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Atezolizumab Plus PEGPH20 Versus Chemotherapy in Advanced Pancreatic Ductal Adenocarcinoma and Gastric Cancer:
Andrew H Ko1, Kyu-Pyo Kim2, Jens T Siveke3
1Division of Hematology/Oncology, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
Background:
The MORPHEUS platform comprises multiple open-label, randomized, phase Ib/II trials designed to identify early efficacy and safety signals of treatment combinations across cancers. Atezolizumab (anti-programmed cell death 1 ligand 1 [PD-L1]) was evaluated in combination with PEGylated recombinant human hyaluronidase (PEGPH20).
Methods:
In 2 randomized MORPHEUS trials, eligible patients with advanced, previously treated pancreatic ductal adenocarcinoma (PDAC) or gastric cancer (GC) received atezolizumab plus PEGPH20, or control treatment (mFOLFOX6 or gemcitabine plus nab-paclitaxel [MORPHEUS-PDAC]; ramucirumab plus paclitaxel [MORPHEUS-GC]). Primary endpoints were objective response rates (ORR) per RECIST 1.1 and safety.
Results:
In MORPHEUS-PDAC, ORRs with atezolizumab plus PEGPH20 (n = 66) were 6.1% (95% CI, 1.68%-14.80%) vs. 2.4% (95% CI, 0.06%-12.57%) with chemotherapy (n = 42). In the respective arms, 65.2% and 61.9% had grade 3/4 adverse events (AEs); 4.5% and 2.4% had grade 5 AEs. In MORPHEUS-GC, confirmed ORRs with atezolizumab plus PEGPH20 (n = 13) were 0% (95% CI, 0%-24.7%) vs. 16.7% (95% CI, 2.1%-48.4%) with control (n = 12). Grade 3/4 AEs occurred in 30.8% and 75.0% of patients, respectively; no grade 5 AEs occurred.
Conclusion:
Atezolizumab plus PEGPH20 showed limited clinical activity in patients with PDAC and none in patients with GC. The safety of atezolizumab plus PEGPH20 was consistent with each agent's known safety profile. (ClinicalTrials.gov Identifier: NCT03193190 and NCT03281369).
Insights
The combination of atezolizumab and PEGPH20 demonstrated limited efficacy in pancreatic cancer and no efficacy in gastric cancer. Safety profiles were consistent with known side effects of each agent.
Area of Science:
- Oncology
- Clinical Trials
- Immunotherapy
Background:
- The MORPHEUS platform investigates novel cancer treatment combinations.
- Atezolizumab (anti-PD-L1) was combined with PEGPH20 for advanced cancers.
Purpose of the Study:
- To evaluate the efficacy and safety of atezolizumab plus PEGPH20 in pancreatic ductal adenocarcinoma (PDAC) and gastric cancer (GC).
Main Methods:
- Two randomized MORPHEUS trials (PDAC and GC) compared atezolizumab + PEGPH20 against control treatments.
- Primary endpoints included objective response rates (ORR) and safety assessments.
Main Results:
- In PDAC, ORRs were 6.1% (atezolizumab + PEGPH20) vs. 2.4% (chemotherapy).
- In GC, ORRs were 0% (atezolizumab + PEGPH20) vs. 16.7% (control).
- Grade 3/4 adverse events were observed in both arms across both trials.
Conclusions:
- Atezolizumab plus PEGPH20 showed minimal clinical activity in PDAC and no activity in GC.
- The safety profile of the combination was consistent with individual agent profiles.
