On May 19, 2021 The Janssen Pharmaceutical Companies of Johnson & Johnson reported new data from the fixed-duration cohort of the investigational Phase 2 CAPTIVATE study (PCYC-1142), showing 95 percent of patients treated with fixed duration combined IMBRUVICA (ibrutinib) plus venetoclax were alive and progression-free at two years (Press release, Johnson & Johnson, MAY 19, 2021, View Source;Based-Combination-Regimen-as-a-Fixed-Duration-First-Line-Treatment-for-Chronic-Lymphocytic-Leukaemia-Demonstrates-High-Rates-of-Disease-Control [SID1234580316]).1 Deep remissions were seen across all subgroups, including patients with high risk chronic lymphocytic leukaemia (CLL).1 In addition, long-term data from the RESONATE-2 (PCYC-1115/1116) study will be presented, providing the longest follow-up Phase 3 data for any Bruton tyrosine kinase (BTK) inhibitor to date.2 These data reinforce the long-term survival benefits and well-established safety profile of single-agent ibrutinib for patients with CLL, a type of non-Hodgkin lymphoma and the most common form of leukaemia in adults.1,2

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!

Both studies will be presented during the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, June 4-8, and following at the 26th European Hematology Association (EHA) (Free EHA Whitepaper) Congress, June 9-17.

"Ibrutinib was the first BTK inhibitor approved in Europe and has been used to treat more than 230,000 patients worldwide. It is now also the first BTK inhibitor to be studied as a fixed-duration combination treatment option," said Edmond Chan, EMEA Therapeutic Area Lead Haematology, Janssen-Cilag Ltd. "The latest data to be presented at ASCO (Free ASCO Whitepaper) reinforce the potential of ibrutinib as a foundational treatment option across the CLL landscape and add to the breadth of evidence regarding its efficacy and safety profile."

First Data from the Fixed-Duration Cohort of the Phase 2 CAPTIVATE (PCYC-1142) Study of Ibrutinib-Based Combination Regimen in Previously Untreated CLL Patients (Abstract #7501)1

The CAPTIVATE study evaluated previously untreated patients with CLL who were 70 years or younger, including patients with high-risk disease.1 In the fixed-duration cohort (N=159; median age 60 years), patients received three cycles of ibrutinib lead-in therapy, followed by 12 cycles of combination ibrutinib plus venetoclax therapy, and then stopped therapy regardless of minimal residual disease (MRD) status.1 More than 90 percent of patients completed planned therapy of ibrutinib plus venetoclax treatment.

At a median follow-up of 27.9 months, the complete response (CR) rate in the overall population was 56 percent (n=88; 95 percent Confidence Interval [CI]: 48–64) and was consistent across high-risk subgroups.1 Of the patients who achieved a CR, 89 percent had a durable CR of at least one year.1 Among the remaining 11 percent, one patient had progressive disease; the remaining patients with response follow-up of less than one year were not evaluable.1 The overall response rate (ORR) was 96 percent.1 Estimated 24-month progression-free survival (PFS) with ibrutinib plus venetoclax was 93 percent for patients with unmutated IGHV and 97 percent for patients with mutated IGHV (unmutated IGHV 95 percent CI: 85‒97; mutated IGHV 95 percent CI: 88‒99) and overall survival (OS) was 98 percent (95 percent CI: 94-99) for all treated patients.1 Seventy-seven and 60 percent of patients achieved undetectable minimal residual disease (uMRD) at any time in the peripheral blood and bone marrow, respectively.1

"The use of continuous treatment with ibrutinib in CLL has well been established as the standard of care for patients, including those with high-risk disease," said Paolo Ghia*, M.D., Ph.D., Professor of Medical Oncology, Università Vita-Salute San Raffaele, Italy and principal study investigator. "The latest data from the CAPTIVATE study underscore that ibrutinib in an all-oral fixed duration combination with venetoclax also delivers a high rate of progression-free survival at two years while enabling treatment-free remission for patients."

Of note, 94 percent of patients with high baseline tumour lysis syndrome (TLS) risk based on tumour burden shifted to medium- or low-risk after ibrutinib lead-in therapy, and no TLS events occurred.1 Adverse events (AEs) were primarily Grade 1/2.1 The most common Grade 3/4 AEs were neutropaenia (33 percent), infections (eight percent), hypertension (six percent), and neutrophil count decrease (five percent).1 Discontinuations due to AEs were infrequent (three percent for ibrutinib).1

Findings from the uMRD-guided cohort of the CAPTIVATE study were presented at the 2020 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting. The phase 3 GLOW study (NCT03462719) is also evaluating fixed-duration ibrutinib plus venetoclax, with a comparison to chlorambucil plus obinutuzumab, for first-line treatment of younger unfit patients or elderly patients with CLL, regardless of fitness criteria. These studies are part of a comprehensive development programme exploring the potential of ibrutinib-based fixed-duration therapy.

