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    DRUG:

    zamaporvint (RXC004)

    i
    Other names: RXC004, RXC-004, RXC 004
    Associations

    News

    Trials
    Company:
    Redx
    Drug class:
    PORCN inhibitor
    Related drugs:
    Associations

    News

    Trials
    9d
    Clinical study assessing the preliminary efficacy and safety of RXC004, in Patients with Advanced Pancreatic Cancer that have Progressed following Therapy with Current Standard of Care (ACTRN12624000588594)
    P2, N=20, Not yet recruiting, Australian Genomic Cancer Medicine Centre Ltd t/a Omico
    New P2 trial • Metastases
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    RNF43 (Ring Finger Protein 43)
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    RNF43 mutation
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    zamaporvint (RXC004)
    16d
    PORCUPINE: A Study to Assess Efficacy of RXC004 +/- Nivolumab in Ring Finger Protein 43 (RNF43) or R-spondin (RSPO) Aberrated, Metastatic, Microsatellite Stable, Colorectal Cancer After Progression on Standard of Care (SOC) (clinicaltrials.gov)
    P2, N=25, Completed, Redx Pharma Plc | Recruiting --> Completed | N=50 --> 25 | Trial completion date: Dec 2023 --> Apr 2024 | Trial primary completion date: Aug 2023 --> Apr 2024
    Trial completion • Enrollment change • Trial completion date • Trial primary completion date • Combination therapy • Metastases
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    RNF43 (Ring Finger Protein 43) • RSPO2 (R-Spondin 2)
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    Opdivo (nivolumab) • Prolia (denosumab) • zamaporvint (RXC004)
    4ms
    KEYNOTE-E86: A Study to Assess RXC004 Efficacy in Advanced Solid Tumours After Progression on Standard of Care (SoC) Therapy (PORCUPINE2) (clinicaltrials.gov)
    P2, N=45, Completed, Redx Pharma Plc | Active, not recruiting --> Completed
    Trial completion • Metastases
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    RNF43 (Ring Finger Protein 43)
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    RNF43 mutation
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    Keytruda (pembrolizumab) • Prolia (denosumab) • zamaporvint (RXC004)
    8ms
    KEYNOTE-E86: A Study to Assess RXC004 Efficacy in Advanced Solid Tumours After Progression on Standard of Care (SoC) Therapy (PORCUPINE2) (clinicaltrials.gov)
    P2, N=45, Active, not recruiting, Redx Pharma Plc | Recruiting --> Active, not recruiting | N=80 --> 45 | Trial primary completion date: Jun 2023 --> Nov 2023
    Enrollment closed • Enrollment change • Trial primary completion date • Metastases
    |
    RNF43 (Ring Finger Protein 43)
    |
    RNF43 mutation
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    Keytruda (pembrolizumab) • Prolia (denosumab) • zamaporvint (RXC004)
    10ms
    Therapeutic opportunities for porcupine inhibition in gastrointestinal cancer (ESMO 2023)
    Preclinically, GI tumors with upstream Wnt pathway variants (RNF43 loss of function (LoF), RSPO gain of function (GoF)) are Wnt ligand dependent and exquisitely sensitive to RXC004, a small molecule Porcupine inhibitor...Conclusions Upstream Wnt pathway variants are enriched in GI cancer, in particular Small Bowel cancer, a rare subtype of high unmet need. In MSS CRC cancer, the poor prognosis and high BRAF_V600E co-occurrence with upstream Wnt pathway variants suggests benefit of co-targeting Wnt and MAPK pathways in this population.
    RNF43 (Ring Finger Protein 43) • RSPO2 (R-Spondin 2) • RSPO3 (R-Spondin 3)
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    BRAF V600E • BRAF V600 • BRAF wild-type
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    MI Tumor Seek™
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    zamaporvint (RXC004)
    11ms
    Study to Evaluate the Safety and Tolerability of RXC004 in Advanced Malignancies (clinicaltrials.gov)
    P1, N=46, Active, not recruiting, Redx Pharma Plc | Completed --> Active, not recruiting | Trial completion date: Mar 2023 --> Sep 2023 | Trial primary completion date: Mar 2023 --> Sep 2023
    Enrollment closed • Trial completion date • Trial primary completion date • Combination therapy • Metastases
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    Opdivo (nivolumab) • zamaporvint (RXC004)
    11ms
    Study to Evaluate the Safety and Tolerability of RXC004 in Advanced Malignancies (clinicaltrials.gov)
    P1, N=50, Completed, Redx Pharma Plc | Recruiting --> Completed | Trial completion date: Dec 2021 --> Mar 2023 | Trial primary completion date: Jul 2021 --> Mar 2023
    Trial completion • Trial completion date • Trial primary completion date • Combination therapy • Metastases
    |
    Opdivo (nivolumab) • zamaporvint (RXC004)
    1year
    PORCUPINE: A Study to Assess Efficacy of RXC004 +/- Nivolumab in Ring Finger Protein 43 (RNF43) or R-spondin (RSPO) Aberrated, Metastatic, Microsatellite Stable, Colorectal Cancer After Progression on Standard of Care (SOC) (clinicaltrials.gov)
    P2, N=50, Recruiting, Redx Pharma Plc | Trial completion date: Aug 2023 --> Dec 2023 | Trial primary completion date: Apr 2023 --> Aug 2023
    Trial completion date • Trial primary completion date • Combination therapy • Metastases
    |
    RNF43 (Ring Finger Protein 43) • RSPO2 (R-Spondin 2)
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    Opdivo (nivolumab) • Prolia (denosumab) • zamaporvint (RXC004)
    1year
    The Wnt Pathway Inhibitor RXC004 Blocks Tumor Growth and Reverses Immune Evasion in Wnt Ligand-dependent Cancer Models. (PubMed, Cancer Res Commun)
    RXC004 has demonstrated the potential to block both tumor growth and tumor immune evasion in a genetically defined, clinically actionable subpopulation of Wnt ligand-dependent gastrointestinal cancers. The clinical utility of RXC004, and other Porcupine inhibitors, in such Wnt ligand-dependent cancers is currently being assessed in patient trials.
    Preclinical • Journal • PD(L)-1 Biomarker • IO biomarker
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    CD8 (cluster of differentiation 8) • RNF43 (Ring Finger Protein 43) • RSPO3 (R-Spondin 3)
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    RNF43 mutation
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    zamaporvint (RXC004)
    1year
    Pre-clinical activity of the Wnt/Beta-catenin pathway inhibitor RXC004 in models of biliary tract cancer (AACR 2023)
    Background: RXC004 is a potent and selective inhibitor of the Wnt pathway regulator Porcupine, and is currently being investigated in phase 2 studies in patients with advanced cancers, including Biliary Tract Cancers (BTCs) +/- Pembrolizumab (NCT04907851 and NCT04907539). These data demonstrate that (1) RXC004 is efficacious in pre-clinical PDX models of BTC, (2) RXC004 induces multiple PD effects in BTC models at the level of gene expression, cell proliferation and cell differentiation, and (3) PDX models of BTC can be clustered based on baseline transcriptomic profiles of Wnt signalling genes and predict RXC004 sensitivity.
