SIGVOTATUG VEDOTIN for Non-small cell lung cancer

Inclusion criteria

• {"criterion_text":"- Participants must meet the following criteria: a. 18 years of age or older (or the minimum age of consent in accordance with local regulations) at screening. b. Participants must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. c. Participants must have adequate baseline hematologic, hepatic, and renal function. d. Have pathologically confirmed Stage IIIB or IIIC NSCLC and not be a candidate for surgical resection or definitive chemoradiation, or Stage IV NSCLC per the American Joint Committee on Cancer (AJCC) Staging Manual (Version 8.0) and the Union for International Cancer Control (UICC) Staging System (Eighth edition). e. Participants with non-squamous histology must have documented negative test results for epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), and c-ros oncogene 1 (ROS1) actionable genomic alterations (AGAs) and no known AGAs in neurotrophic tyrosine receptor kinase (NTRK), proto-oncogene B-raf (BRAF), rearranged during transfection (RET),mesenchymal-epithelial transition factor (MET), or other AGAs with approved front-line therapies per local standard of care. f. Must not have small cell elements present. g. Large cell neuroendocrine carcinoma is excluded. h. Must be an appropriate candidate for treatment with pembrolizumab monotherapy per local guidelines.\n- Tumor has PD-L1 expression in ≥50% of tumor cells as determined by local testing with retrospective central confirmation using a PD-L1 IHC assay. a. Tumor sample (formalin fixed paraffin embedded [FFPE]) acquired at screening must be collected according to Laboratory Manual standards and must be made available to the Sponsor for central laboratory confirmation. b. Archival tumor specimen that has been collected within 6 months prior to first dose of study intervention may be used. c. If no archival tissue is available, the participant must be willing and able to undergo a biopsy procedure to obtain a tumor tissue specimen.\n- Measurable disease based on RECIST v1.1 per investigator. Participants with prior definitive radiotherapy must have measurable disease per RECIST v1.1 that is outside the radiation field or have unequivocal progression of previously irradiated lesions (see exclusion criterion 15c in full protocol)."}

Exclusion criteria

• {"criterion_text":"- Prior and concomitant therapy: a. Any prior treatment with MMAE derived drugs or integrin beta-6 targeting agents. b. Prior systemic therapy, including anti-PD-L1 or anti-programmed cell death receptor 1 (PD-1, collectively PD-[L]1) therapy, for locally advanced, unresectable, or metastatic NSCLC.  (Neo)adjuvant anti-PD-(L)1 is allowed if recurrence or progression occurred ≥9 months after the last dose.  Other (neo)adjuvant or definitive therapy is allowed if recurrence or progression occurred ≥6 months after the last dose. c. Prior radiotherapy to the lung within 6 months of first dose of study intervention, referencing the last date radiotherapy was received. d. Chemotherapy, biologics, and/or other antitumor treatment with immunotherapy not specifically prohibited that is completed less than 4 weeks prior to first dose of study intervention, or 2 weeks for palliative radiotherapy.  Participants must have recovered from all radiation related toxicities that would otherwise prevent trial participation.  Ongoing hormonal/antihormonal treatment (eg, for breast cancer, prostate cancer) is allowed, provided that the participant is eligible per synopsis exclusion criterion 3. e. Current therapy with an investigational agent. f. Any prior therapy with an immune-oncology agent directed to a stimulatory or co-inhibitory T-cell receptor (eg, CTLA4, LAG-3, TIGIT, OX 40, 41-BB, PD-L2, CD137). g. Treatment with any prohibited concomitant therapy within 21 days of the first dose of study intervention."}
• {"criterion_text":"- Participants with any of the following respiratory conditions: a. Evidence of noninfectious or drug-induced ILD or pneumonitis that:  Was previously diagnosed and required systemic steroids, or  Is currently diagnosed and managed, or  Is suspected on radiologic imaging at screening b. Known diffusing capacity of the lung for carbon monoxide (DLCO) (adjusted for hemoglobin) <50% predicted. c. Any Grade ≥3 pulmonary disease unrelated to underlying malignancy including, but not limited to:  Severe asthma requiring systemic corticosteroids within 30 days prior to first dose of study intervention or not well controlled with low-dose inhaled corticosteroids/long-acting beta-2 agonists.  Severe chronic obstructive pulmonary disease requiring supplemental oxygen or systemic corticosteroids.  Clinically severe and/or Grade 4 pulmonary emboli within 3 months of the first dose of study intervention. Pulmonary emboli in main or lobar pulmonary arteries are also excluded.  Any autoimmune or inflammatory disorders with significant pulmonary parenchymal involvement at time of screening (ie, rheumatoid arthritis, Sjogren’s syndrome, sarcoidosis, etc)."}
• {"criterion_text":"- Known active central nervous system (CNS) lesions, including leptomeningeal metastasis, are excluded. Participants with definitively treated brain metastases (surgery and/or radiotherapy) are eligible if they meet the following criteria: a. CNS metastases have been clinically stable with no evidence of clinical or radiographic disease progression for ≥14 days after completion of definitive radiotherapy and/or surgery and prior to study intervention. b. The participant has not required steroids for brain metastasis symptom management for 7 days prior to first dose of study intervention. c. Clinically inactive brain metastases of longest diameter <0.5 cm are permitted."}