Long-Term Data from the Phase 3 RESONATE-2 Study Demonstrate Efficacy and Safety of Single-Agent Ibrutinib in Previously Untreated CLL Patients (Abstract #7523)2

The RESONATE-2 study evaluated 269 previously untreated patients with CLL aged 65 years or older, without del(17p), who were randomly assigned to receive continuous ibrutinib or chlorambucil up to 12 cycles.2 With up to seven years of follow-up, PFS benefit with single-agent ibrutinib was sustained (PFS Hazard Ratio [HR] 0.160 [95 percent CI: 0.111–0.230]).2 At 6.5 years, the median PFS with ibrutinib has not been reached; 61 percent of patients treated with single-agent ibrutinib were alive and progression-free compared with nine percent of patients treated with chlorambucil.2 The PFS benefit for patients treated with ibrutinib was seen in all subgroups, including those with high-risk genomic features of TP53 mutation, unmutated IGHV or 11q deletion (HR 0.091 [95 percent CI: 0.054–0.152]).2 Additionally, 78 percent of patients in the ibrutinib treatment-arm were alive at 6.5 years. The CR rate with ibrutinib treatment has increased over time to 34 percent.2 Nearly half of patients continue to receive ibrutinib treatment with up to seven years of follow-up.2

Single-agent ibrutinib was well tolerated as a long-term treatment with no new safety signals.2 Ongoing rates of Grade 3 or higher AEs of interest remained low for hypertension (five-to-six-year interval: n=20; six-to-seven-year interval: n=15) and atrial fibrillation (five-to-six-year interval: n=7; six-to-seven-year interval: n=5).2 Additionally, no Grade 3 or higher major haemorrhage occurred in the five-to-seven-year interval.2 Any-grade AEs leading to discontinuations were seen in three percent (n=2) of patients from year five to year six and no patients discontinued treatment in the ibrutinib arm due to AEs from year six to year seven.2

"The positive results from the CAPTIVATE study demonstrate the potential of ibrutinib and venetoclax, with complementary mechanisms of action, to provide deep responses with a once-daily, fixed-duration combination that can be administered in the outpatient setting for younger, fit patients," said Craig Tendler, M.D., Vice President, Clinical Development and Global Medical Affairs, Oncology, Janssen Research & Development, LLC. "The results from RESONATE-2 further support the long-term benefit of ibrutinib monotherapy in front line CLL for which the breadth and maturity of data continue to grow in support of this standard-of-care treatment and its impact on progression free and overall survival."

#ENDS#

About Ibrutinib

Ibrutinib is a once-daily, first-in-class Bruton’s tyrosine kinase (BTK) inhibitor that is administered orally, and is jointly developed and commercialised by Janssen Biotech, Inc. and Pharmacyclics LLC, an AbbVie company.3 Ibrutinib blocks the BTK protein; the BTK protein sends important signals that tell B cells to mature and produce antibodies. BTK signalling is needed by specific cancer cells to multiply and spread.4 By blocking BTK, ibrutinib may help move abnormal B cells out of their nourishing environments in the lymph nodes, bone marrow, and other organs.5

Ibrutinib was first approved by the European Commission (EC) in 2014, and approved indications to date include:3

Chronic lymphocytic leukaemia (CLL): As a single agent or in combination with rituximab or obinutuzumab for the treatment of adult patients with previously untreated CLL, and as a single agent or in combination with bendamustine and rituximab (BR) for the treatment of adult patients with CLL who have received at least one prior therapy.
Mantle cell lymphoma (MCL): As a single agent for the treatment of adult patients with relapsed or refractory MCL.
Waldenström’s macroglobulinemia (WM): As a single agent for the treatment of adult patients who have received at least one prior therapy or in first-line treatment for patients unsuitable for chemo-immunotherapy, and in combination with rituximab for the treatment of adult patients.
Ibrutinib is approved in more than 100 countries, and, to date, has been used to treat more than 230,000 patients worldwide.6 Ibrutinib is the only BTKi that has demonstrated overall survival benefits in three CLL clinical trials, with response durability persisting up to 8 years,7,8,9 and more than seven out of ten patients alive and without disease progression after six and a half years.2 Ibrutinib is the only BTKi that has been shown to mediate short- and long-term immune restoration.10

Ibrutinib is the most comprehensively studied BTKi, with more than 150 active clinical trials in several blood cancers and other serious diseases. For a full list of side effects and information on dosage and administration, contraindications and other precautions when using ibrutinib please refer to the Summary of Product Characteristics for further information.

