| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| locally advanced or metastatic NSCLC |
|
| E.1.1.1 | Medical condition in easily understood language |
| Non-small cell lung cancer (NSCLC) |
|
| 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 | 10029521 |
| E.1.2 | Term | Non-small cell lung cancer stage IIIB |
| 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 | 10029522 |
| E.1.2 | Term | Non-small cell lung cancer stage IV |
| 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 | 10059515 |
| E.1.2 | Term | Non-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 |
| For sub-study specific objectives and endpoints, refer to each respective sub-study appendix of Protocol Amendment 4. For Sub-Study A, refer to Section 12.3; for Sub-Study B, refer to Section 13.3. |
|
| E.2.2 | Secondary objectives of the trial |
| For sub-study specific objectives and endpoints, refer to each respective sub-study appendix of Protocol Amendment 4. For Sub-Study A, refer to Section 12.3; for Sub-Study B, refer to Section 13.3. |
|
| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Sub-study A - the objectives are listed in E2.1 and E2.2 of this application form
Sub-study B - the objectives are listed in E2.1 and E2.2 of this application form |
|
| E.3 | Principal inclusion criteria |
Phase 1b and Phase 2 for All Sub Studies:
Age and Sex:
• Male or female participants age ≥18 years at Screening (except in Japan, where participants must be ≥20 years).
• Male and female participants must agree to contraceptive use
• Female participants of childbearing potential must have negative serum pregnancy or urine pregnancy test at Screening.
Type of Participant and Disease Characteristics:
• Documented histologically or cytologically confirmed locally advanced/metastatic (Stage IIIB IV) NSCLC, per AJCC/ International Union for Cancer Control TNM system, 7th edition. For Stage IIIB disease relapse during treatment or within 6 months following adjuvant therapy will be considered metastatic disease. In addition, for Stage IIIB, must not be amenable for definitive therapy (eg, surgery or chemoradiation).
• At least 1 measurable lesion per RECIST v1.1 at Screening.
• ECOG Performance Status 0 or 1.
• Resolved acute effects of any prior therapy to baseline severity or CTCAE Grade ≤1 unless otherwise specified
• Life expectancy ≥3 months as assessed by the investigator for previously treated participants or ≥12 months for first-line untreated participants.
• Adequate bone marrow function (without hematopoietic growth factor or transfusion support within 14 days prior to first dose of study intervention), including:
a. Absolute neutrophil count ≥1500/mm3 or ≥1.5 × 109/L;
b. Platelets ≥100,000/mm3 or ≥100 × 109/L;
c. Hemoglobin ≥9 g/dL (may have been transfused).
• Adequate renal function, defined by:
Estimated creatinine clearance ≥30 mL/min according to the Cockcroft-Gault formula or by 24 hour urine collection for creatinine clearance, or according to local institutional standard method.
• Adequate liver function, including:
a. Total serum bilirubin ≤1.5 × ULN unless the participant has documented Gilbert syndrome;
b. AST and ALT ≤2.5 × ULN; ≤5.0 × ULN if there is liver involvement by the tumor;
c. Alkaline phosphatase ≤2.5 × ULN (≤5 × ULN in case of bone metastasis).
• Additional inclusion criteria for sub-study A are listed in Protocol section 12.5.1
• Additional inclusion criteria for sub-study B are listed in Protocol section 13.5.1
|
|
| E.4 | Principal exclusion criteria |
Phase 1b and Phase 2 for All Sub Studies:
Medical Conditions:
• Active or prior autoimmune disease that might deteriorate when receiving an immunostimulatory agent. Participants with diabetes type I, vitiligo, psoriasis, or hypothyroid or hyperthyroid disease not requiring immunosuppressive treatment are eligible.
• Previous Grade ≥3 irAE; or unresolved irAEs prior to first dose of study intervention.
• Active, non-infectious pneumonitis, pulmonary fibrosis, or known history of immune-mediated pneumonitis.
• Active infection requiring systemic therapy.
