| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Non-small cell lung cancer (NSCLC) |
|
| E.1.1.1 | Medical condition in easily understood language |
| NSCLC is a lung cancer that has spread to areas near the lungs or other organs |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 21.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10061873 |
| E.1.2 | Term | Non-small cell lung cancer |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 21.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10059514 |
| E.1.2 | Term | Small cell lung cancer metastatic |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
Part 1: Dose Finding
• To determine the dose of atezolizumab subcutaneous (SC) that is predicted to yield drug exposure that is comparable to that of atezolizumab IV
Part 2: Dose Confirmation
• To demonstrate non-inferiority of exposure to atezolizumab SC compared with atezolizumab IV
|
|
| E.2.2 | Secondary objectives of the trial |
Part 1
• To characterize the PK profile of atezolizumab SC
Part 1 and Part 2
• To evaluate the safety of atezolizumab SC
Part 2
• To evaluate the efficacy of atezolizumab SC
• To characterize the PK profile of atezolizumab SC compared with atezolizumab IV
• To evaluate patient experience with atezolizumab SC compared with atezolizumab IV
• To evaluate the incidence of ADAs to the tested molecules
• To evaluate health care professional (HCP) reported experience with administration of atezolizumab SC and atezolizumab IV
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Applicable to both Parts 1 and 2
- Age >=18 years
- Ability to comply with the study protocol, in the investigator's judgment
- Measurable disease as defined by RECIST v1.1
- Eastern cooperative oncology group performance status of 0 or 1
- Life expectancy >=12 weeks
- Adequate hematologic and end-organ function
- Negative HIV test at screening
- Negative hepatitis B surface antigen (HBsAg) test at screening
- Negative total hepatitis B core antibody (HBcAb) test, or positive total HBcAb test followed by a negative hepatitis B virus (HBV) DNA test at screening
- Negative hepatitis C virus (HCV) antibody test, or positive HCV antibody test followed by a negative HCV RNA test at screening
- For patients receiving therapeutic anticoagulation: stable anticoagulant regimen
- For women of childbearing potential: agreement to remain abstinent or use contraceptive methods, and agreement to refrain from donating eggsduring the treatment period and for 5 months after the final dose of atezolizumab and for 6 months after the last dose of bevacizumab, carboplatin, or paclitaxel
- Patients must have recovered from all acute toxicities from previous therapy, excluding alopecia
- Intact normal skin without potentially obscuring tattoos, pigmentation, or lesions in the area for intended injection in the thighs
- For patients randomized in the extended China enrollment phase at qualified sites: current resident of mainland China, Hong Kong, or Taiwan, and of Chinese ancestry
Additional inclusion criteria applicable to Part 1 only
- A body mass index between 18 and 32 kg/m2 inclusive
Additional inclusion criteria applicable to Part 2 only
- For patients whose tumor may harbor a sensitizing EGFR mutation, known EGFR test results at the time of randomization
- Availability of a pre-study treatment representative formalin-fixed paraffin-embedded (FFPE) tumor specimen in paraffin block (preferred) or at least six slides, from an FFPE tumor specimen
|
|
| E.4 | Principal exclusion criteria |
Applicable to both Parts 1 and 2
- Symptomatic, untreated, or actively progressing CNS metastases
- Spinal cord compression not definitively treated with surgery and/or radiation, or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for >=2 weeks prior to enrollment
- History of leptomeningeal disease
- Uncontrolled pleural effusion or symptomatic hypercalcemia, pericardial effusion, or ascites requiring recurrent drainage procedures
- History of malignancy other than NSCLC within 5 years prior to screening
- History of severe anaphylactic reactions to chimeric or humanized antibodies or fusion proteins
- Known hypersensitivity to Chinese hamster ovary cell products or any component of the atezolizumab formulation
- Active or history of autoimmune disease or immune deficiency or tuberculosis
- History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography scan
- Current treatment with anti-viral therapy for HBV
- Severe infection within 4 weeks prior to initiation of study treatment
- Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment
- Significant cardiovascular disease, within 3 months prior to initiation of study treatment
- Major surgical procedure, other than for diagnosis, within 4 weeks prior to initiation of study treatment, or anticipation of need for a major surgical procedure during the course of the study
