PATRITUMAB DERUXTECAN for Non-small cell lung cancer (EGFR-mutated)

Inclusion criteria

• {"criterion_text":"- 1. Sign and date the tissue ICF and the main ICF, prior to the start of any study-specific qualification procedures.\n- 10. If the subject is a female of childbearing potential, she must have a negative serum pregnancy test at Screening and must be willing to use highly effective birth control, upon enrollment, during the Treatment Period, and for 7 months following the last dose of study drug. A female is considered of childbearing potential following menarche and until becoming postmenopausal (no menstrual period for a minimum of 12 months) unless permanently sterile (undergone a hysterectomy, bilateral salpingectomy or bilateral oophorectomy) with surgery at least 1 month before the first dose or confirmed by follicle stimulating hormone (FSH) test.\n- 11. 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 study drug administration.\n- 12. If male, the subject must be surgically sterile or willing to use highly effective birth control upon enrollment, during the treatment period, and for at least 4 months following the last dose of study drug.\n- 13. Male subjects must not freeze or donate sperm starting at Screening and throughout the study period, and at least 4 months after the final study drug administration.\n- 14. Is willing and able to comply with scheduled visits, drug administration plan, laboratory tests, other study procedures, and study restrictions.\n- 2. Male or female subjects aged ≥18 years (follow local regulatory requirements if the legal age of consent for study participation is >18 years old).\n- 3. Histologically or cytologically documented locally advanced or metastatic NSCLC not amenable to curative surgery or radiation.\n- 4. Documentation of radiological disease progression while on/after receiving most recent treatment regimen for locally advanced or metastatic disease. Subjects must have received both of the following: a. prior treatment with osimertinib. Subjects receiving an EGFR TKI at the time of signing informed consent should continue to take the EGFR TKI until 5 days prior to Cycle 1 Day 1. b. Systemic therapy with at least 1 platinum-based chemotherapy regimen.\n- 5. Documentation of an EGFR-activating mutation detected from tumor tissue or blood sample: exon 19 deletion or L858R.\n- 6. At least 1 measurable lesion confirmed by BICR as per RECIST v1.1\n- 7. Consented and willing to provide required tumor tissue of sufficient quantity (as defined in the Laboratory Manual) and of adequate tumor tissue content (as confirmed by H&E staining at the central laboratory). Required tumor tissue can be provided as either: a. Pretreatment tumor biopsy from at least 1 lesion not previously irradiated and amenable to core biopsy OR b. Archival tumor tissue collected from a biopsy performed within 3 months prior to signing of the tissue consent and since progression while on or after treatment with the most recent cancer therapy regimen.\n- 8. Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1 at Screening.\n- 9. Has adequate bone marrow reserve and organ function, based on local laboratory data within 14 days prior to Cycle 1 Day 1 as defined in the protocol."}

Exclusion criteria

• {"criterion_text":"- 1. Any previous or current histologic or cytologic evidence of small cell OR combined small cell/non-small cell disease in the archival tumor tissue or pretreatment tumor biopsy.\n- 10. Has unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0, Grade ≤1 or baseline. Subjects with chronic Grade 2 toxicities may be eligible at the discretion of the Investigator after consultation with the Sponsor Medical Monitor or designee.\n- 11. Has history of other active malignancy within 3 years prior to enrollment, except: a. Adequately treated non-melanoma skin cancer; b. Superficial bladder tumors (Ta, Tis, T1); c. Adequately treated intraepithelial carcinoma of the cervix uteri; d. Low risk non-metastatic prostate cancer (with Gleason score <7, and following local treatment or ongoing active surveillance); e. Any other curatively treated in situ disease.\n- 12. Uncontrolled or significant cardiovascular disease prior to Cycle 1 Day 1 as defined in the protocol points a/b/c/d/e/f/g (page 64).\n- 13. Active hepatitis B and/or hepatitis C infection, such as those with serologic evidence of viral infection within 28 days of Cycle 1 Day 1 as defined in the protocol points a/b (page 64).\n- 14. Subject with any human immunodeficiency virus (HIV) infection.\n- 15. Any evidence of severe or uncontrolled diseases including active bleeding diatheses, active infection, psychiatric illness/social situations, geographical factors, substance abuse, or other factors which in the Investigator's opinion makes it undesirable for the subject to participate in the study or which would jeopardize compliance with the protocol. Screening for chronic conditions is not required.\n- 16. History of hypersensitivity to either the drug substance or any excipients in patritumab deruxtecan.\n- 17. Female who is pregnant or breast-feeding or intends to become pregnant during the study.\n- 18. Prior or ongoing clinically relevant illness, medical condition, surgical history, physical finding, or laboratory abnormality that, in the Investigator's opinion, could affect the safety of the subject; alter the absorption, distribution, metabolism or excretion of the study drug; or confound the assessment of study results.\n- 19. Has clinically significant corneal disease.\n- 2. Any history of interstitial lung disease (including pulmonary fibrosis or radiation pneumonitis), has current interstitial lung disease (ILD), or is suspected to have such disease by imaging during screening.\n- 3. Clinically severe respiratory compromise (based on Investigator's assessment) resulting from intercurrent pulmonary illnesses including, but not limited to: a. Any underlying pulmonary disorder (eg, pulmonary emboli within 3 months prior to the study enrollment, severe asthma, severe chronic obstructive pulmonary disease [COPD], restrictive lung disease, pleural effusion); b. Any autoimmune, connective tissue or inflammatory disorders with pulmonary involvement (e.g., rheumatoid arthritis, Sjogren's syndrome, sarcoidosis); OR prior complete pneumonectomy.\n- 4. Is receiving chronic systemic corticosteroids dosed at >10 mg prednisone or equivalent anti-inflammatory or any form of immunosuppressive therapy prior to enrollment. Subjects who require use of bronchodilators, inhaled or topical steroids, or local steroid injections may be included in the study.\n- 5. Evidence of any leptomeningeal disease\n- 6. Evidence of clinically active spinal cord compression or brain metastases, defined as untreated and symptomatic, 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. Subjects must have a stable neurologic status for at least 2 weeks prior to Cycle 1 Day 1.\n- 7. Inadequate washout period prior to Cycle 1 Day 1 as defined in the protocol points a/b/c/d/e/f (page 53).\n- 8. Prior treatment with an anti-HER3 antibody or single-agent topoisomerase I inhibitor.\n- 9. Prior treatment with an ADC that consists of any topoisomerase I inhibitor"}

