A Study of GDC-0919 and Atezolizumab Combination Treatment in Participants With Locally Advanced or Metastatic Solid Tumors
|
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT02471846 |
|
Recruitment Status :
Completed
First Posted : June 15, 2015
Last Update Posted : October 22, 2019
|
Sponsor:
Genentech, Inc.
Information provided by (Responsible Party):
Genentech, Inc.
- Study Details
- Tabular View
- No Results Posted
- Disclaimer
- How to Read a Study Record
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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Solid Tumor | Drug: Atezolizumab Drug: GDC-0919 | Phase 1 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 158 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| 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 |
| Actual Study Start Date : | July 28, 2015 |
| Actual Primary Completion Date : | October 2, 2019 |
| Actual Study Completion Date : | October 2, 2019 |
Resource links provided by the National Library of Medicine
Drug Information available for:
Atezolizumab
| Arm | Intervention/treatment |
|---|---|
|
Experimental: Anti-PD-1/PD-L1 Relapsed Cohort I
Approximately 20 participants whose most recent anti-cancer therapy consisted of single-agent programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) blockade and achieved best response of confirmed complete or partial response, or stable disease will receive GDC-0919, at the MTD or maximum administered dose (MAD) determined during the dose-escalation stage, in combination with atezolizumab. Treatment may continue until unacceptable toxicity or disease progression with an unfavorable risk-benefit ratio.
|
Drug: Atezolizumab
Participants will receive atezolizumab at a fixed dose of 1200 milligrams (mg) via intravenous (IV) infusion on Day 1 of each 21-day cycle with the exception of biopsy cohort A, where atezolizumab administration will start on Cycle 2 Day 1.
Other Names:
Drug: GDC-0919 Participants will receive GDC-0919 by mouth (PO) twice daily (BID), specifically every 12 hours. During the dose-escalation stage, the first cohort will receive GDC-0919 at a starting dose of 50 mg PO BID. Dosing will commence on Day -1 for Cycle 1 and follow subsequent 21-day (Days 1 to 21) dosing cycles. The dose will be modified based upon evaluation of DLTs, with single dose escalations not to exceed 2.5-fold of the previous dose. The proposed dosages for evaluation are 50, 100, 200, 400, 600, and 1000 mg PO BID. During the expansion stage, selected solid tumor types will be treated at the MTD or MAD as determined during the dose-escalation stage. |
|
Experimental: Anti-PD-1/PD-L1 Relapsed Cohort II
Approximately 20 participants whose most recent anti-cancer therapy consisted of single-agent PD-1/PD-L1 blockade and achieved unconfirmed partial response or stable disease will receive GDC-0919, at the MTD or MAD determined during the dose-escalation stage, in combination with atezolizumab. Treatment may continue until unacceptable toxicity or disease progression with an unfavorable risk-benefit ratio.
|
Drug: Atezolizumab
Participants will receive atezolizumab at a fixed dose of 1200 milligrams (mg) via intravenous (IV) infusion on Day 1 of each 21-day cycle with the exception of biopsy cohort A, where atezolizumab administration will start on Cycle 2 Day 1.
Other Names:
Drug: GDC-0919 Participants will receive GDC-0919 by mouth (PO) twice daily (BID), specifically every 12 hours. During the dose-escalation stage, the first cohort will receive GDC-0919 at a starting dose of 50 mg PO BID. Dosing will commence on Day -1 for Cycle 1 and follow subsequent 21-day (Days 1 to 21) dosing cycles. The dose will be modified based upon evaluation of DLTs, with single dose escalations not to exceed 2.5-fold of the previous dose. The proposed dosages for evaluation are 50, 100, 200, 400, 600, and 1000 mg PO BID. During the expansion stage, selected solid tumor types will be treated at the MTD or MAD as determined during the dose-escalation stage. |
|
Experimental: Biopsy Cohort A
Approximately 20 participants with melanoma, HNSCC, gastric, ovarian, Merkel cell, cervical, or endometrial cancer will receive GDC-0919 during Cycle 1, followed by combination treatment with GDC-0919 and atezolizumab from Cycle 2 onwards. Serial biopsies of extrahepatic lesions will be performed. Treatment may continue until unacceptable toxicity or disease progression with an unfavorable risk-benefit ratio.
|
Drug: Atezolizumab
Participants will receive atezolizumab at a fixed dose of 1200 milligrams (mg) via intravenous (IV) infusion on Day 1 of each 21-day cycle with the exception of biopsy cohort A, where atezolizumab administration will start on Cycle 2 Day 1.