Primary endpoints

• {"endpoint_text":"- OS","definition_or_measurement_approach":"Overall Survival (OS)"}
• {"endpoint_text":"- PFS using Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1) as assessed by BICR","definition_or_measurement_approach":"Progression-free survival assessed per RECIST v1.1 by Blinded Independent Central Review (BICR)"}

Secondary endpoints

• {"endpoint_text":"- Confirmed ORR using RECIST v1.1 as assessed by BICR","definition_or_measurement_approach":"Objective response rate per RECIST v1.1 assessed by Blinded Independent Central Review (BICR)"}
• {"endpoint_text":"- PFS using RECIST v1.1 as assessed by investigator","definition_or_measurement_approach":"Progression-free survival per RECIST v1.1 assessed by investigator"}
• {"endpoint_text":"- Confirmed ORR using RECIST v1.1 as assessed by investigator","definition_or_measurement_approach":"Objective response rate per RECIST v1.1 assessed by investigator"}
• {"endpoint_text":"- Duration of response (DOR) using RECIST v1.1 as assessed by BICR","definition_or_measurement_approach":"Duration of response per RECIST v1.1 assessed by Blinded Independent Central Review (BICR)"}
• {"endpoint_text":"- DOR using RECIST v1.1 as assessed by investigator","definition_or_measurement_approach":"Duration of response per RECIST v1.1 assessed by investigator"}
• {"endpoint_text":"- Type, incidence, severity, seriousness, and relatedness of adverse events (AEs)","definition_or_measurement_approach":"Safety endpoints: adverse event reporting (type, incidence, severity, seriousness, relatedness)"}
• {"endpoint_text":"- Plasma concentration at end of infusion (CEOI) and Plasma predose concentration (Cpredose) for antibody conjugated monomethyl auristatin E (ac-MMAE) and unconjugated monomethyl auristatin E (MMAE)","definition_or_measurement_approach":"Pharmacokinetic measures: CEOI and Cpredose for ac-MMAE and MMAE"}
• {"endpoint_text":"- Incidence of antidrug antibodies (ADAs)","definition_or_measurement_approach":"Incidence of anti-drug antibodies measured by immunogenicity assays"}

Methods

• Global website recruitment materials (Global Website) — digital channel; intended for potential participants; multi-country use (documents listed per country).
• Study brochure — printed/digital brochure for potential participants (country-specific brochures present).
• Study poster — site posters for patient-facing recruitment (country-specific posters present).
• QR code cards — digital quick-access recruitment (country-specific materials present).
• Digital media board — digital on-site/digital signage recruitment mockups.
• Social media mockups (Global Facebook Mockup) — digital/social media recruitment.
• Site recruitment material (site-specific brochures/advocacy cards) — HCP/patient facing materials distributed at sites.
• HCP brochure / Investigator-facing recruitment material — materials for healthcare professionals to support recruitment.

Primary sponsor

Full Name

Pfizer Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Icon Clinical Research Limited

Responsibilities

Firecrest - Training and document portal

Name

Iqvia Pharma Inc.

Responsibilities

OUS onsite Recruitment support; Clinical Trial Educator support

Name

WCG Clinical Inc.

Responsibilities

Site Resource Support with assigned CRC - Data entry & query resolution - Referral network support and recruitment

Third parties

• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"ePRO and EDC Data Collection","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Iqvia Pharma Inc.","duties_or_roles":"OUS onsite Recruitment support; Clinical Trial Educator support","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"Discovery Life Sciences Biomarker Services GmbH","duties_or_roles":"Laboratory assessment","organisation_type":"Pharmaceutical company"}
• {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"Firecrest - Training and document portal","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Clario Medical Imaging Inc.","duties_or_roles":"Central Imaging","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Q Squared Solutions LLC","duties_or_roles":"","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Sitero LLC","duties_or_roles":"Investigator Payment","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Frontage Laboratories Inc.","duties_or_roles":"Sample management","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Cognizant Worldwide Limited","duties_or_roles":"Shared Investigator Platform","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Guardant Health Inc.","duties_or_roles":"Laboratory assessment","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"ePRO and EDC Data collection","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"WCG Clinical Inc.","duties_or_roles":"Site Resource Support with assigned CRC - Data entry & query resolution - Referral network support and recruitment","organisation_type":"Pharmaceutical company"}