Primary endpoints

• {"endpoint_text":"- Objective Response Rate (ORR) as assessed by Blinded Independent Central Review (BICR) per RECIST v1.1","definition_or_measurement_approach":"Assessed by Blinded Independent Central Review (BICR) using RECIST v1.1"}

Secondary endpoints

• {"endpoint_text":"- -Duration of Response (DoR)","definition_or_measurement_approach":""}
• {"endpoint_text":"- - Progression-free Survival (PFS)","definition_or_measurement_approach":""}
• {"endpoint_text":"- - Objective Response Rate (ORR)","definition_or_measurement_approach":""}
• {"endpoint_text":"- - Disease Control Rate (DCR)","definition_or_measurement_approach":""}
• {"endpoint_text":"- - Time to Response (TTR)","definition_or_measurement_approach":""}
• {"endpoint_text":"- - Best percentage change in the sum of diameters (SoD) of measurable tumors","definition_or_measurement_approach":""}
• {"endpoint_text":"- - Overall Survival (OS)","definition_or_measurement_approach":""}
• {"endpoint_text":"- - Safety parameters (AEs, ECOG PS, vital signs, clinical laboratory parameters, ECG etc.)","definition_or_measurement_approach":"Safety assessed using adverse events (AEs), ECOG performance status, vital signs, clinical laboratory parameters, ECGs"}
• {"endpoint_text":"- - Correlation between HER3 protein expression and efficacy","definition_or_measurement_approach":"HER3 protein expression evaluated in tumor tissue and correlated with efficacy measures"}
• {"endpoint_text":"- - Anti-drug antibody (ADA) status at baseline and post-baseline.","definition_or_measurement_approach":"ADA status measured at baseline and at post-baseline timepoints"}

Belgium

Earliest CTIS Part Ii Submission Date

05-09-2024

Latest Decision Or Authorization Date

12-09-2024

Processing Time Days

7

Number Of Sites

1

Number Of Participants

1

Germany

Earliest CTIS Part Ii Submission Date

05-09-2024

Latest Decision Or Authorization Date

13-09-2024

Processing Time Days

8

Number Of Sites

2

Number Of Participants

4

France

Earliest CTIS Part Ii Submission Date

05-09-2024

Latest Decision Or Authorization Date

17-09-2024

Processing Time Days

12

Number Of Sites

6

Number Of Participants

25

Spain

Earliest CTIS Part Ii Submission Date

05-09-2024

Latest Decision Or Authorization Date

15-10-2024

Processing Time Days

40

Number Of Sites

1

Number Of Participants

23

Italy

Earliest CTIS Part Ii Submission Date

05-09-2024

Latest Decision Or Authorization Date

23-09-2024

Processing Time Days

18

Number Of Sites

1

Number Of Participants

17

Netherlands

Earliest CTIS Part Ii Submission Date

05-09-2024

Latest Decision Or Authorization Date

12-09-2024

Processing Time Days

7

Number Of Sites

1

Number Of Participants

6

Primary sponsor

Full Name

Daiichi Sankyo Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Pharmaceutical Product Development LLC

Responsibilities

PK/ ADA Bioanalysis

Name

Syneos Health Inc.

Responsibilities

Site management (and other operational duties as coded in CTIS)

Third parties

• {"country":"United States","full_name":"Guardant Health Inc.","duties_or_roles":"cfDNA / ctDNA OMNI","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Pharmaceutical Product Development LLC","duties_or_roles":"PK/ ADA Bioanalysis","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Bioclinica Inc.","duties_or_roles":"Medical image analysis/review- X-ray, MRI, ultrasound, etc.","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Ventana Medical Systems Inc.","duties_or_roles":"Protein testing; HER3 IHC reagent development, validation, qualification of Q2 lab, reagent supply, clinical monitoring of HER3 IHC testing","organisation_type":"Pharmaceutical company"}
• {"country":"Japan","full_name":"Daiichi Sankyo Rd Novare Co. Ltd.","duties_or_roles":"mRNA Gene Expression, yH2AX IHC, PD-L1 or other BM with multiplex IHC, cfRNA","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Q Squared Solutions Holdings LLC","duties_or_roles":"IHC HER3, Real Time GT-PCR COVID-19 Testing","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Syneos Health Inc.","duties_or_roles":"Site management (other duties coded in CTIS: 1,12,2,5,8)","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Azenta US Inc.","duties_or_roles":"Storage of samples for future research.","organisation_type":"Pharmaceutical company"}