| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| First Line Non-Small Cell Lung Cancer |
|
| E.1.1.1 | Medical condition in easily understood language |
| First Line Non-Small Cell Lung Cancer |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| MedDRA Classification |
| 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 |
To evaluate the efficacy of zimberelimab (AB122) monotherapy compared to platinum-doublet chemotherapy.
To evaluate the efficacy of zimberelimab and domvanalimab combination therapy compared to zimberelimab monotherapy (Arm B vs. Arm C) |
|
| E.2.2 | Secondary objectives of the trial |
To evaluate the clinical activity of zimberelimab monotherapy in participants who crossed over from platinum-doublet chemotherapy.
To evaluate the efficacy of zimberelimab monotherapy compared to platinum-doublet chemotherapy, or to zimberelimab and domvanalimab combination therapy on quality of life / health status.
To assess the safety of zimberelimab monotherapy compared to platinum-doublet chemotherapy, or to zimberelimab and domvanalimab combination therapy. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Male or female participants; age ≥ 18 years, or age ≥ regionally approved age of consent for participation in investigational clinical studies, at the time of prescreening.
2. Willing and able to comply with the requirements and restrictions in this protocol.
3. Histologically confirmed, treatment naïve, locally advanced or metastatic (stage IIIB ─ IV per AJCC version 8), squamous or non-squamous NSCLC with documented high PD-L1 expression (TPS ≥ 50% by PharmDx 22C3 IHC assay as assessed by central laboratories).
a. Patients with locally advanced disease must not be eligible to receive other potentially curative therapies.
b. Patients must be treatment naïve with respect to locally advanced or metastatic disease. Patients who received prior treatment with curative intent for early stage disease must have completed treatment at least 6 months prior to first dose of IP.
4. In regions where immune checkpoint inhibitors are approved as standard treatment, patients must not have access to and must decline treatment with locally approved immune checkpoint inhibitor.
5.ECOG PS of 0-1
6. At least 1 measurable target lesion per RECIST v1.1
7. Adequate organ and marrow function, as defined below:
a. Neutrophils ≥ 1500/μL
b. Platelets ≥ 100 x 103/μL
c. Hemoglobin ≥ 9.0 g/dL
d. Aspartate aminotransferase ≤ 2.5 x upper limit of normal (ULN) without hepatic metastasis and ≤ 5 x ULN with hepatic metastasis
e. Alanine aminotransferase ≤ 2.5 x ULN without hepatic metastasis and ≤ 5 x ULN with hepatic metastasis
f. Bilirubin ≤ 2 x ULN (except participants with Gilbert’s syndrome who must have total bilirubin < 3.0 mg/dL)
g. Creatinine ≤ 2 x ULN or calculated creatinine clearance (CrCl) > 45 mL/min. CrCl can be calculated using the Cockroft-Gault method
8. If a participant has brain or meningeal metastases, the participant must meet the following criteria:
a. Have no evidence of progression by neurologic symptoms or sign for at least 4 weeks prior to the first dose.
b. Metastatic brain lesions do not require immediate intervention.
c. Carcinomatous meningitis is excluded regardless of clinical stability.
9. Women of childbearing potential (WOCBP), defined as not surgically sterilized and between menarche and 1-year post menopause, must have a negative serum pregnancy test.
10. WOCBP and male participants with WOCBP sexual partners must agree to the contraception, guidelines according to Section 6.5.2.
11. Female participants must not be breast feeding. |
|
| E.4 | Principal exclusion criteria |
1. Presence of ALK fusion oncogene or EGFR mutation. Patients with unknown ALK or EGFR status and non-squamous histology must be tested centrally at prescreening if previous results are not available.. Note: EGFR and ALK mutational testing is not required for patients with squamous histology.
2. Presence of any other tumor genomic aberration or driver mutation (eg, ROS, BRAF, NTRK) for which a targeted therapy is approved by local health authority and available.
3.Use of any live vaccines against infectious diseases within 28 days of first dose of IP(s).
4. History of trauma or major surgery within 28 days prior to the first dose of IP. (Note that placement of central venous access catheter (eg, port or similar) is not considered a major surgical procedure).
5. Underlying medical conditions that, in the Investigator’s or Sponsor’s opinion, will make the administration of IP(s) hazardous, including but not limited to
a. Interstitial lung disease, including history of interstitial lung disease or non-infectious pneumonitis,
b. Active viral, bacterial or fungal infections requiring parenteral treatment within 14 days of the initiation of the IP,
c. Clinically significant cardiovascular disease,
d. A condition that may obscure the interpretation of toxicity determination or AEs,
e. History of prior solid-organ transplantation.
6. Concurrent medical condition requiring the use of supra-physiologic doses of corticosteroids (> 10 mg/day of oral prednisone or equivalent) or immunosuppressive medications (absorbable topical corticosteroids are not excluded).
7. Positive test results for hepatitis B surface antigen, hepatitis C virus antibody with presence of hepatitis C qualitative RNA or human immunodeficiency virus antibody (HIV-1 and/or HIV-2) at screening.
8. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
9. Has significant dementia or other mental condition that precludes the participant’s ability to consent to the study.
10. Any active autoimmune disease or a documented history of autoimmune disease or syndrome that required systemic treatment in the past 2 years (ie, with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs), except for vitiligo or resolved childhood asthma/atopy.
a. Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment.
b. Participants with asthma who require intermittent use of bronchodilators, inhaled corticosteroids, or local corticosteroid injections will not be excluded from this study. Participants on chronic systemic corticosteroids will be excluded from the study.
11. Prior malignancy active within the previous 2 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix, breast, or prostate cancer.
12. Prior treatment with any anti-PD-1, anti-PD-L1 or any other antibody targeting an immune checkpoint.
13. Use of other investigational drugs (drugs not marketed for any indication) within 28 days or 5 half-lives (whichever is longer) of first dose of IP.
14. Known hypersensitivity to recombinant proteins, or any excipient contained in the IP formulations. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Progression-free survival (PFS) according to RECIST v1.1, as assessed by the investigator
Overall survival (OS)
|
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Throughout study duration |
|
| E.5.2 | Secondary end point(s) |
PFS according to RECIST v1.1 as assessed by the investigator, and OS at milestone timepoints.
Overall response rate (ORR) according to RECIST v1.1 as assessed by the investigator.
Presence of treatment-emergent adverse events.
Changes in vital signs and clinical laboratory parameters . |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Throughout study duration |
|
| 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 | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| 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) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| 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 | 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 | 5 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 12 |
| 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 |
| Bangladesh |
| Brazil |
| Hong Kong |
| India |
| Korea, Republic of |
| Malaysia |
| Mexico |
| Peru |
| Philippines |
| South Africa |
| Taiwan |
| Thailand |
| United States |
| Viet Nam |
| Switzerland |
| Bosnia and Herzegovina |
| Turkey |
| Serbia |
| Belgium |
| Denmark |
| France |
| Greece |
| Ireland |
| Italy |
| Netherlands |
| Poland |
| Portugal |
| Romania |
| Slovakia |
| Spain |
| Sweden |
| United Kingdom |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| 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
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 6 |
| E.8.9.1 | In the Member State concerned months | 6 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 6 |
| E.8.9.2 | In all countries concerned by the trial months | 6 |
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