About Chronic Lymphocytic Leukaemia

Chronic lymphocytic leukaemia (CLL) is typically a slow-growing blood cancer of the white blood cells.11 The overall incidence of CLL in Europe is approximately 4.92 cases per 100,000 persons per year and is about 1.5 times more common in men than in women.12 CLL is predominantly a disease of the elderly, with a median age of 72 years at diagnosis.13

The disease eventually progresses in the majority of patients, and they are faced with fewer treatment options with each relapse. Patients are often prescribed multiple lines of therapy as they relapse or become resistant to treatments.

On May 19, 2021 NANOBIOTIX (Euronext : NANO –– NASDAQ: NBTX – the ‘‘Company’’), a late-clinical stage biotechnology company pioneering physics-based approaches to expand treatment possibilities for patients with cancer, reported the upcoming presentation of updated results from the Company’s priority development pathways in head and neck cancer (head and neck squamous cell carcinoma; HNSCC) and in immunotherapy for advanced cancers at the 2021 Annual Meeting of the American Society for Clinical Oncology (ASCO) (Free ASCO Whitepaper) (Press release, Nanobiotix, MAY 19, 2021, View Source [SID1234580315]). The Company will also present a poster with long-term safety analysis from its pivotal phase II/III study in soft tissue sarcoma.

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!

"The data we will present at ASCO (Free ASCO Whitepaper) provide further support for the paradigm-shifting potential of NBTXR3 as a foundational solid tumor-agnostic and combination-agnostic cancer therapeutic," said Laurent Levy, co-founder and chief executive officer of Nanobiotix. "We are excited to present both long-term safety data from our phase III soft tissue sarcoma study, along with updated safety and efficacy data from our second single-agent registration pathway in head and neck cancer. Moreover, we are particularly eager to present a growing body of data suggesting that after activation by radiotherapy, NBTXR3 may prime an immune response that could enhance the efficacy of immune checkpoint inhibitors as a first-line therapy, overcome resistance for refractory patients, and meaningfully expand the tumor types that respond to the class by transforming cold tumors into hot tumors."

Local Control as a Single-Agent for Patients with Head and Neck Cancer

Abstract #6051: Phase I Dose Expansion Study of Functionalized Hafnium Oxide Nanoparticles (NBTXR3) in Cisplatin-Ineligible Locally Advanced HNSCC Patients

The number of elderly patients diagnosed with locally advanced HNSCC (LA-HNSCC) is increasing. While concurrent chemoradiation is the non-surgical standard of care, not all patients can tolerate platinum-based chemotherapy (e.g., cisplatin). The Nanobiotix phase I dose expansion study in patients with LA-HNSCC (Study 102) is evaluating a single dose of NBTXR3 at 22% of baseline tumor volume (the recommended phase II dose; RP2D). Primary endpoints of the study are objective response rate (ORR) and complete response rate (CRR) of the primary tumor. Study 102 is expected to recruit a total of 44 evaluable patients. To date, 52 total patients have been injected with NBTXR3 in the study overall, of which 40 have been evaluable.

Updated data presented at ASCO (Free ASCO Whitepaper) further support NBTXR3 administration, followed by activation with radiotherapy, as feasible and well-tolerated. Six (6) serious adverse events (SAEs) related to NBTXR3 were observed across five (5) patients. A total of ten (10) deaths related to adverse events were reported. Four (4) deaths related to radiotherapy were observed, along with one (1) death from sepsis that was investigator-assessed as possibly related to NBTXR3, radiotherapy, and cancer.

At a median follow up of 8.1 months, evaluable patients demonstrated a high primary tumor ORR of 82.5% and a 62.5% CRR. These results are consistent with those observed in the dose escalation part of the study and suggest durability of efficacy.

Nanobiotix plans to launch a pivotal phase III global registration trial evaluating NBTXR3 as a single-agent activated by radiotherapy for patients with LA-HNSCC in 2021.

Priming Immune Response and Immunotherapy Combination Across Oncology

Abstract #2590: A Phase I Study of NBTXR3 Activated by Radiotherapy for Patients with Advanced Cancers Treated with an Anti-PD-1 Therapy
Abstract #2591: Overcoming Resistance to Anti-PD-1 with Tumor-Agnostic NBTXR3: From Bench to Bedside

Cancer immunotherapies such as anti-PD-1 have shown promising clinical outcomes over the past two decades and are often used to treat advanced cancers once other therapies have reached the end of their effectiveness. However, across tumor indications, the significant majority of patients (80-85% according to published data) receive only a temporary benefit from anti-PD-1—or no benefit at all—as they either develop resistance to the therapy over time or are non-responsive to treatment altogether.

