RILVEGOSTOMIG for Non-small cell lung cancer|Metastatic non-small cell lung cancer

Inclusion criteria

• {"criterion_text":"- Participant must be ≥ 18 at the time of signing the ICF."}
• {"criterion_text":"- Adequate organ and bone marrow function"}
• {"criterion_text":"- Minimum body weight of 30 kg."}
• {"criterion_text":"- Contraceptive use by participants should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies."}
• {"criterion_text":"- Female participants of childbearing potential: (a) Must have negative pregnancy test at screening and prior to each Day 1 administration of study intervention. (b) If sexually active with a non-sterilized male partner, must use at least 1 highly effective method of birth control from screening to 4 months after the last dose of study intervention. (c) Non-sterilized male partners of female participants of childbearing potential must use a male condom plus spermicide (if not available, a male condom without spermicide is acceptable) from screening to 4 months after the last dose of study intervention. Periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of contraception. (d) Must not breastfeed and must not donate, or retrieve for their own use, ova from screening to 4 months after the last dose of study intervention."}
• {"criterion_text":"- Non-sterilized male participants who are sexually active with a female partner of childbearing potential: (a) Non-sterilized male participants who are not abstinent and intend to be sexually active with a female partner of childbearing potential must use a male condom plus spermicide (if not available, a male condom without spermicide is acceptable) from screening to 4 months after the last dose of study intervention. Periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of contraception. (b) Female partners (of childbearing potential) of a male participant also must use at least 1 highly effective method of contraception (see Appendix G of the Clinical Study Protocol) throughout their participation in the study, and until at least 4 months after their male partners last dose of study intervention. (c) Male participants must refrain from fathering a child or donating sperm during the study and for 4 months after the last dose of study intervention."}
• {"criterion_text":"- Capable of giving signed informed consent as described in Appendix A which includes compliance with the requirements and restrictions listed in the ICF and in this CSP."}
• {"criterion_text":"- Provision of signed and dated written Optional Genetic Research Information informed consent prior to collection of samples for optional genetic research that supports the Genomic Initiative."}
• {"criterion_text":"- All races, gender, and ethnic groups are eligible for this study."}
• {"criterion_text":"- Histologically or cytologically documented NSCLC, including all histological subtypes."}
• {"criterion_text":"- Stage IV mNSCLC (based on the American Joint Committee on Cancer Edition 8) not amenable to curative treatment."}
• {"criterion_text":"- Absence of sensitizing EGFR mutations (including, but not limited to, exon 19 deletion and exon 21 L858R, exon 21 L861Q, exon 18 G719X, and exon 20 S768I mutations) and ALK and ROS1 rearrangements. Negative assay result is required for all non-squamous histology subtypes."}
• {"criterion_text":"- Absence of documented tumor genomic mutation results from tests conducted as part of standard local practice in any other actionable driver oncogenes for which there are locally approved targeted 1L therapies."}
• {"criterion_text":"- WHO/ECOG performance status of 0 or 1, with no deterioration over the previous 2 weeks prior to baseline at screening and prior to randomization."}
• {"criterion_text":"- Minimum life expectancy of 12 weeks."}
• {"criterion_text":"- Tumour PDL1 expression must be confirmed prior to randomization."}
• {"criterion_text":"- At least one lesion not previously irradiated that qualifies as a RECIST 1.1 TL at baseline and can be accurately measured at baseline as ≥ 10 mm in the longest diameter (except lymph nodes, which must have short axis ≥ 15 mm) with CT or MRI and is suitable for accurate repeated measurements."}