- Prior allogeneic stem cell or solid organ transplantation
- Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during atezolizumab treatment or within 5 months after the final dose of atezolizumab
- Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, or that may affect the interpretation of the results, or may render the patient at high risk from treatment complications
Related to Medications
- Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti TIGIT, anti−PD-1, and anti−PD-L1 therapeutic antibodies
- Treatment with systemic immunostimulatory agents within 4 weeks or 5 half-lives of the drug and systemic immunosuppressive medication within 2 weeks prior to initiation of study treatment
- Known allergy or hypersensitivity to hyaluronidase, bee or vespid venom, or any other ingredient in the formulation of rHuPH20
Applicable to Part 1 Only
- Pathology that could interfere with any protocol-specified outcome assessment
Applicable to Part 2 Only
- Tested tumor PD-L1 expression status with an intention to treat the patient if positive
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Part 1 and 2
1. Serum concentration (Ctrough) of atezolizumab SC at Cycle 1
Part 2 (co-primary endpoint)
2. Model-predicted area under the atezolizumab concentration time curve (AUC) from 0 to 21 days (AUC[0–21 d]) at Cycle 1
|
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. Predose of Cycle 2
2. At Cycles 1- 4, 8, 12, and 16 and at treatment discontinuation visit |
|
| E.5.2 | Secondary end point(s) |
Part 1
1. Serum atezolizumab concentration at specified timepoints during SC administration
Part 1 and 2
2. Incidence and severity of adverse events, with severity determined according to National cancer institute common terminology criteria for adverse events version 5.0
3. Incidence and severity of targeted vital signs
4. Incidence and severity of clinical laboratory abnormalities
Part 2
5. Model-predicted Ctrough at Cycle 1 (Ctrough cycle 1), model-predicted Ctrough at steady state (Ctrough,ss), and model-predicted AUC at steady state (AUCss)
6. Overall patient-reported adverse event burden over time
7. Objective Response Rate
8. Progression-Free Survival
9. Overall Survival
10. Duration of response
11. Functioning and global health status over time, as assessed by the physical functioning, role functioning, and global health status/quality of life scales of the European Organisation for Research and Treatment of Cancer IL57
12. Overall satisfaction with treatment, as assessed by the modified satisfaction with therapy scale of the Cancer Therapy Satisfaction Questionnaire
13. Incidence of ADAs to atezolizumab after SC administration or IV administration relative to the prevalence of ADAs at baseline
14. Incidence of ADAs to rHuPH20 after SC administration relative to the prevalence of ADAs at baseline
15. Convenience, potential time savings, and overall satisfaction with atezolizumab SC compared with atezolizumab IV, as assessed by the HCP SC versus IV Perspective Questionnaire
16. Convenience, ease of administration, and overall satisfaction with atezolizumab SC, as assessed by the HCP Subcutaneous Perspective Questionnaire
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. At Cycles 1- 4, 8, 12, and 16 and at treatment discontinuation visit
2-4. Up to 5.3 years
5. At Cycles 1- 4, 8, 12, and 16 and at treatment discontinuation visit
6-10. Up to 5.3 years
11. Day 1 of Cycles 1-6, every even numbered cycle thereafter during study treatment, and at the treatment discontinuation visit
12. At Cycle 3, or at the treatment discontinuation visit
13-14. At Cycles 1- 4, 8, 12, and 16 and at treatment discontinuation visit
15-16. Up to 5.3 years
|
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | Yes |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | Yes |
| E.7.1.3.1 | Other trial type description |
|
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 6 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 24 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Argentina |
| Brazil |
| Chile |
| China |
| Costa Rica |
| Guatemala |
| Mexico |
| New Zealand |
| Peru |
| South Africa |
| Thailand |
| Russian Federation |
| Turkey |
| Ukraine |
| France |
| Greece |
| Hungary |
| Italy |
| Latvia |
| Poland |
| Spain |
| Korea, Republic of |
| United Kingdom |
|
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
| The end of this study is defined as the date when the last data point required for statistical analysis or safety follow-up is received from the last patient (or when all patients have died or the trial is terminated by the Sponsor, whichever is earliest). |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 5 |
| E.8.9.1 | In the Member State concerned months | 4 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 5 |
| E.8.9.2 | In all countries concerned by the trial months | 4 |
Print
