Study of Atezolizumab in Combination With Cobimetinib in Participants With Locally Advanced or Metastatic Solid Tumors

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• Neoplasms 9,365

Neoplasms

9,365 studies on the registry are indexed under Neoplasms; 2,489 are open to participants now.

This study's enrollment of 153 is above the median of 50 across 7,253 interventional studies indexed under Neoplasms.

Lead sponsor

Hoffmann-La Roche is the lead sponsor of 2,061 studies on the registry; 85 are open to participants now.

Of its 319 completed or terminated interventional studies of FDA-regulated products, 239 (75%) have results posted.

Eligibility criteria

Study arms

• Experimental
  Dose-Escalation: Cobimetinib, Atezolizumab

  Participants will receive single dose of 800 milligrams (mg) of atezolizumab IV infusion on Day 1, 15 and 29 of Cycle 1 (cycle length=42 days \[14-day run-in period + 28-day concomitant dosing period\]), thereafter with atezolizumab IV dosing every 2 weeks (q2w) in all subsequent treatment cycles (28 days each). Combination with cobimetinib will begin on Cycle 1 Day 15 and will be given at increasing dose levels during Stage 1. During Stage 1, cobimetinib will be administered once daily (QD) orally for 21 consecutive days out of 28 days (21/7 dosing schedule) at a starting dose of 20 mg with escalation of 20 mg until the maximum tolerated dose (MTD; not more than 60 mg) for the two-drug combination.

  Drug: Atezolizumab · Drug: Cobimetinib

• Experimental
  Dose-Expansion: Cobimetinib, Atezolizumab

  Participants will receive single dose of 800 mg of atezolizumab IV infusion q2w in all subsequent treatment cycles (28 days each). Participants will receive cobimetinib at the selected recommended RP2D on Days 1-14 of each 28-day cycle during Stage 2.

  Drug: Atezolizumab · Drug: Cobimetinib

Interventions

• DrugAtezolizumab

  Atezolizumab will be administered at a fixed dose as specified via IV infusion.

  Also known as: MPDL3280

• DrugCobimetinib

  Cobimetinib will be administered orally at an escalating dose during Stage 1 and at RP2D during Stage 2.

  Also known as: GDC-0973

Primary outcomes

1. Phase I: Percentage of Participants With Dose-Limiting Toxicities (DLTs)

   Time frame: Day 15 to Day 42 of Cycle 1 (cycle length=42 days) of dose-escalation phase

2. Phase I: Maximum Tolerated Dose of Cobimetinib

   Time frame: Day 15 to Day 42 of Cycle 1 (cycle length=42 days) of dose-escalation phase

3. Phase I: Recommended Phase II Dose of Cobimetinib when Combined with Atezolizumab

   Time frame: Day 15 to Day 42 of Cycle 1 (cycle length=42 days) of dose-escalation phase

Secondary outcomes

1. Percentage of Participants With Anti-Therapeutic Antibody (ATA) Response to Azetolizumab

   Time frame: Pre-infusion (Hour 0) on Day 1 of Cycles 1, 2, 3, 4, 8 (cycle length=42 days for Cycle 1; 28 days for subsequent cycles) and at treatment completion visit (up to approximately 3.5 years)

2. Percentage of Participants With Adverse Events (AEs) or Serious AEs (SAEs)

   Time frame: Baseline up to approximately 3.5 years

3. Serum Maximum Concentration (Cmax) of Atezolizumab

   Time frame: Pre-infusion (Hour 0) on Day 1 of Cycles 2, 3, 4, 8 (cycle length=28 days) and at treatment completion visit (up to approximately 3.5 years); 30 minutes post-infusion (duration=60 minutes) on Cycle 1 Day 1 (cycle length=42 days)

4. Serum Minimum Concentration (Cmin) of Atezolizumab

   Time frame: Pre-infusion (Hour 0) on Day 1 of Cycles 2, 3, 4, 8 (cycle length=28 days) and at treatment completion visit (up to approximately 3.5 years)

5. Plasma Cmax of Cobimetinib

   Time frame: Pre-dose (Hour 0) and Hours 2, 4, 6 post-dose on Day 29 of Cycle 1 (cycle length=42 days) and Day 15 of Cycle 2 (cycle length=28 days)

6. Plasma Cmin of Cobimetinib

   Time frame: Pre-dose (Hour 0) on Day 29 of Cycle 1 (cycle length=42 days) and Day 15 of Cycle 2 (cycle length=28 days)

7. Area Under the Concentration-Time Curve (AUC) of Cobimetinib

   Time frame: Pre-dose (Hour 0) and Hours 2, 4, 6 post-dose on Day 29 of Cycle 1 (cycle length=42 days) and Day 15 of Cycle 2 (cycle length=28 days)

8. Percentage of Participants With Best Overall Response, as Determined by Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1

   Baseline up to 3.5 years (assessed at Baseline then every 8 weeks for the first 48 weeks following Day 1 of Cycle 1 \[cycle length=42 days\]; thereafter every 12 weeks until progressive disease \[PD\] or death due to any cause, whichever occurs first \[up to approximately 3.5 years\])

   Time frame: Baseline up to 3.5 years (detailed time frame is provided in the description)

9. Percentage of Participants With Objective Response (OR; Confirmed Complete Response or Partial Response) as Assessed by Investigator Using RECIST v1.1

   Time frame: Baseline up to 3.5 years (assessed at Baseline then every 8 weeks for the first 48 weeks following Day 1 Cycle 1 [cycle length=42 days]; thereafter every 12 weeks until PD or death due to any cause, whichever occurs first [up to approximately 3.5 years])

10. Duration of OR, as Determined by Investigator Using RECIST v1.1

    Time frame: Baseline up to 3.5 years (assessed at Baseline then every 8 weeks for the first 48 weeks following Day 1 Cycle 1 [cycle length=42 days]; thereafter every 12 weeks until PD or death due to any cause, whichever occurs first [up to approximately 3.5 years])

11. Progression-Free Survival (PFS), as Determined by Investigator Using RECIST v1.1

    Time frame: Baseline up to 3.5 years (assessed at Baseline then every 8 weeks for the first 48 weeks following Day 1 Cycle 1 [cycle length=42 days]; thereafter every 12 weeks until PD or death due to any cause, whichever occurs first [up to approximately 3.5 years])

12. Overall Survival (OS)

    Time frame: Baseline up to death due to any cause (up to approximately 3.5 years)

Publications

• Hellmann MD, Kim TW, Lee CB, Goh BC, Miller WH Jr, Oh DY, Jamal R, Chee CE, Chow LQM, Gainor JF, Desai J, Solomon BJ, Das Thakur M, Pitcher B, Foster P, Hernandez G, Wongchenko MJ, Cha E, Bang YJ, Siu LL, Bendell J. Phase Ib study of atezolizumab combined with cobimetinib in patients with solid tumors. Ann Oncol. 2019 Jul 1;30(7):1134-1142. doi: 10.1093/annonc/mdz113. PubMed 30918950 ↗