Safety and Pharmacokinetics (PK) of Escalating Doses of Tiragolumab as a Single Agent and in Combination With Atezolizumab and/or Other Anti-Cancer Therapies in Locally Advanced or Metastatic Tumors
Study Details
Study Description
Brief Summary
This first-in-human open-label, multicenter, dose-escalation and expansion study is designed to evaluate the safety, tolerability, and PK of tiragolumab alone or in combination with atezolizumab and/or other anti-cancer therapies in participants with locally advanced, recurrent, or metastatic incurable tumors for whom standard therapy does not exist, has proven to be ineffective or intolerable, or is considered inappropriate, or for whom a clinical trial of an investigational agent is a recognized standard of care.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Phase Ia Dose-Escalation Stage: Tiragolumab Cohorts of at least 3 participants each will be treated with escalating doses of tiragolumab. |
Drug: Tiragolumab
Several dose levels will be evaluated for tiragolumab administered as a single agent and in combination with atezolizumab and/or other anti-cancer therapies. Tiragolumab will be given via IV infusion on Day 1 of each cycle (21-day or 28-day depending on study cohort and phase) until disease progression or loss of clinical benefit. Those who discontinue treatment with single-agent tiragolumab may receive combination treatment with tiragolumab and atezolizumab and/or other anti-cancer therapies. Combination treatment may continue until disease progression or loss of clinical benefit.
Other Names:
|
| Experimental: Phase Ia Dose-Expansion Stage: Tiragolumab Participants will be treated with tiragolumab at or below the maximum tolerated dose (MTD) or maximum administered dose (MAD) in the study. |
Drug: Tiragolumab
Several dose levels will be evaluated for tiragolumab administered as a single agent and in combination with atezolizumab and/or other anti-cancer therapies. Tiragolumab will be given via IV infusion on Day 1 of each cycle (21-day or 28-day depending on study cohort and phase) until disease progression or loss of clinical benefit. Those who discontinue treatment with single-agent tiragolumab may receive combination treatment with tiragolumab and atezolizumab and/or other anti-cancer therapies. Combination treatment may continue until disease progression or loss of clinical benefit.
Other Names:
|
| Experimental: Phase Ib Q3W Dose-Escalation Stage: Tiragolumab+Atezolizumab A minimum of 3 participants will be treated for each dose level of tiragolumab in combination with a fixed dose of atezolizumab with tiragolumab being administered prior to atezolizumab. |
Drug: Atezolizumab
Atezolizumab will be given as 1200 mg via IV infusion on Day 1 of each 21-day cycle or as 1680 mg via IV infusion on Day 1 of each 28-day cycle.
Other Names:
Drug: Tiragolumab
Several dose levels will be evaluated for tiragolumab administered as a single agent and in combination with atezolizumab and/or other anti-cancer therapies. Tiragolumab will be given via IV infusion on Day 1 of each cycle (21-day or 28-day depending on study cohort and phase) until disease progression or loss of clinical benefit. Those who discontinue treatment with single-agent tiragolumab may receive combination treatment with tiragolumab and atezolizumab and/or other anti-cancer therapies. Combination treatment may continue until disease progression or loss of clinical benefit.
Other Names:
|
| Experimental: Phase Ib Q3W Dose-Expansion Stage: Tiragolumab+Atezolizumab Participants will be treated every 3 weeks (Q3W) with tiragolumab at or below the MTD or MAD in combination with a fixed dose of atezolizumab with tiragolumab being administered prior to atezolizumab. |
Drug: Atezolizumab
Atezolizumab will be given as 1200 mg via IV infusion on Day 1 of each 21-day cycle or as 1680 mg via IV infusion on Day 1 of each 28-day cycle.
