Clinical trial NCT03846310: A Study to Evaluate Immunotherapy Combinations in Participants With Lung Cancer
Official title: A Phase 1/1b Study to Evaluate the Safety and Tolerability of Immunotherapy Combinations in Participants With Lung Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Non Small Cell Lung Cancer Metastatic
Non Small Cell Lung Cancer
Nonsquamous Nonsmall Cell Neoplasm of Lung
Sensitizing EGFR Gene Mutation
Lead sponsor: Arcus Biosciences, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Gilead Sciences
First posted: 2019-02-19
Enrollment: 77
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: 3+3 dose escalation
Primary purpose: TREATMENT

Brief 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).

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Percentage of participants with Adverse Events
timeFrame: From first study treatment administration until up to 90 days after the last dose (Approximately 1 year)
measure: Percentage of participants who experience a Dose Limiting Toxicity
timeFrame: From first study treatment administration through Day 21
Secondary outcomes:
measure: Percentage of participants with anti-drug antibodies to zimberelimab
timeFrame: 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).
measure: Plasma concentration of etrumadenant
timeFrame: 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).
measure: Serum concentration of zimberelimab
timeFrame: 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).
measure: Progression Free Survival (PFS)
timeFrame: 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)
measure: Duration of Response
timeFrame: 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)
measure: Percentage of Participants with Disease Control (complete response, partial response, or stable disease) for >6 months
timeFrame: From study enrollment until disease progression or loss of clinical benefit (up to approximately 3-5 years)
measure: Percentage of participants with Objective Response
timeFrame: 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)
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Arizona Cancer Research Center (ACRC)
state: Arizona
city: Fort Myers
country: United States
facility: SCRI Florida Cancer Specialists - South
state: Florida
city: Tavares
country: United States
facility: SCRI Florida Cancer Specialists - North
state: Florida
city: Nashville
country: United States
facility: SCRI Tennessee Oncology - Nashville
state: Tennessee
city: Dallas
country: United States
facility: USO Texas Oncology - Dallas (Baylor Charles A. Sammons Cancer Center)
state: Texas
city: Fairfax
country: United States
facility: USO Virginia Cancer Specialist
state: Virginia
city: Norfolk
country: United States
facility: USO Virginia Oncology Associates
state: Virginia
city: Spokane
country: United States
facility: Medical Oncology Associates/Summit Cancer Center
state: Washington
city: Suwon-si
country: Korea, Republic of
facility: The Catholic University of Korea St. Vincent Hospital
state: Gyeonggi
city: Cheongju-si
country: Korea, Republic of
facility: Chungbuk National University Hospital
city: Seongnam-si
country: Korea, Republic of
facility: Bundang CHA Medical Center
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Asan Medical Centre
city: Seoul
country: Korea, Republic of
facility: Seoul St. Mary's Hospital
city: Suwon
country: Korea, Republic of
facility: Seoul National University Hospital
city: Singapore
country: Singapore
facility: National University Hospital
city: Singapore
country: Singapore
facility: National Cancer Centre Singapore
city: Changhua
country: Taiwan
facility: Changhua Christian Hospital
city: New Taipei City
country: Taiwan
facility: Taipei Medical University - Shuang Ho Hospital
city: Tainan City
country: Taiwan
facility: Chi Mei Hospital, Liouying
city: Taipei City
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei City
country: Taiwan
facility: Tri Service General Hospital
Study officials:
affiliation: Arcus Biosciences, Inc.
name: Medical Director
role: STUDY_DIRECTOR
References: