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Etigilimab (MPH313)

For the potential treatment of patients with advanced or metastatic solid tumors. Etigilimab is an antibody against TIGIT (T-cell immunoreceptor with Ig and ITIM domains). TIGIT is a next generation checkpoint receptor shown to block T-cell activation and the body’s natural anti-cancer immune response. Etigilimab is an IgG1 monoclonal antibody which binds to the human TIGIT receptor on immune cells with a goal of improving the activation and effectiveness of T-cell and NK cell anti-tumor activity.

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The TIGIT immune receptor is a promising new target for cancer immunotherapy. We welcome the opportunity to collaborate with Mereo to jumpstart the clinical assessment of etigilimab in clear cell ovarian cancer, which lacks effective treatment options once advanced."

Ross Barrett, Managing Director, Cancer Focus Fund

Clinical Status

Mereo completed a Phase 1a dose escalation clinical trial with Etigilimab in patients with advanced solid tumors and enrolled patients in a Phase 1b study in combination with nivolumab in selected tumor types.

23 patients were treated in the Phase 1a dose escalation study with doses up to 20 mg/kg Q2W. Tumor types included colorectal cancer, endometrial cancer, pancreatic cancer and other tumors. No dose limiting toxicities were observed. In the Phase 1b combination study, a total of ten patients, nine of whom had progressed on prior anti-PD-1/PD-L1 therapies were enrolled at doses of 3, 10, and 20 mg/kg. Eight patients were evaluable for tumor growth assessment, and all of these patients had progressed on PD-1/PD-L1 therapies with best responses including one patient with a partial response another with stable disease. These patients remained on study for up to 224 days. No dose limiting toxicities (DLTs) were observed and the most common related adverse events included fatigue, rash, and pruritis.

ACTIVATE, a Phase 1b/2 basket combination study of etigilimab in combination with nivolumab in select recurrent advanced / metastatic solid tumors was initiated in March 2021. The multicenter study is designed to evaluate the efficacy, safety, tolerability, PK, and pharmacodynamics of etigilimab, in combination with nivolumab, with dosing every two weeks.

As of September 12, 2022, there were 63 efficacy-evaluable checkpoint inhibitor-naïve (CPI-naive) subjects with a minimum of 1 staging scan at 8 (+/-1) weeks and RECIST 1.1 response assessment or documented clinical progression. Key updates:

Cervical cancer: 3/7 PD-L1 combined positive score CPS>1%, CPI-naïve cervical cancer subjects with confirmed complete responses (cCRs) ORR of 43%, 2 ongoing at >284 days and >142 days, and 1 withdrew consent with ongoing cCR at 163 days. Two additional patients had stable disease (SD) for a DCR rate of 71%. Of interest, biomarker analysis showed that the 2 cervical subjects with complete responses exhibited higher levels of PVR, TIGIT as well as high CD226+CD8+ co-expression. No evaluable tissue for biomarker analysis was available for the third patent with a complete response.

Uveal melanoma: 1/6 evaluable subjects, with confirmed partial response (cPR) at >347 days, ORR 17% and 2 patients were SD, for 175 and 294 days DCR 50%. The subject with cPR was noted to have high CD226+CD8+ co-expression, and was PVR positive and PD-L1 negative (CPS <1%).