Other Names:
Drug: Tiragolumab
Several dose levels will be evaluated for tiragolumab administered as a single agent and in combination with atezolizumab and/or other anti-cancer therapies. Tiragolumab will be given via IV infusion on Day 1 of each cycle (21-day or 28-day depending on study cohort and phase) until disease progression or loss of clinical benefit. Those who discontinue treatment with single-agent tiragolumab may receive combination treatment with tiragolumab and atezolizumab and/or other anti-cancer therapies. Combination treatment may continue until disease progression or loss of clinical benefit.
Other Names:
|
| Experimental: Phase Ib Chemotherapy Dose-Expansion Stage: Cohort A In Cohort A, carboplatin or cisplatin and pemetrexed chemotherapy will be administered after atezolizumab and tiragolumab intravenous (IV) infusion. During induction phase, participants will receive atezolizumab and tiragolumab in combination with carboplatin or cisplatin and pemetrexed on Day 1 of each 21-day cycle for 4 to 6 cycles. During maintenance phase, participants will receive atezolizumab and tiragolumab in combination with pemetrexed on Day 1 of each 21-day cycle. |
Drug: Atezolizumab
Atezolizumab will be given as 1200 mg via IV infusion on Day 1 of each 21-day cycle or as 1680 mg via IV infusion on Day 1 of each 28-day cycle.
Other Names:
Drug: Tiragolumab
Several dose levels will be evaluated for tiragolumab administered as a single agent and in combination with atezolizumab and/or other anti-cancer therapies. Tiragolumab will be given via IV infusion on Day 1 of each cycle (21-day or 28-day depending on study cohort and phase) until disease progression or loss of clinical benefit. Those who discontinue treatment with single-agent tiragolumab may receive combination treatment with tiragolumab and atezolizumab and/or other anti-cancer therapies. Combination treatment may continue until disease progression or loss of clinical benefit.
Other Names:
Drug: Carboplatin
Carboplatin, AUC of 6 milligram per milliliter per minute (mg/ml/min) for Cohorts A and B and AUC of 5 mg/ml/min for Cohort C, IV infusion will be administered on Day 1 of each 21-day cycle after combination treatment of atezolizumab and tiragolumab IV infusion.
Drug: Cisplatin
Cisplatin 75 milligram per square meter (mg/m^2) IV infusion will be administered on day 1 of each 21-day cycle after combination treatment of atezolizumab and tiragolumab.
Drug: Pemetrexed
Pemetrexed 500 mg/m^2 IV infusion will be administered on Day 1 of each 21-day cycle after carboplatin or cisplatin IV infusion with combination treatment of atezolizumab and tiragolumab.
|
| Experimental: Phase Ib Chemotherapy Dose-Expansion Stage: Cohort B In Cohort B, carboplatin and paclitaxel chemotherapy will be administered after atezolizumab and tiragolumab IV infusion. During induction phase, participants will receive atezolizumab and tiragolumab in combination with carboplatin and paclitaxel on Day 1 of each 21-day cycle for 4 to 6 cycles. During maintenance phase, participants will receive atezolizumab and tiragolumab on Day 1 of each 21-day cycle (participants enrolled under protocol version 4) or Day 1 of each 28-day cycle (participants enrolled under protocol version 5). |
Drug: Atezolizumab
Atezolizumab will be given as 1200 mg via IV infusion on Day 1 of each 21-day cycle or as 1680 mg via IV infusion on Day 1 of each 28-day cycle.
Other Names:
Drug: Tiragolumab
Several dose levels will be evaluated for tiragolumab administered as a single agent and in combination with atezolizumab and/or other anti-cancer therapies. Tiragolumab will be given via IV infusion on Day 1 of each cycle (21-day or 28-day depending on study cohort and phase) until disease progression or loss of clinical benefit. Those who discontinue treatment with single-agent tiragolumab may receive combination treatment with tiragolumab and atezolizumab and/or other anti-cancer therapies. Combination treatment may continue until disease progression or loss of clinical benefit.
Other Names:
Drug: Carboplatin
Carboplatin, AUC of 6 milligram per milliliter per minute (mg/ml/min) for Cohorts A and B and AUC of 5 mg/ml/min for Cohort C, IV infusion will be administered on Day 1 of each 21-day cycle after combination treatment of atezolizumab and tiragolumab IV infusion.
