Description:
This randomized phase 2 open-label study will evaluate the safety and efficacy of
zimberelimab (AB122) monotherapy, domvanalimab (AB154) in combination with zimberelimab, and
domvanalimab in combination with zimberelimab and etrumadenant (AB928) in front-line, PD-L1
positive, metastatic non-small cell lung cancer.
Title
- Brief Title: Study to Evaluate Monotherapy and Combination Immunotherapies in Participants With PD-L1 Positive Non-small Cell Lung Cancer
- Official Title: A Phase 2 Study to Evaluate the Safety and Efficacy of AB122 Monotherapy, AB154 in Combination With AB122, and AB154 in Combination With AB122 and AB928 in Front-Line, Non-Small Cell Lung Cancer
Clinical Trial IDs
- ORG STUDY ID:
AB154CSP0002
- NCT ID:
NCT04262856
Conditions
- Non Small Cell Lung Cancer
- Nonsquamous Non Small Cell Lung Cancer
- Squamous Non Small Cell Lung Cancer
- Lung Cancer
Interventions
| Drug | Synonyms | Arms |
|---|
| Zimberelimab | AB122 | Arm 1 (zimberelimab monotherapy) |
| Domvanalimab | AB154 | Arm 2 (domvanalimab and zimberelimab combination therapy) |
| Etrumadenant | AB928 | Arm 3 (domvanalimab, zimberelimab, and etrumadenant combination therapy) |
Purpose
This randomized phase 2 open-label study will evaluate the safety and efficacy of
zimberelimab (AB122) monotherapy, domvanalimab (AB154) in combination with zimberelimab, and
domvanalimab in combination with zimberelimab and etrumadenant (AB928) in front-line, PD-L1
positive, metastatic non-small cell lung cancer.
Detailed Description
This is an open-label phase 2 study in participants with non-small cell lung cancer which
will assess the safety, efficacy and tolerability of zimberelimab as monotherapy and in
combination with other immunotherapeutics across multiple treatment arms.
Approximately 150 participants will be randomized to 1 of 3 treatment arms: 1) zimberelimab,
2) zimberelimab + domvanalimab (anti-TIGIT antibody), 3) zimberelimab + domvanalimab +
etrumadenant (dual adenosine receptor antagonist). Participants that progress on the
zimberelimab monotherapy arm may cross-over to receive the third arm combination of
zimberelimab + domvanalimab + etrumadenant.
The primary objective of this clinical study is to evaluate the efficacy of each combination
therapy by assessing: 1) objective response rate (ORR) of participants with measurable
disease by Response Evaluation Criteria in Solid Tumors (RECIST v1.1) and 2) progression free
survival (PFS).
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Arm 1 (zimberelimab monotherapy) | Experimental | Participants will receive zimberelimab monotherapy by IV infusion. | |
| Arm 2 (domvanalimab and zimberelimab combination therapy) | Experimental | Participants will receive domvanalimab in combination with zimberelimab by IV infusion. | |
| Arm 3 (domvanalimab, zimberelimab, and etrumadenant combination therapy) | Experimental | Participants will receive oral etrumadenant in combination with zimberelimab and domvanalimab by IV infusion | - Zimberelimab
- Domvanalimab
- Etrumadenant
|
Eligibility Criteria
Inclusion Criteria:
- Male or female participants; age ≥ 18 years
- Histologically confirmed squamous or nonsquamous, PD-L1 positive, NSCLC that is
metastatic without sensitizing epidermal growth factor receptor (EGFR) or anaplastic
lymphoma kinase (ALK) mutation expression
- Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
- Must have at least 1 measurable lesion per RECIST v1.1
- Adequate organ and marrow function
Exclusion Criteria:
- Use of any live vaccines against infectious diseases within 28 days of first dose
- Concurrent medical condition requiring the use of supra-physiologic doses of
corticosteroids (> 10 mg/day of oral prednisone or equivalent) or immunosuppressive
medications
- Positive test results for Hepatitis B surface antigen, Hepatitis C virus antibody or
Hepatitis C qualitative RNA or human immunodeficiency virus-1 (HIV-1) antibody
- 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.
- 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
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Objective response rate (ORR) |
| Time Frame: | From randomization until death from any cause (up to approximately 3-5 years) |
| Safety Issue: | |
| Description: | ORR as assessed by RECIST v1.1 |
Secondary Outcome Measures
| Measure: | Duration of response (DoR) |
| Time Frame: | From the date of first occurence of a documented objective response to first documentation of disease progression or death from any cause, whichever occurs first (up to approximately 3-5 years) |
| Safety Issue: | |
| Description: | DoR as assessed by RECIST v1.1 |
| Measure: | Disease control rate (DCR) |
| Time Frame: | From the date of first occurence of a documented objective response to first documentation of disease progression on death from any cause, whichever occurs first (up to approximately 3-5 years) |
| Safety Issue: | |
| Description: | DCR as assessed by RECIST v1.1 |
| Measure: | Adverse Events |
| Time Frame: | From Screening until up to 100 days after the last dose (approximately 2 years) |
| Safety Issue: | |
| Description: | The number and percentage of participants that experience an adverse event (AE) |
| Measure: | Pharmacodynamics of zimberelimab |
| Time Frame: | Collected during all treatment cycles (each cycle is 21 or 28 days), up to 14 days post last dose, 30, 60 and 100 days post last dose (in total, an average of 2 years). |
| Safety Issue: | |
| Description: | Plasma concentration of zimberelimab |
| Measure: | Pharmacodynamics of domvanalimab |
| Time Frame: | Collected during all treatment cycles (each cycle is 21 or 28 days), up to 14 days post last dose, 30, 60 and 100 days post last dose (in total, an average of 2 years). |
| Safety Issue: | |
| Description: | Plasma concentration of domvanalimab |
| Measure: | Pharmacodynamics of etrumadenant |
| Time Frame: | Collected during all treatment cycles (each cycle is 21 or 28 days), up to 14 days post last dose, 30, 60 and 100 days post last dose (in total, an average of 2 years). |
| Safety Issue: | |
| Description: | Plasma concentration of etrumadenant |
| Measure: | Immunogenicity of zimberelimab |
| Time Frame: | Collected during all treatment cycles (each cycle is 21 or 28 days), up to 14 days post last dose, 30, and 100 days post last dose (in total, an average of 2 years). |
| Safety Issue: | |
| Description: | Percentage of participants who develop treatment-emergent anti-drug antibodies to zimberelimab |
| Measure: | Immunogenicity of domvanalimab |
| Time Frame: | Collected during all treatment cycles (each cycle is 21 or 28 days), up to 14 days post last dose, 30, and 100 days post last dose (in total, an average of 2 years). |
| Safety Issue: | |
| Description: | Percentage of participants who develop treatment-emergent anti-drug antibodies to domvanalimab |
Details
| Phase: | Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | Arcus Biosciences, Inc. |
Trial Keywords
- Non Small Cell Lung Cancer
- Lung Cancer
- NSCLC
Last Updated
June 21, 2021
