C349 Bronchus or lung, unspecified Bronchus or lung, unspecified
Conditions
Interventions
Participants in the Dato-DXd in combination with durvalumab and carboplatin group will receive Dato-DXd 6.0 mg/kg plus durvalumab 1120 mg plus carboplatin AUC 5 mg/mL/minute as i.v. infusions Q3W on D
or ? Regimen 2 (participants with squamous NSCLC): Pembrolizumab 200 mg plus paclitaxel 200 mg/m2 plus carboplatin (AUC 5 or 6 mg/mL/minute) as i.v. infusions Q3W on Day 1 of the first 4 cycles, follo
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Age 1. Participant must be = 18 years at the time of screening. Type of Participant and Disease Characteristics 2. Histologically or cytologically documented NSCLC that: (a) Is Stage IIIB or IIIC disease not amenable for surgical resection or definitive chemoradiation, or Stage IV metastatic NSCLC disease at the time of randomisation who have not received prior chemotherapy or other systemic therapy for first-line Stage IIIB, IIIC or IV NSCLC. Participants who have received prior platinumcontaining adjuvant, neoadjuvant, or definitive chemoradiation for early stage disease (Stage I to IIIA) are eligible, provided that progression has occurred > 6 months from the last dose of checkpoint inhibitor, chemotherapy, or other systemic anti-cancer therapy. (b) Lacks sensitising EGFR tumour tissue mutation (eg, exon 19 deletion or exon 21 L858R, exon 21 L861Q, exon 18 G719X, or exon 20 S768I mutation), as well as ALK and ROS1 rearrangements. (c) Has no documented tumour genomic alteration results in NTRK, BRAF, RET, MET or any other actionable driver oncogenes for which there are locally approved and available targeted first-line therapies. Note: Participants whose tumours harbour KRAS mutations are eligible for the study. 3. ECOG PS of 0 or 1 with no deterioration over the previous 2 weeks prior to day of first dosing. 4. FFPE tumour sample collected prior to signing of informed consent, ie, the start of screening (see Section 8.6.1.1 and the Laboratory Manual for further details). 5. Tumour PD-L1 status defined as TC 40 mL/min as determined by Cockcroft-Gault (using actual body weight). Males: CrCL = Weight (kg) × (140 – Age [years]) / 72 × serum creatinine (mg/dL) (mL/min) Females: CrCL = Weight (kg) × (140 – Age [years]) × 0.85 / 72 × serum creatinine (mg/dL)
Exclusion criteria
Exclusion criteria: Medical Conditions 1 As judged by the investigator, any evidence of diseases (such as severe or uncontrolled systemic diseases, including active bleeding diseases, active infection, active ILD/pneumonitis, serious chronic gastrointestinal conditions associated with diarrhoea, psychiatric illness/social situations or significant cardiac conditions), or history of allogenic organ transplant, which, in the investigator’s opinion, makes it undesirable for the participant to participate in the study or that would jeopardise compliance with the protocol. 2 History of another primary malignancy except for malignancy treated with curative intent with no known active disease within 3 years before the first dose of study intervention and of low potential risk for recurrence, adequately resected basal cell carcinoma of the skin or squamous cell carcinoma of the skin, lentigo maligna that has undergone potentially curative therapy or adequately treated in situ disease without evidence of disease. 3 Mixed small-cell lung cancer and NSCLC histology; sarcomatoid variant of NSCLC. 4 Persistent toxicities caused by previous anti-cancer therapy, excluding alopecia or vitiligo, not yet improved to Grade = 1 or baseline. Note: participants may be enrolled with some chronic, stable Grade 2 toxicities (defined as no worsening to > Grade 2 for at least 3 months prior to randomisation and managed with SoC treatment) which the investigator deems related to previous anti-cancer therapy, including (but not limited to): ? Chemotherapy-induced neuropathy. ? Fatigue. Participants with irreversible toxicity that is not reasonably expected to be exacerbated by study intervention may be included (eg, hearing loss) after consultation with the AstraZeneca study clinical lead. 5 Active or prior documented autoimmune, connective tissue or inflammatory disorders (including inflammatory bowel disease [eg, colitis or Crohn’s disease], diverticulitis, systemic lupus erythematosus, Sjögren’s syndrome, sarcoidosis (granulomatosis with polyangiitis, Graves’ disease, rheumatoid arthritis, hypophysitis, uveitis, etc.), autoimmune pneumonitis and autoimmune myocarditis. The following are exceptions to this criterion: ? Participants with vitiligo or alopecia. ? Participants with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement. ? Any chronic skin condition that does not require systemic therapy. ? Participants without active disease in the last 5 years may be included but only after consultation with the study clinical lead. ? Participants with coeliac disease controlled by diet alone. 