Drug: Paclitaxel
Paclitaxel 200 mg/m^2 IV infusion will be administered on Day 1 of each 21-day cycle after combination treatment with atezolizumab and tiragolumab.
|
| Experimental: Phase Ib Chemotherapy Dose-Expansion Stage: Cohort C In Cohort C, carboplatin or cisplatin and etoposide chemotherapy will be administered after atezolizumab and tiragolumab IV infusion. During induction phase, participants will receive atezolizumab and tiragolumab in combination with carboplatin or cisplatin on Day 1 of each 21-day cycle and etoposide on Day 1 to 3 of each 21-day cycle for 4 cycles. During maintenance phase, participants will receive atezolizumab and tiragolumab on Day 1 of each 28-day cycle. |
Drug: Atezolizumab
Atezolizumab will be given as 1200 mg via IV infusion on Day 1 of each 21-day cycle or as 1680 mg via IV infusion on Day 1 of each 28-day cycle.
Other Names:
Drug: Tiragolumab
Several dose levels will be evaluated for tiragolumab administered as a single agent and in combination with atezolizumab and/or other anti-cancer therapies. Tiragolumab will be given via IV infusion on Day 1 of each cycle (21-day or 28-day depending on study cohort and phase) until disease progression or loss of clinical benefit. Those who discontinue treatment with single-agent tiragolumab may receive combination treatment with tiragolumab and atezolizumab and/or other anti-cancer therapies. Combination treatment may continue until disease progression or loss of clinical benefit.
Other Names:
Drug: Carboplatin
Carboplatin, AUC of 6 milligram per milliliter per minute (mg/ml/min) for Cohorts A and B and AUC of 5 mg/ml/min for Cohort C, IV infusion will be administered on Day 1 of each 21-day cycle after combination treatment of atezolizumab and tiragolumab IV infusion.
Drug: Cisplatin
Cisplatin 75 milligram per square meter (mg/m^2) IV infusion will be administered on day 1 of each 21-day cycle after combination treatment of atezolizumab and tiragolumab.
Drug: Etoposide
Etoposide 100 mg/m^2 IV infusion will be administered on Days 1, 2, and 3 of each 21-day cycle with combination treatment of atezolizumab and tiragolumab.
|
| Experimental: Phase Ib Chemotherapy Dose-Expansion Stage: Cohort D In Cohort D, participants will receive atezolizumab and tiragolumab on Day 1 and capecitabine on Day 1-14 of each 21-day cycle. |
Drug: Atezolizumab
Atezolizumab will be given as 1200 mg via IV infusion on Day 1 of each 21-day cycle or as 1680 mg via IV infusion on Day 1 of each 28-day cycle.
Other Names:
Drug: Tiragolumab
Several dose levels will be evaluated for tiragolumab administered as a single agent and in combination with atezolizumab and/or other anti-cancer therapies. Tiragolumab will be given via IV infusion on Day 1 of each cycle (21-day or 28-day depending on study cohort and phase) until disease progression or loss of clinical benefit. Those who discontinue treatment with single-agent tiragolumab may receive combination treatment with tiragolumab and atezolizumab and/or other anti-cancer therapies. Combination treatment may continue until disease progression or loss of clinical benefit.
Other Names:
Drug: Capecitabine
Capecitabine 1250 mg/m^2 oral dose will be administered twice daily (BID) on Days 1 through 14 of each 21-day cycle. On Day 1 of Cycle 1, the first dose of capecitabine will be administered prior to the atezolizumab and tiragolumab infusion.
|
| Experimental: Phase Ib Q4W Sequential Dose-Expansion Stage: Tiragolumab+Atezolizumab Participants will be treated every 4 weeks (Q4W) with fixed doses of tiragolumab and atezolizumab with tiragolumab being administered prior to atezolizumab. |
Drug: Atezolizumab
Atezolizumab will be given as 1200 mg via IV infusion on Day 1 of each 21-day cycle or as 1680 mg via IV infusion on Day 1 of each 28-day cycle.