• Clinically significant cardiovascular diseases, including any of the following:
a) History of acute myocardial infarction, acute coronary syndromes (including unstable angina, coronary artery bypass graft, coronary angioplasty or stenting)
≤6 months prior to start of study treatment;
b) Congestive heart failure requiring treatment (New York Heart Association Class ≥2);
c) Uncontrolled hypertension defined as persistent systolic blood pressure ≥150 mmHg or diastolic blood pressure ≥100 mmHg despite optimal therapy;
d) History or presence of clinically significant or uncontrolled sustained cardiac arrhythmias (including uncontrolled atrial fibrillation or uncontrolled paroxysmal supraventricular tachycardia);
e) History of thromboembolic or cerebrovascular events ≤3 months prior to the first dose of study treatment. Examples include transient ischemic attacks, cerebrovascular accidents, hemodynamically significant (ie, massive or sub massive) deep vein thrombosis or pulmonary emboli.
Note: Participants with either deep vein thrombosis or pulmonary emboli that do not result in hemodynamic instability are allowed to enroll as long as they are stable, asymptomatic and on stable anticoagulants for at least 2 weeks.
Note: Participants with thromboembolic events related to indwelling catheters or other procedures may be enrolled.
• Other malignancy within 2 years prior to the first dose of study intervention, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the breast or of the cervix, or low-grade (Gleason 6 or below) prostate cancer on surveillance without any plans for treatment intervention (eg, surgery, radiation, or castration) or other concurrent malignancy investigator feels has a very low likelihood to become metastatic.
• Clinically significant multiple or severe drug allergies, intolerance to topical corticosteroids, or severe post-treatment hypersensitivity reactions (including, but not limited to, erythema multiforme major, linear immunoglobulin A [IgA] dermatosis, toxic epidermal necrolysis, and exfoliative dermatitis.
• Symptomatic brain metastasis: participants previously treated for this condition or untreated with brain metastases <10 mm without associated edema, who are asymptomatic in the absence of corticosteroid therapy are allowed.
• Leptomeningeal disease.
• Known history of acute or chronic pancreatitis.
• Concurrent neuromuscular disorder that is associated with the potential of elevated CK (eg, inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy).
• Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator’s judgment, make the participant inappropriate for the study.
• Participants with active, uncontrolled bacterial, fungal, or viral infection, including HBV, HCV, or known HIV infection. If HIV infection status is unknown, testing for HIV must be performed at sites where mandated locally.
Prior/Concomitant Therapy:
• Live attenuated vaccines within 4 weeks prior to first dose of study intervention and while on study treatment.
• Major surgery or received radiation therapy within 2 weeks prior to first dose of study intervention.
Other Exclusions:
• Investigator site staff or Pfizer employees directly involved in the conduct of the study, site staff otherwise supervised by the investigator, and their respective family members.
Additional exclusion criteria for sub-study A criteria are detailed in Protocol section 12.5.2.
Additional exclusion criteria for sub-study B criteria are detailed in Protocol section 13.5.2. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| For sub-study specific objectives and endpoints, refer to each respective sub-study appendix. For Sub-Study A, refer to Section 12.3; for Sub-Study B, refer to Section 13.3. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Timepoint of evaluation for the secondary endpoints differs for each endpoint |
|
| E.5.2 | Secondary end point(s) |
| For sub-study specific objectives and endpoints, refer to each respective sub-study appendix of Protocol Amendment 4. For Sub-Study A, refer to Section 12.3; for Sub-Study B, refer to Section 13.3. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Timepoint of evaluation for the secondary endpoints differs for each endpoint |
|
| 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 | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | Yes |
| E.6.11 | Pharmacogenomic | Yes |
| E.6.12 | Pharmacoeconomic | Yes |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
|
| 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) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | No |
| E.8.1.1 | Randomised | No |
| 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 | Yes |
| E.8.1.7.1 | Other trial design description |
| umbrella study with sub-studies in parallel |
|
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 3 |
| 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 | 9 |
| 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 |
| Australia |
| Belgium |
| Canada |
| Germany |
| Netherlands |
| Russian Federation |
| Taiwan |
| Turkey |
| United Kingdom |
| United States |
|
| 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 the study is defined as the date of study completion for the last participant in the trial globally, at sponsor discretion if the data support ending the study, or 3 years after first dose of the last participant, whichever is earlier. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 3 |
| E.8.9.1 | In the Member State concerned days | 25 |
| E.8.9.2 | In all countries concerned by the trial years | 3 |
| E.8.9.2 | In all countries concerned by the trial months | 11 |
| E.8.9.2 | In all countries concerned by the trial days | 20 |
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