Exclusion criteria

• {"criterion_text":"- As judged by the investigator, any severe or uncontrolled systemic diseases, makes it undesirable for the participant to participate in the study or that would jeopardize compliance with the protocol."}
• {"criterion_text":"- Active tuberculosis infection"}
• {"criterion_text":"- History of clinically significant arrhythmia, cardiomyopathy of any etiology; symptomatic congestive heart failure (as defined by New York Heart Association class ≥ 3), history of myocardial infarction within the past 6 months."}
• {"criterion_text":"- Any concomitant medication known to be associated with Torsades de pointes."}
• {"criterion_text":"- Any prior systemic therapy received for advanced or mNSCLC."}
• {"criterion_text":"- Any prior exposure to an anti-TIGIT therapy or any other anticancer therapy targeting immune-regulatory receptors or mechanisms."}
• {"criterion_text":"- Any prior treatment with an anti-PD-1 or anti-PD-L1 agent."}
• {"criterion_text":"- Any concurrent chemotherapy, radiotherapy, immunotherapy, investigational, or biologic or hormonal therapy for cancer treatment other than those under investigation in this study. Concurrent use of hormonal therapy for non-cancer-related conditions (eg, insulin for diabetes, HRT, gonadotropin-releasing hormone analogs, and bisphosphonates) is acceptable."}
• {"criterion_text":"- Palliative radiotherapy with a limited field of radiation within 2 weeks or with a wide field of radiation or to more than 30% of the bone marrow within 4 weeks, prior to the first dose of study intervention."}
• {"criterion_text":"- Major surgical procedure (excluding placement of vascular access) or significant traumatic injury within 4 weeks of the first dose of study intervention or an anticipated need for major surgery during the study."}
• {"criterion_text":"- Current or prior use of immunosuppressive medication within 14 days before the first dose of study intervention is excluded. The following are exceptions to this criterion (see Appendix I)."}
• {"criterion_text":"- History of organ transplant."}
• {"criterion_text":"- Herbal or natural products intended as treatment or prophylaxis for any type of cancer that may interfere with the activity of the study intervention are excluded, see Appendix I."}
• {"criterion_text":"- Receipt of live attenuated vaccine within 30 days prior to the first dose of study intervention."}
• {"criterion_text":"- Participation in another clinical study with a study intervention or investigational medicinal device administered in the last 12 months or the combination/comparator agent (unless the safety profile is known prior to randomization), or concurrent enrollment in another clinical study (unless the study is observational [non-interventional], or the participant is in the follow-up period of an interventional study)."}
• {"criterion_text":"- Participants with a known hypersensitivity to study intervention or any excipients of the products."}
• {"criterion_text":"- Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)."}
• {"criterion_text":"- Judgment by the investigator that the participant should not participate in the study if the participant is unlikely to comply with study procedures, restrictions, and requirements."}
• {"criterion_text":"- Previous enrollment in the present study."}
• {"criterion_text":"- For females only: Currently pregnant (confirmed with positive pregnancy test) or breast-feeding, or who are planning to become pregnant."}
• {"criterion_text":"- Female participants should refrain from breastfeeding from screening throughout the study and until 4 months after last dose of study intervention."}
• {"criterion_text":"- Active or prior documented autoimmune or inflammatory disorders requiring chronic treatment with steroids or other immunosuppressive treatment."}
• {"criterion_text":"- History of another primary malignancy except for malignancy treated with curative intent with no known active disease ≥ 2 years before the first dose of study intervention and of low potential risk for recurrence. Exceptions include adequately resected non-melanoma skin cancer and curatively treated in situ disease."}
• {"criterion_text":"- Presence of small cell and neuroendocrine histology components."}
• {"criterion_text":"- Persistent toxicities (CTCAE Grade ≥ 2) caused by previous anticancer therapy, excluding alopecia."}
• {"criterion_text":"- Spinal cord compression unless the participant received adequate local treatment. Participant must have stable neurological status for at least 2 weeks after completion of local treatment and at least 7 days have elapsed after completion of steroids prior to randomization."}
• {"criterion_text":"- Brain metastases unless asymptomatic, stable, and not requiring steroids or anticonvulsants for at least 7 days prior to randomization. A minimum of 2 weeks must have elapsed between the end of local therapy (brain radiotherapy or surgery) and randomization. Participants must have recovered from the acute toxic effect of radiotherapy or surgery (eg, dizziness and signs of increased intracranial pressure) prior to randomization."}
• {"criterion_text":"- Active primary immunodeficiency/active infectious disease(s): • Known active hepatitis A, chronic or active hepatitis B, or chronic or active hepatitis C infection: • Known HIV infection that is not well controlled. All of the following criteria are required to define an HIV infection that is well controlled: undetectable viral RNA load, CD4+ count of ≥ 350 cells/µL, no history of AIDS-defining opportunistic infection within the past 12 months, and stable for at least 4 weeks on the same anti-HIV medications."}