Other Names:
Drug: Tiragolumab
Several dose levels will be evaluated for tiragolumab administered as a single agent and in combination with atezolizumab and/or other anti-cancer therapies. Tiragolumab will be given via IV infusion on Day 1 of each cycle (21-day or 28-day depending on study cohort and phase) until disease progression or loss of clinical benefit. Those who discontinue treatment with single-agent tiragolumab may receive combination treatment with tiragolumab and atezolizumab and/or other anti-cancer therapies. Combination treatment may continue until disease progression or loss of clinical benefit.
Other Names:
|
| Experimental: Phase Ib Q4W Coinfusion Expansion Cohort Tiragolumab+Atezolizumab Participants will be treated Q4W with fixed doses of tiragolumab and atezolizumab mixed and administered in one IV bag. |
Drug: Atezolizumab
Atezolizumab will be given as 1200 mg via IV infusion on Day 1 of each 21-day cycle or as 1680 mg via IV infusion on Day 1 of each 28-day cycle.
Other Names:
Drug: Tiragolumab
Several dose levels will be evaluated for tiragolumab administered as a single agent and in combination with atezolizumab and/or other anti-cancer therapies. Tiragolumab will be given via IV infusion on Day 1 of each cycle (21-day or 28-day depending on study cohort and phase) until disease progression or loss of clinical benefit. Those who discontinue treatment with single-agent tiragolumab may receive combination treatment with tiragolumab and atezolizumab and/or other anti-cancer therapies. Combination treatment may continue until disease progression or loss of clinical benefit.
Other Names:
|
| Experimental: Phase Ib Non-Chemotherapy Dose-Expansion Stage: Cohort NC1 In Cohort NC1, participants will receive atezolizumab and tiragolumab in combination with bevacizumab on Day 1 of each 21-day cycle. |
Drug: Atezolizumab
Atezolizumab will be given as 1200 mg via IV infusion on Day 1 of each 21-day cycle or as 1680 mg via IV infusion on Day 1 of each 28-day cycle.
Other Names:
Drug: Tiragolumab
Several dose levels will be evaluated for tiragolumab administered as a single agent and in combination with atezolizumab and/or other anti-cancer therapies. Tiragolumab will be given via IV infusion on Day 1 of each cycle (21-day or 28-day depending on study cohort and phase) until disease progression or loss of clinical benefit. Those who discontinue treatment with single-agent tiragolumab may receive combination treatment with tiragolumab and atezolizumab and/or other anti-cancer therapies. Combination treatment may continue until disease progression or loss of clinical benefit.
Other Names:
Drug: Bevacizumab
Bevacizumab 15 mg/kg IV infusion will be administered on Day 1 of each 21-day cycle after combination treatment of atezolizumab and tiragolumab.
|
| Experimental: Phase Ib Non-Chemotherapy Dose-Expansion Stage: Cohort NC2 In Cohort NC2, participants will receive tiragolumab in combination with pembrolizumab on Day 1 of each 21-day cycle. |
Drug: Tiragolumab
Several dose levels will be evaluated for tiragolumab administered as a single agent and in combination with atezolizumab and/or other anti-cancer therapies. Tiragolumab will be given via IV infusion on Day 1 of each cycle (21-day or 28-day depending on study cohort and phase) until disease progression or loss of clinical benefit. Those who discontinue treatment with single-agent tiragolumab may receive combination treatment with tiragolumab and atezolizumab and/or other anti-cancer therapies. Combination treatment may continue until disease progression or loss of clinical benefit.
