On May 19, 2021 Arcus Biosciences, Inc. (NYSE:RCUS), an oncology-focused biopharmaceutical company working to create best-in-class cancer therapies, reported initial efficacy and safety data from one of the cohorts in ARC-6, a randomized Phase 1b/2 platform study, evaluating the novel combination of etrumadenant (dual adenosine A2a/A2b receptor antagonist) plus zimberelimab (anti-PD1 antibody) and docetaxel in people with taxane-naïve mCRPC who progressed following treatment with one or more new hormonal agents and were checkpoint inhibitor-naïve (Press release, Arcus Biosciences, MAY 19, 2021, View Source [SID1234580313]). In this Phase 1b cohort of the etrumadenant-based combination, a composite ORR (radiographic and/or PSA [prostate-specific antigen] response) of 41% and a PSA response of 35% were observed. The safety profile was consistent with the known profiles of each individual agent, and no significant additive toxicity was observed with the addition of etrumadenant. These data will be presented in a poster session at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting taking place June 4-8.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We are encouraged by these early data that indicate the etrumadenant-based combination is well tolerated and demonstrates promising clinical activity in people with advanced disease who progressed on prior treatments," said Bill Grossman, M.D., Ph.D., Chief Medical Officer of Arcus. "Based on these data, we have initiated enrollment into the randomized Phase 2 portion of this arm in the ARC-6 platform study, which compares the etrumadenant-based regimen to standard of care."

"Prostate tumors produce high levels of adenosine, which is believed to be immunosuppressive," said Sumit K. Subudhi, M.D., Ph.D., Department of Genitourinary Medical Oncology, Division of Cancer Medicine at the University of Texas, M.D. Anderson Cancer Center. "I am encouraged by the early evidence of clinical response and composite ORR of 41% observed in this study cohort, indicating adenosine receptor blockade with an etrumadenant-based combination may have a role in the treatment of prostate cancer."

ARC-6: A Phase 1b/2, Open-Label, Randomized Platform Study to Evaluate Efficacy and Safety of Etrumadenant (AB928)-Based Treatment Combinations in Patients with Metastatic Castrate-Resistant Prostate Cancer (Abstract 5039)

As of the data cut-off (DCO) of April 9, 2021, 17 people (n=17) had received the etrumadenant-based combination in this cohort of the Phase 1b portion of the study. Median time on treatment was 4.2 months (range: 2.1-8.3+ months), and 11 people remained on study treatment at time of DCO. For this cohort, all people had received prior systemic therapy but were taxane naive; most (13/17; 76%) had received ≥1 prior anti-androgen, and 11/17 people (65%) had received prior abiraterone.

Safety Analyses:

People in this cohort of the study were administered 150 mg of etrumadenant orally once daily plus 360 mg of zimberelimab and 75mg/m2 of docetaxel intravenously every three weeks.
All people experienced treatment emergent adverse events (TEAE), and the most common TEAEs were alopecia (53%), lymphocyte count decreases (53%) and fatigue (47%).
Grade 3 or 4 related TEAEs were reported for 6/17 (35%) people; all of these events were related to etrumadenant and may also be attributed to zimberelimab and/or docetaxel.
No treatment emergent serious adverse events (TESAEs) were considered related to etrumadenant.
Clinical Activity:

The composite ORR (radiographic and/or PSA response) was 41% (7/17) per the Prostate Cancer Working Group 3 (PCWG3) criteria.
Six people (35%) had a >50% decrease in PSA level, and seven people (41%) had non-response/non-progression.
All 11 people with RECIST measurable or non-measurable disease experienced clinical benefit (stable disease or better).
One unconfirmed complete response (CR) was observed in a person with only non-target disease remaining.
Two confirmed partial responses (PRs) were observed; one person with PR also had improvement in bone disease burden.
The safety and clinical activity data from this cohort of ARC-6 add to the emerging body of evidence that adenosine receptor blockade with an etrumadenant-based combination may have a role in the treatment of certain cancers. Based on these results, Arcus has initiated the randomized portion of this cohort which is evaluating this etrumadenant-based combination compared to docetaxel, the current standard of care for this setting.

Additional information about this poster presentation may be found on the Arcus website at Arcus Publications on June 4.

In addition to ARC-6, etrumadenant is currently being evaluated in three randomized Phase 2 studies:

ARC-7 is evaluating domvanalimab (anti-TIGIT antibody) plus zimberelimab vs. zimberelimab alone vs. domvanalimab plus zimberelimab and etrumadenant in first-line metastatic, PD-L1>50%, locally advanced or metastatic non-small cell lung cancer (NSCLC), with an interim analysis planned for this quarter.
ARC-4 is evaluating etrumadenant plus chemotherapy and zimberelimab vs. chemotherapy plus zimberelimab in second-line (2L) or third-line (3L) EGFR-positive NSCLC. Data from this study are expected in the second half of 2021.
ARC-9 is evaluating etrumadenant-based combinations in 2L and 3L metastatic colorectal cancer (mCRC). These data build on the results of ARC-3, a Phase 1/1b open-label study of etrumadenant plus chemotherapy in people with mCRC, which showed encouraging tolerability and efficacy in the 3L setting compared to standard of care. Data from this study are expected in the first half of 2022.
About Etrumadenant

Etrumadenant (AB928), the first dual A2a/A2b adenosine receptor antagonist in the clinic, is designed to maximally inhibit the adenosine-driven impairment of tumor-infiltrating lymphocytes (mainly CD8+ T cells and NK cells) and myeloid cells (dendritic cells, macrophages), mediated by A2aR and A2bR, respectively. A2bR is also upregulated by certain cancer cells, such as in prostate cancer and KRAS-mutated cancers. As a result, etrumadenant may uniquely block adenosine’s immunosuppressive and cancer cell-intrinsic effects. Developed specifically for the oncology setting, etrumadenant achieves high penetration of tumor tissue, robust potency in the presence of high adenosine concentrations, and minimal shift in potency from non-specific protein binding. Etrumadenant has demonstrated a favorable safety profile with a variety of combination regimens and exhibits pharmacokinetics / pharmacodynamics consistent with once-daily oral dosing. AB928 is currently being evaluated in several Phase 1b/2 studies across multiple indications.