Health Condition 1: C349- Malignant neoplasm of unspecifiedpart of bronchus or lung
Conditions
Interventions
Intervention1: Experimental Arm
Rilvegostomig: rilvegostomig 750 mg iv Q3W in combination with
carboplatin AUC 6 iv Q3W and paclitaxel 200 mg/m2 iv Q3W or nab-paclitaxel
100 mg/m2 iv Day 1, 8, and 15
Sponsors
AstraZeneca AB
AstraZeneca Pharma India Ltd
Eligibility
Inclusion criteria
Inclusion criteria: Inclusion criteria Participants are eligible to be included in the study only if all of the following criteria apply 1. Participant must be greater than or equal 18 at the time of signing the ICF. 2.Histologically or cytologically documented squamous NSCLC. 3.Stage IV mNSCLC (based on the American Joint Committee on Cancer Edition 8) not amenable to curative treatment. 4.Absence of documented tumor genomic mutation results from tests conducted as part of standard local practice in any actionable driver oncogenes for which there are locally approved targeted 1L therapies. 5.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. 6.Minimum life expectancy of 12 weeks. 7.Provision of acceptable tumor sample, as defined in the Pathology Manual and Laboratory Manual and summarized in Section 8.8, to confirm tumor PD-L1 expression TC greater than or equal 1% using the VENTANA PD-L1 (SP263) Assay at a Sponsor-designated central laboratory prior to randomization. Participants with unknown PD-L1 status or TC lesser than1% are not eligible for the study. 8.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 greater than or equal 10 mm in the longest diameter (except lymph nodes, which must have short axis greater than or equal 15 mm) with CT or MRI and is suitable for accurate repeated measurements. 9. Adequate organ and bone marrow function as defined in below table. 10. Minimum body weight of 30 kg. 11. Contraceptive use by participants should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. 12. 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 blinded study treatment and 6 months after last dose of chemotherapy. (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 blinded study treatment and 6 months after last dose of chemotherapy. 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 blinded study treatment and 6 months after last dose of chemotherapy. 13. 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 blinded study treatment and 6 months after last dose of chemotherapy. Periodic abstinence, the rhythm method, and the withdrawal method are not acceptab
Exclusion criteria
Exclusion criteria: Exclusion criteria Participants are excluded from the study if any of the following criteria apply Medical Conditions 1. As judged by the investigator, any severe or uncontrolled systemic diseases, including, but not limited to, uncontrolled hypertension, and active bleeding diseases, ongoing or active known infection; ILD (of any grade), serious chronic gastrointestinal conditions associated with diarrhea (eg, active inflammatory bowel disease), active non-infectious skin disease (including any grade rash, urticaria, dermatitis, ulceration, or psoriasis) requiring systemic treatment, psychiatric illness/social situations, substance abuse, or significant cardiac conditions which, in the investigator s opinion, makes it undesirable for the participant to participate in the study or that would jeopardize compliance with the protocol. 2. History of organ transplant. 3. Active or prior documented autoimmune or inflammatory disorders requiring chronic treatment with steroids or other immunosuppressive treatment. 4. History of another primary malignancy except for malignancy treated with curative intent with no known active disease greater than or equal 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. 5. Presence of small cell and neuroendocrine histology components. 6. Persistent toxicities (CTCAE Grade greater than or equal 2) caused by previous anticancer therapy, excluding alopecia. Participants may be enrolled with the following chronic stable Grade 2 toxicities (defined as no worsening to greater than Grade 2 for at least 3 months prior to the first dose of study intervention and managed with SoC treatment) which the investigator deems related to previous anticancer therapy: (a) Chemotherapy-induced neuropathy. (b) Fatigue. (c) Vitiligo. (d) Endocrine disorders, that are controlled with replacement hormone therapy. (e) Participants with irreversible toxicity that is not reasonably expected to be exacerbated by study intervention in the opinion of the investigator may be included (eg, hearing loss). 7. Spinal cord compression. 