Other Names:
Drug: Pembrolizumab
Pembrolizumab 200 mg IV infusion will be administered on Day 1 of each 21-day cycle after treatment with tiragolumab.
|
Outcome Measures
Primary Outcome Measures
- Percentage of Participants with Dose-Limiting Toxicities (DLTs) [From Baseline to the end of Cycle 1 (up to 21 days)]
- Percentage of Participants with Adverse Events (AEs) Graded per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0 [From Baseline up to 90 days after last dose of study treatment or until initiation of another systemic anti-cancer therapy (up to approximately 8 years)]
- Number of Cycles with Tiragolumab [From Baseline to last dose (up to approximately 8 years)]
- Phase Ia and Ib: Percentage of Participants with Anti-Drug Antibodies (ADAs) to Tiragolumab [Day 1 up to 8 years]
Phase (Ph) 1a: Pre-dose on Day 1, Cycles 1-4, 8, 16, every eight cycles (Q8C), at discontinuation (DC), every 30 days up to 120 days (cycle length 21 days); Phase 1b without Chemotherapy: Pre-dose on Day 1, Cycles 1-4, 8, then Q8C, DC (cycle length 21 days); Phase 1b (Chemotherapy Cohorts and Q4W): Pre-dose on Day 1, Cycles 1-4, 8, 12 and 16, then DC (cycle length 21/28 days).
- Phase Ib: Percentage of Participants with ADAs to Atezolizumab [Day 1 up to 8 years]
Phase 1b (without Chemotherapy): Pre-dose on Day 1, Cycles 1-4, 8, then Q8C, at DC, every 30 days up to 120 days (cycle length 21 days); Phase 1b (Chemotherapy Cohorts and Q4W): Pre-dose on Day 1, Cycles 1-4, 8, 12 and 16, then DC (cycle length 21/28 days).
Secondary Outcome Measures
- Area Under the Concentration-Time Curve (AUC) of Tiragolumab [Day 1 up to 8 years]
During Phase Ia and Phase Ib dose-escalation stages time frame is as follows: Pre-dose Day 1, Cycles 1-4, 8 (cycle length 21 days); Cycle 1: Post-dose-0.5 hour, 24 hours, Days 8 and 15; Day 1, Cycles 2-7 (Ph 1a), Cycles 2, 3, 4 ,8, 16 -0.5 hour post-dose; Ph1a and 1b - Q8C, DC; every 30 days up to 120 days. During Phase Ia dose-expansion stage and Phase Ib dose-expansion stages with and without chemotherapy time frame is as follows: Pre-dose Day 1,Cycles 1-4, 8 (cycle length 21/28 days); Cycle 1: Post-dose-0.5 hour, Days 2, 8 and 15 (D2, D8 and D15 only applicable to Q4W co-infusion cohort); Day 1, Cycles 2, 3, 4, 8, 12* 16 (C12* only applicable to Q4W and Chemotherapy cohorts): 0.5 hour post-dose; ph1a and 1b (Q3W)- Q8C, DC; every 30 days up to 120 days.
- Maximum Serum Concentration (Cmax) of Tiragolumab [Day 1 up to 8 years]
During Phase Ia and Phase Ib dose-escalation stages time frame is as follows: Pre-dose Day 1,Cycles 1-4, 8 (cycle length 21 days); Cycle 1: Post-dose-0.5 hour, 24 hours, Days 8 and 15; Day 1, Cycles 2-7 (Ph 1a), Cycles 2, 3, 4 ,8, 16 -0.5 h post-dose; ph1a and 1b - Q8C, DC; every 30 days up to 120 days. During Phase Ia dose-expansion stage and Phase Ib dose-expansion stages with and without chemotherapy time frame is as follows: Pre-dose Day 1,Cycles 1-4, 8 (cycle length 21/28 days); Cycle 1: Post-dose-0.5 hour, Days 2, 8 and 15 (D2, D8 and D15 only applicable to Q4W co-infusion cohort); Day 1, Cycles 2, 3, 4, 8, 12* 16 (C12* only applicable to Q4W and Chemotherapy cohorts): 0.5 hour post-dose; ph1a and 1b (Q3W)- Q8C, DC; every 30 days up to 120 days.
