Clinical trial NCT02471846: A Study of GDC-0919 and Atezolizumab Combination Treatment in Participants With Locally Advanced or Metastatic Solid Tumors
Official title: A Phase Ib, Open-Label, Dose-Escalation Study of the Safety and Pharmacology of GDC-0919 Administered With Atezolizumab in Patients With Locally Advanced or Metastatic Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Solid Tumor
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2015-06-15
Enrollment: 158
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will evaluate the safety, tolerability, and pharmacokinetics of the combination of GDC-0919 and atezolizumab in participants with locally advanced, recurrent, or metastatic incurable solid malignancy that has progressed after available standard therapy or for which standard therapy is ineffective, intolerable, or inappropriate. Participants will be enrolled in two stages, including a dose-escalation stage and an expansion stage.


Eligibility criteria: Inclusion Criteria:

* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Life expectancy at least 12 weeks
* Adequate hematologic and end organ function
* Negative pregnancy test and willingness to utilize contraception among women of childbearing potential
* Locally advanced, recurrent, or metastatic incurable solid malignancy with measurable disease per RECIST v1.1
* Progression following at least one standard therapy; or standard therapy considered ineffective, intolerable, or inappropriate; or use of an investigational agent recognized as a standard of care
* For the expansion stage, histologically confirmed renal cell cancer (RCC), urothelial bladder cancer (UBC), triple-negative breast cancer (TNBC), non-small cell lung cancer (NSCLC), melanoma, head and neck squamous cell carcinoma (HNSCC), gastric cancer, ovarian cancer, cervical cancer, endometrial cancer, or Merkel cell cancer
* For the expansion stage, evaluable for PD-L1 expression
* Anti PD-1/PD-L1 relapsed cohorts (I and II), participants whose most recent anti-cancer therapy consisted of single-agent PD-1/PD-L1 blockade will be enrolled

Exclusion Criteria:

* Significant cardiovascular or liver disease
* Major surgery within 28 days of study drug
* Any anti-cancer therapy within 3 weeks of study drug
* Malabsorption syndrome or poor upper gastrointestinal integrity
* Primary central nervous system (CNS) malignancy or active metastases within 5 years
* Uncontrolled tumor pain
* Autoimmune disease other than stable hypothyroidism or vitiligo
* Human immunodeficiency virus (HIV), active hepatitis B or C, or tuberculosis
* Signs/symptoms of infection, or use of antibiotics within 2 weeks of study drug
* Live attenuated vaccine within 4 weeks of study drug
* Known history or predisposition to QT interval prolongation
* Prior cancer immunotherapy, specifically indoleamine 2,3-dioxygenase (IDO) or tryptophan 2,3-dioxygenase (TDO) inhibitors, T-cell costimulatory receptor agonist antibodies, or checkpoint inhibitors among certain participants

Primary outcomes:
measure: Percentage of Participants With Dose-limiting Toxicities (DLTs)
timeFrame: From Day -1 to 21 of Cycle 1 (each cycle is 21 days)
measure: Percentage of Participants With Adverse Events
timeFrame: From Screening until new anti-cancer therapy or up to 60 days after last dose (up to approximately 3 years)
Secondary outcomes:
measure: Maximum Tolerated Dose (MTD) of GDC-0919
timeFrame: From Day -1 to 21 of Cycle 1 (each cycle is 21 days)
measure: Recommended Phase II Dose (RP2D) for GDC-0919
timeFrame: From Day -1 to 21 of Cycle 1 (each cycle is 21 days)
measure: Number of Treatment Cycles Received With GDC-0919 and Atezolizumab
timeFrame: From Day -1 of Cycle 1 (each cycle is 21 days) until treatment discontinuation (up to approximately 3 years)
measure: Dose Intensity of GDC-0919 and Atezolizumab
timeFrame: From Day -1 of Cycle 1 (each cycle is 21 days) until treatment discontinuation (up to approximately 3 years)
measure: Percentage of Participants With Anti-therapeutic Antibody (ATA) Response to Atezolizumab
timeFrame: Pre-dose from Day 1 of Cycle 1 (each cycle is 21 days) up to 120 days after last dose of atezolizumab (up to approximately 3 years)
measure: Plasma Maximum Concentration (Cmax) of GDC-0919
timeFrame: Post-dose on Day -1 of Cycle 1 (each cycle is 21 days) and Day 1 of Cycle 2
measure: Plasma Minimum Concentration (Cmin) of GDC-0919
timeFrame: Pre-dose from Day -1 of Cycle 1 (each cycle is 21 days) through Day 1 of Cycle 8
measure: Area Under the Concentration-time Curve to the Last Measurable Concentration (AUC0-last) of GDC-0919
timeFrame: Pre-dose and post-dose from Day -1 of Cycle 1 (each cycle is 21 days) through Day 1 of Cycle 8
measure: Time to Maximum Concentration (Tmax) of GDC-0919
timeFrame: Post-dose on Day -1 of Cycle 1 (each cycle is 21 days) and Day 1 of Cycle 2
measure: Serum Cmax of Atezolizumab
timeFrame: Post-dose from Day 1 of Cycle 1 (each cycle is 21 days) up to 120 days after last dose of atezolizumab (up to approximately 3 years)
measure: Serum Cmin of Atezolizumab
timeFrame: Pre-dose from Day 1 of Cycle 1 up to 120 days after last dose of atezolizumab (up to approximately 3 years)
measure: Percentage of Participants With Objective Response According to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) as Determined by the Investigator
timeFrame: From Screening until disease progression, death, new anti-cancer therapy, or premature study withdrawal (up to approximately 3 years)
measure: Duration of Objective Response According to RECIST v1.1 as Determined by the Investigator
timeFrame: From Screening until disease progression, death, new anti-cancer therapy, or premature study withdrawal (up to approximately 3 years)
measure: Percentage of Participants With Objective Response According to Modified RECIST as Determined by the Sponsor
timeFrame: From Screening until disease progression, death, new anti-cancer therapy, or premature study withdrawal (up to approximately 3 years)
measure: Duration of Objective Response According to Modified RECIST as Determined by the Sponsor
timeFrame: From Screening until disease progression, death, new anti-cancer therapy, or premature study withdrawal (up to approximately 3 years)
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: HonorHealth Research Institute - Bisgrove
state: Arizona
city: Santa Monica
country: United States
facility: The Angeles Clinic and Research Institute, Santa Monica Office
state: California
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
city: New Haven
country: United States
facility: Yale Cancer Center
state: Connecticut
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center and Research Inst.
state: Florida
city: Baltimore
country: United States
facility: Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
state: Maryland
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Marseille
country: France
facility: Hopital Nord AP-HM
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center - Oncology
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital Universitario HM Sanchinarro-CIOCC
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Jung KH, LoRusso P, Burris H, Gordon M, Bang YJ, Hellmann MD, Cervantes A, Ochoa de Olza M, Marabelle A, Hodi FS, Ahn MJ, Emens LA, Barlesi F, Hamid O, Calvo E, McDermott D, Soliman H, Rhee I, Lin R, Pourmohamad T, Suchomel J, Tsuhako A, Morrissey K, Mahrus S, Morley R, Pirzkall A, Davis SL. Phase I Study of the Indoleamine 2,3-Dioxygenase 1 (IDO1) Inhibitor Navoximod (GDC-0919) Administered with PD-L1 Inhibitor (Atezolizumab) in Advanced Solid Tumors. Clin Cancer Res. 2019 Jun 1;25(11):3220-3228. doi: 10.1158/1078-0432.CCR-18-2740. Epub 2019 Feb 15.