Biomarker data presented at ESMO 2022 evaluated tumors for baseline expression of PVR, TIGIT, PD-L1 and CD226 by multiple modalities including validated IHC assays. Consistent with Mereo’s previously reported data (Mereo BioPharma webcast,  November 30, 2021), high PVR expression was observed in subjects with decreases in target lesions (TL) from baseline and RECIST 1.1 responses. Additional noteworthy responses observed in subjects with cancer types not typically responsive to CPI monotherapy, with tumors  that had  high PVR expression and were either PD-L1 negative (CPS <1%), or PD-L1 low (CPS≤3%)  include, (i) an ovarian PR (-80% target lesion (TL) decrease, ongoing >255 days, PD-L1 negative), (ii) an endometrial PR (-69% TL decrease, ongoing >150 days, MMR proficient, PD-L1 CPS=3%), (iii) a dedifferentiated liposarcoma PR (-80% TL decrease, ongoing cPR >267 days, high TIGIT, PD-L1 CPS=1%), and (iv) a recurrent/metastatic testicular GCT patient with stable, near normalization of elevated tumor marker alpha feto protein (doing well clinically on study >127 days), PD-L1 negative. The presentation at ESMO 2022 demonstrated robust target engagement in patients as evidenced by significant decreases in peripheral T regulatory cells while maintaining circulation levels of CD8 cells.  Increases in proliferating T-cells subsets (CD8, CD4), proliferating NK cells, and intracellular cytokines (IFNg, IL2, and TNFa) were observed and sustained longitudinally. Additionally, etigilimab plus nivolumab reduced TPEX cells (CD8+CCR7+PD1+TIGIT+), progenitor cells believed to be committed to an exhausted-like fate. Further data was reported showing reductions in circulating tumor DNA (ctDNA) measured at ~5-6 weeks post-treatment correlated with clinical benefit.

These data support the role of dual checkpoint inhibition of the TIGIT/PVR and PD-(L)-1 pathways and further evaluation of these biomarkers, including PVR and CD226, as a potential enrichment strategy for the treatment of etigilimab plus anti-PD1.

Enrolment in the Phase 1b/2 ACTIVATE trial has been paused; 30 patients previously enrolled currently remain on study. The totality of emerging data from ACTIVATE and other trials targeting the TIGIT axis will direct next steps for the etigilimab program.

Etigilimab news

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Mereo BioPharma Reports Clinical Update and Interim Biomarker Analysis Presented at ESMO 2022 from ACTIVATE Phase 1b/2 Open Label Study of Etigilimab (Anti-TIGIT Antibody MPH-313) plus Nivolumab (Anti-PD-1 Antibody) in Solid Tumors
12 September 2022

Mereo BioPharma Group today reported updated clinical data and promising biomarker data from ACTIVATE, a Phase 1b/ 2 study of anti-TIGIT antibody, etigilimab, in combination with nivolumab, in select recurrent advanced / metastatic solid tumors. These biomarker data were presented at a poster session at the 2022 European Society of Medical Oncology (ESMO) Annual Meeting on September 10, 2022.

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Mereo BioPharma To Present Data Update for the Phase 1b/2 Study (ACTIVATE) of Etigilimab and Nivolumab at 2022 ASCO Annual Meeting; Mereo Also Updates Capital Allocation and Portfolio Prioritization Plan
02 June 2022

Mereo BioPharma today announced updated clinical data from its open-label Phase 1b/2 Study of Etigilimab and Nivolumab in subjects with Select Locally Advanced or Metastatic Solid Tumors (ACTIVATE). The data will be presented in a poster session at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting on June 5, 2022. The Company also provided an update on its capital allocation and portfolio prioritization plan.

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Mereo BioPharma Announces the Presentation of Updated Data From a Phase 1b/2 Study of Etigilimab as a Poster at the 2022 American Society of Clinical Oncology Annual Meeting
26 May 2022

Mereo BioPharma today announced the presentation of interim clinical data from its Phase 1b/2 Study of Etigilimab and Nivolumab in Subjects with Select Locally Advanced or Metastatic Solid Tumors in a poster at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting taking place June 3 – 7, 2022 in Chicago IL.

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Mereo BioPharma Reports Interim Data from ACTIVATE Phase 1b/2 Open Label Study of etigilimab Anti-TIGIT Antibody in combination with Nivolumab in Solid Tumors
30 November 2021

Mereo BioPharma today reported promising interim efficacy, safety, and biomarker data on patients from ACTIVATE, a Phase 1b/2 study of its anti-TIGIT antibody, etigilimab, in combination with nivolumab in select recurrent advanced / metastatic solid tumors

Scientific Publications