Previously reported data from the Company’s phase I immunotherapy study in advanced cancers (Study 1100) and its preclinical collaboration with The University of Texas MD Anderson Cancer Center support NBTXR3 activated by radiotherapy as a potential primer of immune response. These data suggest that when combined with anti-PD-1, NBTXR3 could contribute to tumor regression in patients with advanced and metastatic tumors regardless of the patient’s prior exposure to anti-PD-1.

Nanobiotix will provide an update on Study 1100 with additional patients and further follow up prior to the conference (abstract #2590). The Company will also present a compilation of preclinical and clinical data supporting NBTXR3 as a potentially tumor-agnostic, therapeutic combination-agnostic agent that could overcome resistance to immune checkpoint inhibitors and increase response rates across tumor indications (abstract #2591).

Local Control as a Single-Agent for Patients with Soft Tissue Sarcoma

Abstract #11544: Long-Term Evaluation of the Novel Radioenhancer NBTXR3 plus Radiotherapy in Patients with Locally Advanced Soft Tissue Sarcoma Treated in the Phase III Act.in.Sarc Trial

A long-term safety analysis following the Nanobiotix phase II/III pivotal study evaluating NBTXR3 as a single-agent activated by radiotherapy in patients with locally advanced soft tissue sarcoma (STS) did not observe a negative impact on patient quality of life and long-term morbidity. The long-term safety profile of NBTXR3, together with its efficacy data, further supported a favorable benefit-risk ratio for patients with STS. The analysis highlighted potential for future indications, including non-resectable sarcoma, pediatric tumors, and re-irradiation.

Nanobiotix Investor Event

Nanobiotix will host a virtual investor event featuring several key opinion leaders, including study investigators, after the ASCO (Free ASCO Whitepaper) Annual Meeting on Friday, June 11, 2021 at 8 am ET. The discussion will expand on the new immunotherapy results from Study 1100 that will be reported prior to ASCO (Free ASCO Whitepaper), providing additional detail and clinical perspective, following the ASCO (Free ASCO Whitepaper) presentation. Register here.

***

About NBTXR3

NBTXR3 is a novel, potentially first-in-class oncology product composed of functionalized hafnium oxide nanoparticles that is administered via one-time intratumoral injection and activated by radiotherapy. The product candidate’s physical mechanism of action (MoA) is designed to induce significant tumor cell death in the injected tumor when activated by radiotherapy, subsequently triggering adaptive immune response and long-term anti-cancer memory. Given the physical MoA, Nanobiotix believes that NBTXR3 could be scalable across any solid tumor that can be treated with radiotherapy and across any therapeutic combination, particularly immune checkpoint inhibitors.

NBTXR3 is being evaluated in locally advanced head and neck squamous cell carcinoma (HNSCC) as the primary development pathway. The company-sponsored phase I dose escalation and dose expansion study has produced favorable safety data and early signs of efficacy; and a phase III global registrational study is planned to launch in 2021. In February 2020, the United States Food and Drug Administration granted regulatory Fast Track designation for the investigation of NBTXR3 activated by radiation therapy, with or without cetuximab, for the treatment of patients with locally advanced HNSCC who are not eligible for platinum-based chemotherapy—the same population being evaluated in the planned phase III study.

Nanobiotix has also prioritized an Immuno-Oncology development program—beginning with a Company-sponsored phase I clinical study evaluating NBTXR3 activated by radiotherapy in combination with anti-PD-1 checkpoint inhibitors for patients with locoregional recurrent or recurrent/metastatic HNSCC and lung or liver metastases from any primary cancer eligible for anti-PD-1 therapy.

Given the Company’s focus areas, and balanced against the scalable potential of NBTXR3, Nanobiotix has engaged in a strategic collaboration strategy with world class partners to expand development of the product candidate in parallel with its priority development pathways. Pursuant to this strategy, in 2019 Nanobiotix entered into a broad, comprehensive clinical research collaboration with The University of Texas MD Anderson Cancer Center to sponsor several phase I and phase II studies to evaluate NBTXR3 across tumor types and therapeutic combinations.

