A Study to Evaluate Immunotherapy Combinations in Participants With Lung Cancer

Non Small Cell Lung Cancer Clinical Trial

— ARC-4  

Official title:

A Phase 1/1b Study to Evaluate the Safety and Tolerability of Immunotherapy Combinations in Participants With Lung Cancer

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03846310
• Other study ID #: ARC-4 (AB928CSP0004)
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: April 1, 2019
• Est. completion date: August 2024

Study information

• Verified date: May 2024
• Source: Arcus Biosciences, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a Phase 1/1b, multicenter, open-label, dose-escalation and dose-expansion study to evaluate the safety, tolerability, pharmacokinetic (PK), pharmacodynamic, and clinical activity of etrumadenant (AB928) in combination with carboplatin and pemetrexed, with or without an anti-PD-1 antibody (pembrolizumab or zimberelimab), in participants with non-squamous Non-Small Cell Lung Cancer (NSCLC).

Description:

In the dose-escalation phase, escalating doses of etrumadenant in combination with carboplatin and pemetrexed at standard doses (Arm A), and etrumadenant in combination with carboplatin, pemetrexed and pembrolizumab (Arm B), may be assessed in participants with advanced NSCLC. Eligible participants will receive oral administration of etrumadenant as well as IV infused carboplatin, pemetrexed, with or without pembrolizumab in this phase. The recommended dose for expansion (RDE) of etrumadenant will be determined upon completion of the dose-escalation phase. In the dose-expansion phase, zimberelimab in combination with carboplatin and pemetrexed (Arm 1), and etrumadenant at RDE in combination with carboplatin, pemetrexed, and zimberelimab (Arm 2) may be assessed in eligible NSCLC participants who harbor an EGFR mutation and have progressed on EGFR Tyrosine Kinase Inhibitor (TKI) treatment(s). Overall duration of treatment will depend on how well the treatment is tolerated. Treatment may continue until unacceptable toxicity or progressive disease or other reasons specified in the protocol.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 77
• Est. completion date: August 2024
• Est. primary completion date: August 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Male or female participants; age = 18 years
• Pathologically confirmed nonsquamous NSCLC that is metastatic, locally advanced, or recurrent with progression
• Arm A participants must fulfill one of the following:
• Participant has a genetic alteration (mutation or rearrangement) and has received all available targeted therapy. Previous treatment with chemotherapy or PD-1/-L1 therapy is not allowed.
• Participant has not received any therapy for the disease under study and standard therapy is refused.
• Participant has progressed on PD-1/-L1 therapy (monotherapy or combination regimen). Previous treatment with chemotherapy is not allowed.
• Participant has progressed on PD-1/-L1 therapy (monotherapy or combination regimen) and has received less than 4 cycles of carboplatin/pemetrexed and further chemotherapy is appropriate.
• Participant has received any number of prior treatments and is without alternative or curative therapy.
• Arm B participants must fulfill one of the following:
• Participant has a genetic alteration (mutation or rearrangement) and has received all available targeted therapy. Previous treatment with chemotherapy or PD-1/-L1 therapy is not allowed.
• Participant has not received any therapy for the disease under study and standard therapy is refused.
• Participant has received any number of prior treatments and is without alternative or curative therapy.
• Arm 1 and Arm 2 participants must have a sensitizing epidermal growth factor receptor (EGFR) mutation with disease progression or treatment intolerance after one or more approved TKIs. Previous treatment with chemotherapy or PD-1/L-1 therapy is not allowed.
• No TKI therapy within 5 days of Cycle 1 Day 1
• The last dose of previous investigational therapy is at least 4 weeks or 5 half-lives prior to Cycle 1 Day 1.
• Must have at least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST v1.1)
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
• Confirm that an archival tissue sample is available and = 24 months old; if not, a new biopsy of a tumor lesion should be obtained at screening
• Adequate organ and marrow function

Exclusion Criteria:

• Use of any live vaccines against infectious diseases within 4 weeks (28 days) of initiation of investigational product
• Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the pre-screening or screening visit through 30 days after the last dose of etrumadenant, 90 days after the last dose of zimberelimab or pembrolizumab, or 6 months after the last dose of pemetrexed, whichever is longer
• 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
• Prior use of an adenosine pathway targeting agent
• Due to potential for drug-drug interactions with etrumadenant, participants must not

have had:

• Treatment with breast cancer resistance protein substrates or P-glycoprotein with a narrow therapeutic window, administered orally within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to initiation of study treatment.
• Treatment with known strong cytochrome P450 3A4 (CYP3A4) inducers and strong CYP3A4 inhibitors within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to initiation of study treatment

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non Small Cell Lung Cancer
• Non Small Cell Lung Cancer Metastatic
• Nonsquamous Nonsmall Cell Neoplasm of Lung
• Sensitizing EGFR Gene Mutation

Intervention

Drug:
• Etrumadenant
Etrumadenant is an A2aR and A2bR antagonist
• Zimberelimab
Zimberelimab is a fully human anti-PD-1 monoclonal antibody
• Carboplatin
Carboplatin administered as part of standard chemotherapy regimen
• Pemetrexed
Pemetrexed administered as part of standard chemotherapy regimen
• Pembrolizumab
Pembrolizumab is a humanized anti-PD-1 monoclonal antibody

Locations

Country	Name	City	State
Korea, Republic of	Chungbuk National University Hospital	Cheongju-si
Korea, Republic of	CHA Bundang Medical Center, CHA University	Seongnam-si
Korea, Republic of	Asan Medical Centre	Seoul
Korea, Republic of	Seoul St. Mary's Hospital, The Catholic University of Korea	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
Korea, Republic of	Seoul National University Hospital	Suwon
Korea, Republic of	St Vincent Hospital of the Catholic University of Korea	Suwon-si	Gyeonggi-do
Singapore	National Cancer Centre Singapore	Singapore
Singapore	National University Hospital	Singapore
Taiwan	Changhua Christian Hospital	Changhua
Taiwan	Taipei Medical University - Shuang Ho Hospital	New Taipei City
Taiwan	Chi Mei Hospital, Liouying	Tainan City
Taiwan	Tri-Service General Hospital	Taipei
Taiwan	National Taiwan University Hospital	Taipei City
United States	Texas Oncology - Baylor Charles A. Sammons Cancer Center	Dallas	Texas
United States	Virginia Cancer Specialists	Fairfax	Virginia
United States	Florida Cancer Specialists - South	Fort Myers	Florida
United States	Tennessee Oncology	Nashville	Tennessee
United States	Virginia Oncology Associates	Norfolk	Virginia
United States	USO Texas Oncology - San Antonio Medical Center	San Antonio	Texas
United States	Medical Oncology Associates, PS (dba Summit Cancer Centers)	Spokane	Washington
United States	Florida Cancer Specialists & Research Institute	Tavares	Florida
United States	Arizona Clinical Research Center	Tucson	Arizona

Sponsors (2)

Lead Sponsor	Collaborator
Arcus Biosciences, Inc.	Gilead Sciences

Countries where clinical trial is conducted

United States,  Korea, Republic of,  Singapore,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of participants with Adverse Events		From first study treatment administration until up to 90 days after the last dose (Approximately 1 year)
Primary	Percentage of participants who experience a Dose Limiting Toxicity		From first study treatment administration through Day 21
Secondary	Percentage of participants with anti-drug antibodies to zimberelimab		Recorded at baseline (screening), during the first 4 cycles of treatment (4 months) and 30 days post last dose (i.e. in total approximately 5 months).
Secondary	Plasma concentration of etrumadenant		Recorded at baseline (screening), during the first 4 cycles of treatment (4 months) and 30 days post last dose (i.e. in total approximately 5 months).
Secondary	Serum concentration of zimberelimab		Recorded at baseline (screening), during the first 4 cycles of treatment (4 months) and 30 days post last dose (i.e. in total approximately 5 months).
Secondary	Progression Free Survival (PFS)		From start of treatment up to the first occurrence of progressive disease or death from any cause, whichever occurs first (up to approximately 3-5 years)
Secondary	Duration of Response		From the date of first occurrence 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)
Secondary	Percentage of Participants with Disease Control (complete response, partial response, or stable disease) for >6 months		From study enrollment until disease progression or loss of clinical benefit (up to approximately 3-5 years)
Secondary	Percentage of participants with Objective Response		From study enrollment until participant discontinuation, first occurrence of progressive disease, or death from any cause, whichever occurs first (up to approximately 3-5 years)