Primary endpoints

• {"endpoint_text":"- Overall survival (OS)","definition_or_measurement_approach":""}
• {"endpoint_text":"- Progression-free survival (PFS)","definition_or_measurement_approach":"Assessment linked to RECIST 1.1 target lesion requirements (at least one lesion qualifying as a RECIST 1.1 TL is required)"}

Secondary endpoints

• {"endpoint_text":"- Landmark overall survival (OS) rates","definition_or_measurement_approach":""}
• {"endpoint_text":"- Landmark progression-free (PFS) rates","definition_or_measurement_approach":""}
• {"endpoint_text":"- Overall response rate (ORR)","definition_or_measurement_approach":"Assessments reference RECIST 1.1 target lesion criteria in protocol inclusion; specific RECIST-based assessment is indicated by lesion requirements"}
• {"endpoint_text":"- Duration of response (DoR)","definition_or_measurement_approach":""}
• {"endpoint_text":"- Time to second progression or death (PFS2)","definition_or_measurement_approach":""}
• {"endpoint_text":"- Concentration of rilvegostomig in serum.","definition_or_measurement_approach":"PK assay measuring rilvegostomig serum concentration"}
• {"endpoint_text":"- Presence ADAs, titer, and neutralizing antibodies for rilvegostomig.","definition_or_measurement_approach":"Immunogenicity assays to detect anti-drug antibodies, titers and neutralizing antibodies"}
• {"endpoint_text":"- Proportion of participants with maintained or improved physical functioning.","definition_or_measurement_approach":"Patient-reported outcome measures (specific instrument not specified in CTIS JSON)"}
• {"endpoint_text":"- Time to deterioration (TTD) of global health status (GHS)/quality of life (QoL) and in pulmonary symptoms.","definition_or_measurement_approach":"Patient-reported outcome measures (specific instrument not specified in CTIS JSON)"}
• {"endpoint_text":"- Adverse events (AEs) (graded by CTCAE version 5.0), clinical laboratory assessments, vital signs, physical examinations, and Eastern Cooperative Oncology Group (ECOG) performance status.","definition_or_measurement_approach":"AEs graded using CTCAE v5.0; clinical labs, vital signs, exams and ECOG per protocol"}

Methods

• Patient Brochure (country-specific versions documented e.g., IE, BE, BG, PT, RO)
• Patient Online Outreach / Patient Online Outreach materials (country-specific online outreach documents documented for IE, BE, BG, PT, DE, RO, etc.)
• Patient Online/Print outreach materials and patient brochures (documents listed in CTIS document list for multiple countries)

Primary sponsor

Full Name

AstraZeneca AB

Organisation Type

Pharmaceutical company

Country Of Registered Address

Sweden

Contract research organisations

Name

Fortrea Inc.

Responsibilities

Site Startup; Clinical Ancillary Supplies Services; Clinical Monitoring; Pharmacokinetics (as listed in sponsor duties)

Name

ICON Medical Imaging

Responsibilities

Imaging

Name

Medidata Solutions Inc.

Responsibilities

code 7 (platform/vendor responsibilities listed)

Third parties

• {"country":"United States","full_name":"RWS Life Sciences Inc.","duties_or_roles":"ePRO Licensing and translations","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Signant Health LLC","duties_or_roles":"code 3","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"code 7","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Hematogenix Laboratory Services LLC","duties_or_roles":"code 4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Center For Information And Study On Clinical Research Participation Inc.","duties_or_roles":"Patient Engagement Materials","organisation_type":"Patient organisation/association"}
• {"country":"United States","full_name":"Labcorp Central Laboratory Services LP","duties_or_roles":"code 4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"ICON Medical Imaging","duties_or_roles":"Imaging","organisation_type":"Industry"}
• {"country":"United States","full_name":"Fortrea Inc.","duties_or_roles":"Site Startup; Clinical Ancillary Supplies Services; Clinical Monitoring; Pharmacokinetics; codes 1,11,12,13,15","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Ventana Medical Systems Inc.","duties_or_roles":"Diagnostic partner and manufacturer","organisation_type":"Pharmaceutical company"}