- Minimum Serum Concentration (Cmin) of Tiragolumab [Day 1 up to 8 years]
During Phase Ia and Phase Ib dose-escalation stages time frame is as follows: Pre-dose Day 1,Cycles 1-4, 8 (cycle length 21 days); Cycle 1: Post-dose-0.5 hour, 24 hours, Days 8 and 15; Day 1, Cycles 2-7 (Ph 1a), Cycles 2, 3, 4 ,8, 16 -0.5 hour post-dose; ph1a and 1b - Q8C, DC; every 30 days up to 120 days. During Phase Ia dose-expansion stage and Phase Ib dose-expansion stages with and without chemotherapy time frame is as follows: Pre-dose Day 1,Cycles 1-4, 8 (cycle length 21/28 days); Cycle 1: Post-dose-0.5 hour, Days 2, 8 and 15 (D2, D8 and D15 only applicable to Q4W co-infusion cohort); Day 1, Cycles 2, 3, 4, 8, 12* 16 (C12* only applicable to Q4W and Chemotherapy cohorts): 0.5 h post-dose; ph1a and 1b (Q3W)- Q8C, DC; every 30 days up to 120 days.
- Clearance (CL) of Tiragolumab [Day 1 up to 8 years]
During Phase Ia and Phase Ib dose-escalation stages time frame is as follows: Pre-dose Day 1,Cycles 1-4, 8 (cycle length 21 days); Cycle 1: Post-dose-0.5 hour, 24 hours, Days 8 and 15; Day 1, Cycles 2-7 (Ph 1a), Cycles 2, 3, 4 ,8, 16 -0.5 hour post-dose; ph1a and 1b - Q8C, DC; every 30 days up to 120 days. During Phase Ia dose-expansion stage and Phase Ib dose-expansion stages with and without chemotherapy time frame is as follows: Pre-dose Day 1,Cycles 1-4, 8 (cycle length 21/28 days); Cycle 1: Post-dose-0.5 hour, Days 2, 8 and 15 (D2, D8 and D15 only applicable to Q4W co-infusion cohort); Day 1, Cycles 2, 3, 4, 8, 12* 16 (C12* only applicable to Q4W and Chemotherapy cohorts): 0.5 hour post-dose; ph1a and 1b (Q3W)- Q8C, DC; every 30 days up to 120 days.
- Volume of Distribution at Steady State (Vss) of Tiragolumab [Day 1 up to 8 years]
During Phase Ia and Phase Ib dose-escalation stages time frame is as follows: Pre-dose Day 1,Cycles 1-4, 8 (cycle length 21 days); Cycle 1: Post-dose-0.5 hour, 24 hours, Days 8 and 15; Day 1, Cycles 2-7 (Ph 1a), Cycles 2, 3, 4 ,8, 16 -0.5 hour post-dose; ph1a and 1b - Q8C, DC; every 30 days up to 120 days. During Phase Ia dose-expansion stage and Phase Ib dose-expansion stages with and without chemotherapy time frame is as follows: Pre-dose Day 1, Cycles 1-4, 8 (cycle length 21/28 days); Cycle 1: Post-dose-0.5 hour, Days 2, 8 and 15 (D2, D8 and D15 only applicable to Q4W co-infusion cohort); Day 1, Cycles 2, 3, 4, 8, 12* 16 (C12* only applicable to Q4W and Chemotherapy cohorts): 0.5 hour post-dose; ph1a and 1b (Q3W)- Q8C, DC; every 30 days up to 120 days.
- Cmax of Atezolizumab [Day 1 up to 8 years]
During Phase Ib dose-escalation stage time frame will be as follows: Pre-dose Day 1,Cycles 1-4, 8 (cycle length 21 days); Cycle 1: Post-dose-0.5 hour, 24 hours, Days 8 and 15; Day 1, Cycles 2 ,3, 4, 8, 16: 0.5 hour post-dose; Q8C, DC; every 30 days up to 120 days. During Phase Ib dose-expansion stages time frame will be as follows: Pre-dose on Day 1 of Cycles (cycle length 21/28 days) 1-4, 8, 12*, 16 (C12* only applicable to Q4W and Chemotherapy cohorts); Post-dose 0.5 hour on Day 1 of Cycles 1-4, 8, 12, 16; then Q8C until/at DC, every 30 days up to 120 days. For Q4W co-infusion cohort only: post-dose Days 2, 8 and 15 of Cycle 1.