    Preclinical • PD(L)-1 Biomarker
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    MYC (V-myc avian myelocytomatosis viral oncogene homolog) • RNF43 (Ring Finger Protein 43) • MUC4 (Mucin 4, Cell Surface Associated) • MUC2 (Mucin 2) • MUC5AC (Mucin 5AC)
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    RNF43 mutation • MUC4 expression
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    nCounter® PanCancer IO 360™ Panel • nCounter® PanCancer Pathways Panel
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    Keytruda (pembrolizumab) • zamaporvint (RXC004)
    over1year
    A Study to Assess RXC004 Efficacy in Advanced Solid Tumours After Progression on Standard of Care (SoC) Therapy (PORCUPINE2) (clinicaltrials.gov)
    P2, N=80, Recruiting, Redx Pharma Plc | N=40 --> 80 | Trial completion date: Jun 2023 --> Dec 2023 | Trial primary completion date: Mar 2023 --> Jun 2023
    Enrollment change • Trial completion date • Trial primary completion date • Metastases
    |
    RNF43 (Ring Finger Protein 43)
    |
    RNF43 mutation
    |
    Keytruda (pembrolizumab) • Prolia (denosumab) • zamaporvint (RXC004)
    2years
    A multi-arm, phase 2, open-label study to assess the efficacy of RXC004 as monotherapy and in combination with nivolumab in patients with ring finger protein 43 (RNF43) or R-spondin (RSPO) aberrated, metastatic, microsatellite stable colorectal cancer following standard treatments. (ASCO 2022)
    As Wnt inhibition can affect bone metabolism, patients undergo a screening DEXA scan and receive prophylactic denosumab throughout the treatment period. For Arm B, a TV of 30% ORR is considered clinically significant against a LRV of 10% ORR (Eng, 2019). RXC004 is also being investigated in a second Phase 2 trial, PORCUPINE 2 (NCT04907851), in Biliary Tract Cancers and RNF-43 mutated Pancreatic Cancers.
    Clinical • P2 data • Combination therapy • PD(L)-1 Biomarker
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    RNF43 (Ring Finger Protein 43) • RSPO2 (R-Spondin 2) • RSPO1 (R-Spondin 1)
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    RNF43 mutation
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    Opdivo (nivolumab) • Prolia (denosumab) • zamaporvint (RXC004)
    2years
    Pre-clinical efficacy of the Wnt pathway inhibitor RXC004 in combination with anti-cancer therapies (AACR 2022)
    RXC004, dosed at 5mg/kg QD (5 days on / 2 days off), was evaluated in combination with either the clinically relevant colorectal triplet chemotherapy regimen (5-fluorouracil 5-FU (25mg/kg), irinotecan (50mg/kg) and oxaliplatin (5mg/kg)) or doublet chemotherapy regimen (5-FU (25mg/kg), irinotecan (50mg/kg)). These data demonstrate that RXC004 in combination with clinically relevant standard of care chemotherapy regimens can lead to potential benefit over chemotherapy alone. The RXC004 induced downregulation of DNA repair pathway genes observed in vitro could contribute to the beneficial effect seen in combination with a PARP inhibitor in vitro as well as the combination effect observed in vivo with standard of care chemotherapy agents.
    Preclinical • Combination therapy • BRCA Biomarker • PARP Biomarker
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • RNF43 (Ring Finger Protein 43)
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    BRCA1 mutation • RNF43 mutation • BRCA2 expression
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    5-fluorouracil • oxaliplatin • irinotecan • zamaporvint (RXC004)
    2years
    Precision medicine for pancreatic cancer in the UK national health service: Lessons learned from the Precision-Panc platform (AACR 2022)
    Somatic driver variants in RNF43 were detected in 15 patients (5.8%) (biomarker for PRIMUS-007, a second-line trial of porcupine inhibitor RXC004). Three patients (1.2%) were found to be MSI high and 18 (9.1%) had a TMB ≥ 4mutations/Mb (eligible for PRIMUS-008; Pembrolizumab/ Olaparib for patients with a high TMB)... We present the experience and real-world challenges in longitudinal fashion in delivering precision medicine for PC, with attrition along patient and tissue pathways. The majority of samples were successfully sequenced and embedding research activities into routine clinical practice is enabling drug and biomarker development.PS. Discrepancy of numbers is due to a real time snap shot of the pipeline.
