization or confirmed by follicle stimulating hormone (FSH) test. For comparator drugs, the investigators should follow local practice guidelines and/or label approved in their country.
14. Female subjects must not donate, or retrieve for their own use, ova from the time of Screening and throughout the study Treatment Period and for at least 7 months after the final patritumab deruxtecan administration. For comparator drugs, the investigators should follow local practice guidelines and/or label approved in their country.
15. If male, must be surgically sterile or willing to use highly effective birth control upon randomization, during the Treatment Period, and for at least 4 months following the last dose of patritumab deruxtecan. For comparator drugs, the investigators should follow local practice guidelines and/or label approved in their country.
16. Male subjects must not freeze or donate sperm starting at Screening and throughout the study period and at least 4 months after the final patritumab deruxtecan administration. For comparator drugs, the investigators should follow local practice guidelines and/or label approved in their country. For the full list of criteria, please see section 5.1 in protocol.

Exclusion criteria 16

1. Has any previous histologic or cytologic evidence of small cell OR combined small cell/non-small cell disease in the archival tumor tissue or pretreatment tumor biopsy, or squamous NSCLC histology.
2. Has any history of ILD (including pulmonary fibrosis or radiation pneumonitis), has current ILD, or is suspected to have such disease by imaging during Screening.
3. Has clinically severe respiratory compromise (based on the Investigator's assessment) resulting from intercurrent pulmonary illnesses as described in the protocol.
4. Is receiving chronic systemic corticosteroids dosed at >10 mg prednisone or equivalent anti-inflammatory activity or any form of immunosuppressive therapy prior to randomization. Subjects who require use of bronchodilators, inhaled or topical steroids, or local steroid injections may be included in the study.
5. Has any history of or evidence of current leptomeningeal disease.
6. Has evidence of clinically active spinal cord compression or brain metastases, defined as being symptomatic and untreated, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms. Subjects with clinically inactive or treated brain metastases who are asymptomatic (i.e., without neurologic signs or symptoms and not requiring treatment with corticosteroids or anticonvulsants) may be included in the study but must have a stable neurologic status for at least 2 weeks prior to randomization. Subjects with asymptomatic brain metastases and treated with anticonvulsants as prophylaxis are able to enroll
7. Has had inadequate washout period prior to randomization defined as follows: a. Whole-brain radiation therapy < 28 days or stereotactic brain radiation therapy <7 days. b. Major surgery (excluding placement of vascular access) <28 days. c. Radiotherapy treatment to >30% of the bone marrow or with a wide field of radiation <28 days or palliative radiation therapy < 7 days. d. Chloroquine or hydroxychloroquine ≤14 days. e. Live virus vaccination ≤28 days
8. Has had prior treatment with the following: a. Any agent including an ADC containing a chemotherapeutic agent targeting topoisomerase I. b. HER3 antibody. c. Any systemic therapies (other than EGFR TKIs) in the metastatic or locally advanced setting, including chemotherapy or any other systemic therapy in combination with an EGFR TKI.
9. Has unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved by the National Cancer Institute - Common Terminology Criteria for Adverse Events Version 5.0 (NCI-CTCAE v5.0), Grade ≤1 or baseline. Subjects with chronic Grade 2 toxicities [defined as no worsening to Grade >2 for at least 3 months prior to randomization and managed with SoC treatment]) that the Investigator deems related to previous anticancer therapy may be randomized.
10. Has history of other active malignancy within 3 years prior to randomization, except the following: a. Adequately resected nonmelanoma skin cancer. b. Adequately treated intraepithelial carcinoma of the cervix. c. Any other curatively treated in situ disease.
11. Has uncontrolled or significant cardiovascular disease prior to randomization as described in the protocol.
12. Has active hepatitis B and/or hepatitis C infection, such as those with serologic evidence of active viral infection within 28 days of randomization.
13. Has a known HIV infection that is not well controlled. All the following criteria are required to define an HIV infection that is well controlled: undetectable viral ribonucleic acid (RNA) load, CD4+ counts/levels of >350 cells/μL, no history of AIDS-defining opportunistic infection within the past 12 months, and stable for at least 3 weeks on same anti-HIV retroviral medications. If an HIV infection meets the above criteria, the subject's viral RNA load and CD4+ cell count should be monitored per local SoC (e.g., every 3 months).
14. Has any evidence of severe or uncontrolled diseases (eg, active bleeding diatheses, active infection) psychiatric illness/social situations, geographical factors, substance abuse, or other factors that, in the Investigator's opinion, make it undesirable for the subject to participate in the study or that would jeopardize compliance with the protocol. Screening for chronic conditions is not required for eligibility.
15. Has known hypersensitivity to either the drug substance or inactive ingredients in any of the drug products.
16. Is a female who is pregnant or breastfeeding or intends to become pregnant during the study. For the full list of criteria, please see section 5.2 in protocol.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Progression free survival (PFS) as assessed by blinded independent central review (BICR) based on RECIST v1.1

Secondary endpoints 10

1. Overall survival (OS)
2. Progression-free survival (PFS) as assessed by the Investigator per RECIST v1.1
3. Progression-free survival on the next line of therapy (PFS2) as assessed by local standard clinical practice
4. Objective response rate (ORR) as assessed by BICR and as assessed by the Investigator per RECIST v1.1
5. Duration of response (DoR) as assessed by BICR and as assessed by the Investigator per RECIST v1.1
6. Clinical benefit rate (CBR) as assessed by BICR and as assessed by the Investigator per RECIST v1.1
7. Disease control rate (DCR) as assessed by BICR and as assessed by the Investigator per RECIST v1.1
8. Time to response (TTR) as assessed by BICR and as assessed by the Investigator per RECIST v1.1
9. Patient-reported outcome (PRO) of disease-related symptoms, functioning scales, and general health status and overall quality of life
10. Intracranial progression-free survival (PFS) as assessed by BICR per CNS—RECIST.

Investigational products

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

Test 1

Comparator 4

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

Clinical Trial Office

Public contact point

Organisation

Daiichi Sankyo Inc.

Contact name

Clinical Trial Office

Third parties 18

Locations

10 EU/EEA countries · 48 investigational sites

By country

Investigational sites

Country notifications

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

Results and documents

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

Documents 190 files

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

Application history

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