- Cmin of Atezolizumab [Day 1 up to 8 years]
During Phase Ib dose-escalation stage time frame will be as follows: Pre-dose Day 1, Cycles 1-4, 8 (cycle length 21 days); Cycle 1: Post-dose-0.5 hour, 24 hours, Days 8 and 15; Day 1, Cycles 2 ,3, 4, 8, 16: 0.5 hour post-dose; Q8C, DC; every 30 days up to 120 days. During Phase Ib dose-expansion stages time frame will be as follows: Pre-dose on Day 1 of Cycles (cycle length 21/28 days) 1-4,8, 12*, 16 (C12* only applicable to Q4W and Chemotherapy cohorts); Post-dose 0.5 hour on Day 1 of Cycles 1-4, 8, 12, 16; then Q8C until/at DC, every 30 days up to 120 days. For Q4W co-infusion cohort only: post-dose Days 2, 8 and 15 of Cycle 1.
- Plasma Concentration of Cisplatin [Pre-dose (5 min) and post-dose (1 hour) on Day 1 of Cycles 1 and 3 (cycle length 21 days)]
- Plasma Concentration of Carboplatin [Pre-dose (5 min) and post-dose (1 hour) on Day 1 of Cycles 1 and 3 (cycle length 21 days)]
- Plasma Concentration of Pemetrexed [Pre-dose (5 min) and post-dose (1 hour) on Day 1 of Cycles 1 and 3 (cycle length 21 days)]
- Plasma Concentration of Paclitaxel [Pre-dose (5 min) and post-dose (1 hour) on Day 1 of Cycles 1 and 3 (cycle length 21 days)]
- Plasma Concentration of Etoposide [Pre-dose (5 min) and post-dose (1 hour) on Day 1 of Cycles 1 and 3 (cycle length 21 days)]
- Plasma Concentration of Capecitabine [Pre-dose (5 min) on Day 1 of Cycle 1 and post-dose (2 hours) on Day 1 of Cycle 3 (cycle length 21 days)]
- Objective Response According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 [From Baseline until disease progression (up to 8 years)]
- Duration of Objective Response (DOR) According to RECIST Version 1.1 [From Baseline until disease progression (up to 8 years)]
- Progression-Free Survival (PFS) According to RECIST Version 1.1 [From Baseline until disease progression (up to 8 years)]
- Overall survival (OS) According to RECIST Version 1.1 [Baseline until death from any cause (up to approximately 8 years)]
Eligibility Criteria
Criteria
Inclusion Criteria:
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Adults 18 years of age or older
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Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
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Life expectancy at least 12 weeks
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Adequate hematologic and end organ function
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Histologic documentation of locally advanced, recurrent, or metastatic incurable malignancy that has progressed after at least one available standard therapy; or for which standard therapy has proven ineffective, intolerable, or considered inappropriate; or for which a clinical trial of an investigational agent is a recognized standard of care
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Confirmed availability of representative tumor specimens
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Measurable disease according to RECIST Version 1.1
Exclusion Criteria:
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Any anti-cancer therapy, whether investigational or approved, including chemotherapy, hormonal therapy, or radiotherapy, within 3 weeks prior to initiation of study treatment
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Malignancies other than disease under study within 5 years prior to Day 1 of Cycle 1
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Primary central nervous system (CNS) malignancy, or untreated/active CNS metastases
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Leptomeningeal disease
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History of idiopathic pulmonary fibrosis, pneumonitis, organizing pneumonia, or evidence of active pneumonitis on Screening chest computed tomograph (CT) scan