On May 19, 2021 Puma Biotechnology, Inc. (NASDAQ: PBYI), a biopharmaceutical company, announced publication of three abstracts on neratinib for the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, to be held virtually from June 4-8, 2021 (Press release, Puma Biotechnology, MAY 19, 2021, View Source [SID1234580314]). Puma will present three posters with audio recordings, the corresponding abstracts of which are now live on the 2021 ASCO (Free ASCO Whitepaper) Annual Meeting website. The full posters will be available on the Puma and ASCO (Free ASCO Whitepaper) websites at approximately 9:00 a.m. EDT on June 4, 2021.

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!

Poster Session: Breast Cancer—Local/Regional/Adjuvant

Abstract 540: Association between treatment duration and overall survival in early-stage HER2+ breast cancer patients receiving extended adjuvant therapy with neratinib in the ExteNET trial.
B Moy, M Takahashi, S Ohtani, E Chmielowska, N Yamamoto, B Coudert, F Xu, A Wong, A Chan
Abstract 536: Dose escalation for mitigating diarrhea: Ranked tolerability assessment of antidiarrheal regimens in patients receiving neratinib for early-stage breast cancer.
G Marx, AJ Chien, JA García-Sáenz, A Chan, M Ruiz-Borrego, CH Barcenas, M Thirlwell, M Trudeau, R Bose, D Egle, B Pistilli, J Wasserman, KA Cheong, D Semsek, C Singer, D Hunt, U Khambholja, F Xu, N Shah, A Brufsky
Poster Session: Lung Cancer—Non-Small Cell Metastatic

Abstract 9068: Neratinib efficacy in a subgroup of patients with EGFR exon 18-mutant non-small cell lung cancer (NSCLC) and central nervous system (CNS) involvement: findings from the SUMMIT basket trial.
JW Goldman, SV Ramírez, A Mahipal, JM Suga, LD Eli, AS Lalani, R Bryce, F Xu, N Shah, F Kabbinavar, V Boni, B Haley
The abstracts are available online at: asco.org/abstracts

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.

On May 19, 2021 Scholar Rock (NASDAQ: SRRK), a clinical-stage biopharmaceutical company focused on the treatment of serious diseases in which protein growth factors play a fundamental role, reported a trials in progress poster presentation at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, being held virtually from June 4-8, 2021 (Press release, Scholar Rock, MAY 19, 2021, View Source [SID1234580312]).

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!

The DRAGON Phase 1 proof-of-concept trial (NCT04291079) is evaluating SRK-181, a selective inhibitor of TGFβ1 activation, in patients with locally advanced or metastatic solid tumors that have shown primary resistance to checkpoint inhibitor therapies. Dose escalation is progressing in Part A of the trial and the Company expects to advance to the Part B dose expansion portion of the trial in mid-2021.

The trials in progress e-poster will provide an overview of the design of the DRAGON Phase 1 trial and highlight the biomarker analysis being implemented to support the trial. Details of the poster presentation are as follows:

Session: Developmental Therapeutics–Molecularly Targeted Agents and Tumor Biology
Title: "First-in-Human Phase 1 Trial (DRAGON) of SRK-181: A Potential First-in-Class Selective Latent TGFβ1 Inhibitor, Alone or in Combination with Anti-PD-(L)1 Treatment in Patients with Advanced Solid Tumors" (TPS3146)
Date and Time: Friday, June 4, 11:00 AM – 2:00 PM EDT; Poster sessions available on demand in meeting library beginning 9:00 AM EDT on June 4, 2021.
About SRK-181

SRK-181 is a selective inhibitor of TGFβ1 activation and is an investigational product candidate being developed to overcome primary resistance to checkpoint inhibitor therapy, such as anti-PD-(L)1 antibodies. TGFβ1 is the predominant TGFβ isoform expressed in many human tumor types. Based on analyses of various human tumors that are resistant to anti-PD-(L)1 therapy, data suggest TGFβ1 is a key contributor to the immunosuppressive tumor microenvironment, excluding and preventing entry of cytotoxic T cells into the tumor, thereby inhibiting anti-tumor immunity (1). Scholar Rock believes SRK-181, which specifically targets the latent TGFβ1 isoform, has the potential to overcome this immune cell exclusion and induce tumor regression when administered in combination with anti-PD-(L)1 therapy while potentially avoiding toxicities associated with non-selective TGFβ inhibition. The DRAGON Phase 1 proof-of-concept clinical trial (NCT04291079) in patients with locally advanced or metastatic solid tumors is ongoing. The efficacy and safety of SRK-181 have not been established. SRK-181 has not been approved for any use by the FDA nor any other regulatory agency.

(1) Martin et al., Sci. Transl. Med. 12: 25 March 2020