Other Names:
Drug: GDC-0919 Participants will receive GDC-0919 by mouth (PO) twice daily (BID), specifically every 12 hours. During the dose-escalation stage, the first cohort will receive GDC-0919 at a starting dose of 50 mg PO BID. Dosing will commence on Day -1 for Cycle 1 and follow subsequent 21-day (Days 1 to 21) dosing cycles. The dose will be modified based upon evaluation of DLTs, with single dose escalations not to exceed 2.5-fold of the previous dose. The proposed dosages for evaluation are 50, 100, 200, 400, 600, and 1000 mg PO BID. During the expansion stage, selected solid tumor types will be treated at the MTD or MAD as determined during the dose-escalation stage. |
|
Experimental: Biopsy Cohort B
Approximately 20 participants with melanoma, HNSCC, gastric, ovarian, Merkel cell, cervical, or endometrial cancer will receive atezolizumab during Cycle 1, followed by combination treatment with GDC-0919 and atezolizumab from Cycle 2 onwards. Serial biopsies of extrahepatic lesions will be performed. Treatment may continue until unacceptable toxicity or disease progression with an unfavorable risk-benefit ratio.
|
Drug: Atezolizumab
Participants will receive atezolizumab at a fixed dose of 1200 milligrams (mg) via intravenous (IV) infusion on Day 1 of each 21-day cycle with the exception of biopsy cohort A, where atezolizumab administration will start on Cycle 2 Day 1.
Other Names:
Drug: GDC-0919 Participants will receive GDC-0919 by mouth (PO) twice daily (BID), specifically every 12 hours. During the dose-escalation stage, the first cohort will receive GDC-0919 at a starting dose of 50 mg PO BID. Dosing will commence on Day -1 for Cycle 1 and follow subsequent 21-day (Days 1 to 21) dosing cycles. The dose will be modified based upon evaluation of DLTs, with single dose escalations not to exceed 2.5-fold of the previous dose. The proposed dosages for evaluation are 50, 100, 200, 400, 600, and 1000 mg PO BID. During the expansion stage, selected solid tumor types will be treated at the MTD or MAD as determined during the dose-escalation stage. |
|
Experimental: Dose-Escalation Cohort(s)
Approximately 6 to 65 participants will be enrolled and treated at escalating doses of GDC-0919 in combination with fixed-dose atezolizumab. Treatment may continue until unacceptable toxicity or disease progression with an unfavorable risk-benefit ratio. Successive groups of at least 3 participants will be evaluated during a 21-day window for DLTs, which will determine the enrollment and dosing for subsequent cohorts in the dose-escalation stage. The MTD or MAD, whichever is reached first, will be considered for the expansion stage.
|
Drug: Atezolizumab
Participants will receive atezolizumab at a fixed dose of 1200 milligrams (mg) via intravenous (IV) infusion on Day 1 of each 21-day cycle with the exception of biopsy cohort A, where atezolizumab administration will start on Cycle 2 Day 1.
Other Names:
Drug: GDC-0919 Participants will receive GDC-0919 by mouth (PO) twice daily (BID), specifically every 12 hours. During the dose-escalation stage, the first cohort will receive GDC-0919 at a starting dose of 50 mg PO BID. Dosing will commence on Day -1 for Cycle 1 and follow subsequent 21-day (Days 1 to 21) dosing cycles. The dose will be modified based upon evaluation of DLTs, with single dose escalations not to exceed 2.5-fold of the previous dose. The proposed dosages for evaluation are 50, 100, 200, 400, 600, and 1000 mg PO BID. During the expansion stage, selected solid tumor types will be treated at the MTD or MAD as determined during the dose-escalation stage. |
|
Experimental: Expansion Cohorts
Approximately 160 participants (40 per diagnosis) with NSCLC, RCC, TNBC, and UBC will receive GDC-0919, at the MTD or MAD determined during the dose-escalation stage, in combination with Atezolizumab. Treatment may continue until unacceptable toxicity or disease progression with an unfavorable risk-benefit ratio.
|
Drug: Atezolizumab
Participants will receive atezolizumab at a fixed dose of 1200 milligrams (mg) via intravenous (IV) infusion on Day 1 of each 21-day cycle with the exception of biopsy cohort A, where atezolizumab administration will start on Cycle 2 Day 1.