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History of autoimmune disease
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Positive human immunodeficiency virus (HIV) test
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Active hepatitis B or C, or tuberculosis
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Severe infection within 4 weeks prior to randomization
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Prior allogeneic bone marrow or solid organ transplant
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Significant cardiovascular disease
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Known clinically significant liver disease
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Honor Health Research Institute | Scottsdale | Arizona | United States | 85258 |
| 2 | University of California Los Angeles | Santa Monica | California | United States | 90404 |
| 3 | University of Colorado | Aurora | Colorado | United States | 80045-2517 |
| 4 | Yale Cancer Center | New Haven | Connecticut | United States | 06520 |
| 5 | Johns Hopkins Sidney Kimmel Comprehensive Cancer Center | Baltimore | Maryland | United States | 21287 |
| 6 | Beth Israel Deaconess Medical Center | Boston | Massachusetts | United States | 02215 |
| 7 | Dana Farber Cancer Institute | Boston | Massachusetts | United States | 02215 |
| 8 | Henry Ford Hospital | Detroit | Michigan | United States | 48202 |
| 9 | Columbia University Medical Center | New York | New York | United States | 10032 |
| 10 | Memorial Sloan-Kettering Cancer Center | New York | New York | United States | 10065 |
| 11 | Uni of Pittsburgh Cancer Inst. ; Oncology | Pittsburgh | Pennsylvania | United States | 15232 |
| 12 | Rhode Island Hospital; Pharmacy Department | Providence | Rhode Island | United States | 02903 |
| 13 | Tennessee Onc., PLLC - SCRI | Nashville | Tennessee | United States | 37203 |
| 14 | Kinghorn Cancer Centre; St Vincents Hospital | Darlinghurst | New South Wales | Australia | 2010 |
| 15 | Peter MacCallum Cancer Center | North Melbourne | Victoria | Australia | 3051 |
| 16 | Princess Margaret Hospital | Toronto | Ontario | Canada | M4X 1K9 |
| 17 | Institut Bergonie CLCC Bordeaux | Bordeaux | France | 33000 | |
| 18 | Centre Léon Bérard Centre Régional de Lutte Contre Le Cancer Rhône Alpes | Lyon | France | 69008 | |
| 19 | Institut Curie | Paris | France | 75005 | |
| 20 | Institut Claudius Regaud; Departement Oncologie Medicale | Toulouse | France | 31059 | |
| 21 | Institut Gustave Roussy | Villejuif | France | 94805 | |
| 22 | National Cancer Center Hospital | Tokyo | Japan | 104-0045 | |
| 23 | The Cancer Institute Hospital of Japanese Foundation For Cancer Research | Tokyo | Japan | 135-8550 | |
| 24 | Seoul National University Hospital | Seoul | Korea, Republic of | 03080 | |
| 25 | Severance Hospital, Yonsei University Health System | Seoul | Korea, Republic of | 03722 | |
| 26 | Asan Medical Center | Seoul | Korea, Republic of | 05505 | |
| 27 | Samsung Medical Center | Seoul | Korea, Republic of | 06351 | |
| 28 | ICO L'Hospitalet; Servicio de oncologia medica | L Hospitalet De Llobregat | Barcelona | Spain | 08908 |
| 29 | Clinica Universitaria de Navarra; Servicio de oncología | Pamplona | Navarra | Spain | 31008 |
| 30 | Hospital del Mar | Barcelona | Spain | 08003 | |
| 31 | Hospital Univ Vall d'Hebron; Servicio de Oncologia | Barcelona | Spain | 08035 | |
| 32 | Hospital Universitario HM Sanchinarro-CIOCC; Oncología Médica | Madrid | Spain | 28050 | |
| 33 | Hospital Clinico Universitario de Valencia | Valencia | Spain | 46010 |
Sponsors and Collaborators
- Genentech, Inc.
Investigators
- Study Director: Clinical Trials, Hoffmann-La Roche
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- GO30103
- 2016-000944-33