6 Spinal cord compression or brain metastases unless asymptomatic, stable, and not requiring steroids for at least 7 days prior to randomisation. Participants with treated brain metastases that are no longer symptomatic and who require no treatment with corticosteroids or anticonvulsants must have recovered from the acute toxic effect of radiotherapy. A minimum of 2 weeks must have elapsed between the end of radiotherapy and study enrolment. 7 History of leptomeningeal carcinomatosis. 8 Clinically significant corneal disease. 9 Known active or uncontrolled hepatitis B or C virus infection. Participants are eligible if they: (a) Have been curatively treated for hepatitis C virus infection as demonstrated clinically and by viral serologies. (b) Have received hepatitis B virus vaccination with only anti-hepatitis B virus surface antibody positivity and no clinical signs of h
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| • PFS is defined as time from randomisation until progression per RECIST 1.1 as assessed by BICR, or death due to any cause. The analysis will include all randomised participants, as randomised, regardless of whether the participant withdraws from randomised therapy, receives another anti-cancer therapy or clinically progresses prior to RECIST 1.1 progression, in the following population: ? TROP2 biomarker positive population 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. NAME OF THE RESULT: To demonstrate the superiority of Dato-DXd in combination with durvalumab and carboplatin relative to pembrolizumab in combination with platinum-based chemotherapy by assessment of PFS by BICR in first-line treatment of TROP2 biomarker positive participants with locally advanced or metastatic NSCLC PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: During the study;• OS is defined as the time from randomisation until the date of death due to any cause. The analysis will include all randomised participants, as randomised, regardless of whether the participant withdraws from randomised therapy or receives another anti-cancer therapy, in the following population: ? TROP2 biomarker positive population The measure of interest is the HR of OS. NAME OF THE RESULT: To demonstrate the superiority of Dato-DXd in combination with durvalumab and carboplatin relative to pembrolizumab in combination with platinum-based chemotherapy by assessment of OS in first-line treatment of TROP2 biomarker positive participants with locally advanced or metastatic NSCLC PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: During the study | — |
Secondary
| Measure | Time frame |
|---|---|
| • PFS is defined as time from randomisation until progression per RECIST 1.1 as assessed by BICR, or death due to any cause. The analysis will include all randomised participants, as randomised, regardless of whether the participant withdraws from randomised therapy, receives another anti-cancer therapy or clinically progresses prior to RECIST 1.1 progression, in the following population: ? TROP2 biomarker positive population 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. NAME OF THE RESULT: To demonstrate the superiority of Dato-DXd in combination with durvalumab and carboplatin relative to pembrolizumab in combination with platinum-based chemotherapy by assessment of PFS by BICR in first-line treatment of TROP2 biomarker positive participants with locally advanced or metastatic NSCLC PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: During the study;• OS is defined as the time from randomisation until the date of death due to any cause. The analysis will include all randomised participants, as randomised, regardless of whether the participant withdraws from randomised therapy or receives another anti-cancer therapy, in the following population: ? TROP2 biomarker positive population The measure of interest is the HR of OS. NAME OF THE RESULT: To demonstrate the superiority of Dato-DXd in combination with durvalumab and carboplatin relative to pembrolizumab in combination with platinum-based chemotherapy by assessment of OS in first-line treatment of TROP2 biomarker positive participants with locally advanced or metastatic NSCLC PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: During the study;• PFS is defined as time from randomisation until progression | — |
Countries
Austria, Brazil, Bulgaria, Canada, China, Denmark, France, Germany, Greece, Hungaria, India, Italy, Japan, Korea South, Mexico, Peru, Poland, Spain, Sweden, Taiwan, Turkey, United Kindgdom, United States, Vietnam
Contacts
Public ContactURSULA ISABEL RODRIGUEZ FRIAS
ASTRAZENECA PERU S.A.
Outcome results
None listed