Other Names:
Drug: GDC-0919 Participants will receive GDC-0919 by mouth (PO) twice daily (BID), specifically every 12 hours. During the dose-escalation stage, the first cohort will receive GDC-0919 at a starting dose of 50 mg PO BID. Dosing will commence on Day -1 for Cycle 1 and follow subsequent 21-day (Days 1 to 21) dosing cycles. The dose will be modified based upon evaluation of DLTs, with single dose escalations not to exceed 2.5-fold of the previous dose. The proposed dosages for evaluation are 50, 100, 200, 400, 600, and 1000 mg PO BID. During the expansion stage, selected solid tumor types will be treated at the MTD or MAD as determined during the dose-escalation stage. |
Primary Outcome Measures :
- Percentage of Participants With Dose-limiting Toxicities (DLTs) [ Time Frame: From Day -1 to 21 of Cycle 1 (each cycle is 21 days) ]
- Percentage of Participants With Adverse Events [ Time Frame: From Screening until new anti-cancer therapy or up to 60 days after last dose (up to approximately 3 years) ]
Secondary Outcome Measures :
- Maximum Tolerated Dose (MTD) of GDC-0919 [ Time Frame: From Day -1 to 21 of Cycle 1 (each cycle is 21 days) ]
- Recommended Phase II Dose (RP2D) for GDC-0919 [ Time Frame: From Day -1 to 21 of Cycle 1 (each cycle is 21 days) ]
- Number of Treatment Cycles Received With GDC-0919 and Atezolizumab [ Time Frame: From Day -1 of Cycle 1 (each cycle is 21 days) until treatment discontinuation (up to approximately 3 years) ]
- Dose Intensity of GDC-0919 and Atezolizumab [ Time Frame: From Day -1 of Cycle 1 (each cycle is 21 days) until treatment discontinuation (up to approximately 3 years) ]
- Percentage of Participants With Anti-therapeutic Antibody (ATA) Response to Atezolizumab [ Time Frame: 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) ]
- Plasma Maximum Concentration (Cmax) of GDC-0919 [ Time Frame: Post-dose on Day -1 of Cycle 1 (each cycle is 21 days) and Day 1 of Cycle 2 ]
- Plasma Minimum Concentration (Cmin) of GDC-0919 [ Time Frame: Pre-dose from Day -1 of Cycle 1 (each cycle is 21 days) through Day 1 of Cycle 8 ]
- Area Under the Concentration-time Curve to the Last Measurable Concentration (AUC0-last) of GDC-0919 [ Time Frame: Pre-dose and post-dose from Day -1 of Cycle 1 (each cycle is 21 days) through Day 1 of Cycle 8 ]
- Time to Maximum Concentration (Tmax) of GDC-0919 [ Time Frame: Post-dose on Day -1 of Cycle 1 (each cycle is 21 days) and Day 1 of Cycle 2 ]
- Serum Cmax of Atezolizumab [ Time Frame: 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) ]
- Serum Cmin of Atezolizumab [ Time Frame: Pre-dose from Day 1 of Cycle 1 up to 120 days after last dose of atezolizumab (up to approximately 3 years) ]
- 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 [ Time Frame: From Screening until disease progression, death, new anti-cancer therapy, or premature study withdrawal (up to approximately 3 years) ]
- Duration of Objective Response According to RECIST v1.1 as Determined by the Investigator [ Time Frame: From Screening until disease progression, death, new anti-cancer therapy, or premature study withdrawal (up to approximately 3 years) ]
- Percentage of Participants With Objective Response According to Modified RECIST as Determined by the Sponsor [ Time Frame: From Screening until disease progression, death, new anti-cancer therapy, or premature study withdrawal (up to approximately 3 years) ]
- Duration of Objective Response According to Modified RECIST as Determined by the Sponsor [ Time Frame: From Screening until disease progression, death, new anti-cancer therapy, or premature study withdrawal (up to approximately 3 years) ]
Information from the National Library of Medicine
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02471846
Locations
Show 18 study locations
Sponsors and Collaborators
Genentech, Inc.
Investigators
| Study Director: | Clinical Trials | Hoffmann-La Roche |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Genentech, Inc. |
| ClinicalTrials.gov Identifier: | NCT02471846 |
| Other Study ID Numbers: |
GO29779 2015-001741-88 ( EudraCT Number ) |
| First Posted: | June 15, 2015 Key Record Dates |
| Last Update Posted: | October 22, 2019 |
| Last Verified: | October 2019 |
Additional relevant MeSH terms:
|
Neoplasms Atezolizumab Immune Checkpoint Inhibitors |
Molecular Mechanisms of Pharmacological Action Antineoplastic Agents, Immunological Antineoplastic Agents |