    Tumor Mutational Burden • MSi-H Biomarker • PARP Biomarker • PD(L)-1 Biomarker
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    KRAS (KRAS proto-oncogene GTPase) • TMB (Tumor Mutational Burden) • HRD (Homologous Recombination Deficiency) • RNF43 (Ring Finger Protein 43)
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    TMB-H • MSI-H/dMMR • HRD • KRAS wild-type • RAS wild-type
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    Keytruda (pembrolizumab) • Lynparza (olaparib) • 5-fluorouracil • leucovorin calcium • zamaporvint (RXC004)
    2years
    A Study to Assess RXC004 Efficacy in Advanced Solid Tumours After Progression on Standard of Care (SoC) Therapy (PORCUPINE2) (clinicaltrials.gov)
    P2, N=40, Recruiting, Redx Pharma Plc | Not yet recruiting --> Recruiting
    Enrollment open
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    RNF43 (Ring Finger Protein 43)
    |
    RNF43 mutation
    |
    Prolia (denosumab) • zamaporvint (RXC004)
    over2years
    PORCUPINE: A Study to Assess Efficacy of RXC004 +/- Nivolumab in Ring Finger Protein 43 (RNF43) or R-spondin (RSPO) Aberrated, Metastatic, Microsatellite Stable, Colorectal Cancer After Progression on Standard of Care (SOC) (clinicaltrials.gov)
    P2, N=50, Recruiting, Redx Pharma Plc | Not yet recruiting --> Recruiting | Initiation date: Aug 2021 --> Nov 2021
    Clinical • Enrollment open • Trial initiation date • Combination therapy
    |
    RNF43 (Ring Finger Protein 43) • RSPO2 (R-Spondin 2)
    |
    Opdivo (nivolumab) • Prolia (denosumab) • zamaporvint (RXC004)
    over2years
    A Study to Assess RXC004 Efficacy in Advanced Solid Tumours After Progression on Standard of Care (SoC) Therapy (PORCUPINE2) (clinicaltrials.gov)
    P2, N=40, Not yet recruiting, Redx Pharma Plc | Trial completion date: Feb 2023 --> Jun 2023 | Initiation date: Jun 2021 --> Sep 2021 | Trial primary completion date: Jul 2022 --> Mar 2023
    Clinical • Trial completion date • Trial initiation date • Trial primary completion date
    |
    RNF43 (Ring Finger Protein 43)
    |
    RNF43 mutation
    |
    Prolia (denosumab) • zamaporvint (RXC004)
    almost3years
    Study to Assess the Preliminary Efficacy of RXC004 in Monotherapy and in Combination with Nivolumab, in Patients with Metastatic, Colorectal Cancer who have Progressed following Therapy with Current Standard of Care Estudio para evaluar de manera preliminar la eficacia de RXC004 en monoterapia y en combinación con Nivolumab, en pacientes con cáncer colorrectal metastásico que ha progresado tras el tratamiento de la práctica clínica habitual (clinicaltrialsregister.eu)
    P2, N=60, Ongoing, Redx Pharma Plc
    New P2 trial
    |
    RNF43 (Ring Finger Protein 43)
    |
    Opdivo (nivolumab) • Prolia (denosumab) • zamaporvint (RXC004)
    almost3years
    A Study to Assess RXC004 Efficacy in Advanced Solid Tumours After Progression on Standard of Care (SoC) Therapy (PORCUPINE2) (clinicaltrials.gov)
    P2, N=40, Not yet recruiting, Redx Pharma Plc
    Clinical • New P2 trial
    |
    RNF43 (Ring Finger Protein 43)
    |
    RNF43 mutation
    |
    Prolia (denosumab) • zamaporvint (RXC004)
    almost3years
    PORCUPINE: A Study to Assess Efficacy of RXC004 +/- Nivolumab in Ring Finger Protein 43 (RNF43) or R-spondin (RSPO) Aberrated, Metastatic, Microsatellite Stable, Colorectal Cancer After Progression on Standard of Care (SOC) (clinicaltrials.gov)
    P2, N=50, Not yet recruiting, Redx Pharma Plc
    Clinical • New P2 trial • Combination therapy
    |
    RNF43 (Ring Finger Protein 43) • RSPO2 (R-Spondin 2)
    |
    Opdivo (nivolumab) • Prolia (denosumab) • zamaporvint (RXC004)