8. Brain metastases unless asymptomatic, stable, and not requiring steroids or anticonvulsants for at least 4 weeks prior to start of study intervention. A minimum of 2 weeks must have elapsed between the end of brain radiotherapy and study enrollment. Participants must have recovered from the acute toxic effect of radiotherapy (eg, dizziness and signs of increased intracranial pressure). 9. Active primary immunodeficiency/active infectious disease(s) Known active hepatitis A, chronic or active hepatitis B, or chronic or active hepatitis C infection Participants who have chronic HBV and are receiving suppressive antiviral therapy are allowed to be enrolled if viral load is controlled and ALT is normal. Those with ALT lesser than 3 ULN (in presence of liver metastases), not attributable to HBV infection and with controlled viral load could be enrolled. Controlled hepatitis B viral load is defined as serum HBV DNA lesser than 100 U/mL by PCR. Participants with controlled hepatitis B viral load must remain on antiviral therapy, per institutional practice, during the study treatment and follow-up period to ensure adequ
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To demonstrate the efficacy of rilvegostomig plus chemotherapy relative to pembrolizumab plus chemotherapy by assessment of OS To demonstrate the efficacy of rilvegostomig plus chemotherapy relative to pembrolizumab plus chemotherapy by assessment of PFSTimepoint: OS is defined as the time from randomization until the date of death due to any cause. The analysis will include all randomized participants. All deaths will be included regardless of whether the participant withdraws from therapy or receives another anticancer therapy. The measure of interest is the HR of OS PFS is defined as the time from randomization until radiological progression per RECIST 1.1 as assessed by BICR, or death due to any cause (in the absence of progression). The analysis will include all randomized participants. All events will be included regardless of whether the participant withdraws from therapy, receives another anticancer therapy or clinically progresses prior to radiographic progression per RECIST 1.1. However, if the participant progresses or dies immediately after 2 or more consecutive missed visits, the participant will be censored at the time of the latest evaluable assessment prior to the 2 missed visits. The measure of interest is the HR of PFS. | — |
Secondary
| Measure | Time frame |
|---|---|
| To characterize the efficacy of rilvegostomig plus chemotherapy relative to pembrolizumab plus chemotherapy by assessment of OSTimepoint: OS is defined as the time from randomization until the date of death due to any cause. The analysis will include all randomized participants. All deaths will be included regardless of whether the participant withdraws from therapy or receives another anticancer therapy. The measures of interest are the landmark OS rates at 12, 24, 36, and 48 months ;To characterize the efficacy of rilvegostomig plus chemotherapy relative to pembrolizumab plus chemotherapy by assessment of PFSTimepoint: PFS is defined as the time from randomization until radiological progression per RECIST 1.1 as assessed by BICR, or death due to any cause (in the absence of progression). The analysis will include all randomized participants. All events will be included regardless of whether the participant withdraws from therapy, receives another anticancer therapy, or clinically progresses prior to radiographic progression per RECIST 1.1. However, if the participant progresses or dies immediately after 2 or more consecutive missed visits, the participant will be censored at the time of the latest evaluable assessment prior to the 2 missed visits. The measures of interest are the landmark PFS rates at 12, 24, and 36 months. ;To compare the efficacy of rilvegostomig plus chemotherapy relative to pembrolizumab plus chemotherapy by assessment of PFS2Timepoint: PFS2 is defined as the time from randomization until the earliest of the progression event (following the initial investigator-assessed progression event), after the start of the first subsequent therapy, or death from any cause, whichever occurs first. The date of the second progression will be recorded by the investigator in the eCRF and defined according to local standard clinical practice. The analyses will include all randomized participants. All events will be included, regardless of whether the pa | — |
Countries
Argentina, Australia, Austria, Belgium, Belize, Canada, China, France, Germany, Hungary, India, Israel, Italy, Japan, Malaysia, Netherlands, Peru, Poland, Republic of Korea, Spain, Taiwan, Thailand, Turkey, United Kingdom, United States of America, Viet Nam
Contacts
Public ContactMr Sandeep AV
AstraZeneca Pharma India Ltd
Outcome results
None listed