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    DRUG:

    limantrafin (CB-103)

    i
    Other names: CB-103, CB103, CB 103
    Company:
    Cellestia Biotech
    Drug class:
    Notch inhibitor
    Related drugs:
    6ms
    Limantrafin-BODIPY Conjugates Reduce Stemness and Metastatic Potential via Superoxide Driven Phototherapy in Triple Negative Breast Cancer. (PubMed, Small)
    This dual action may impair tumor aggressiveness, recurrence, and promote immunogenic cell death. The findings highlight that the conjugation of the Notch1 inhibitor, Limantrafin, with BODIPY widens the horizon of Type-I photosensitizers to design next-generation PDT agents.
    Journal
    |
    NOTCH1 (Notch 1) • ICAM1 (Intercellular adhesion molecule 1)
    |
    limantrafin (CB-103)
    over1year
    Phase II Study to Evaluate Safety and Efficacy of CB-103 With Venetoclax in Adolescent and Young Adult Patients With Relapsed/Refractory T-ALL or T-LBL (clinicaltrials.gov)
    P2, N=2, Terminated, M.D. Anderson Cancer Center | N=30 --> 2 | Trial completion date: Jul 2026 --> Aug 2024 | Recruiting --> Terminated | Trial primary completion date: Jul 2026 --> Aug 2024; The sponsor requested termination due to internal reprioritization of resources.
    Enrollment change • Trial completion date • Trial termination • Trial primary completion date • Combination therapy
    |
    BCL2 (B-cell CLL/lymphoma 2) • CD8 (cluster of differentiation 8) • CD34 (CD34 molecule) • CD5 (CD5 Molecule) • CD7 (CD7 Molecule) • CD2 (CD2 Molecule)
    |
    Venclexta (venetoclax) • limantrafin (CB-103)
    over1year
    CB-103 With Either Lenvatinib or Abemaciclib in Patients With NOTCH ACC (clinicaltrials.gov)
    P1/2, N=34, Recruiting, Glenn J. Hanna | Trial primary completion date: Jun 2024 --> Jun 2025
    Trial primary completion date
    |
    Lenvima (lenvatinib) • Verzenio (abemaciclib) • limantrafin (CB-103)
    almost2years
    CAILA: CB-103 Plus NSAI In Luminal Advanced Breast Cancer (clinicaltrials.gov)
    P2, N=2, Terminated, MedSIR | N=80 --> 2 | Active, not recruiting --> Terminated; Sponsor decision
    Enrollment change • Trial termination • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PGR (Progesterone receptor)
    |
    ER positive • HER-2 negative • PGR positive
    |
    letrozole • anastrozole • limantrafin (CB-103)
    2years
    A Phase I Study of the Pan-Notch Inhibitor CB-103 for Patients with Advanced Adenoid Cystic Carcinoma and Other Tumors. (PubMed, Cancer Res Commun)
    Peripheral downregulation of select Notch target gene levels was observed with escalating doses. Future studies exploring CB-103 should enrich for patients with NOTCH-mutant ACC and investigate rational combinatorial approaches in tumors where there is limited success with investigational or approved drugs.
    P1 data • Journal • Metastases
    |
    NICD (NOTCH1 intracellular domain)
    |
    NOTCH mutation
    |
    limantrafin (CB-103)
    over2years
    Evaluation of the anticancer activity of RIN-1, a Notch signaling modulator, in head and neck squamous cell carcinoma. (PubMed, Sci Rep)
    Here, we present the growth- and differentiation-modulating effects of various "next generation" small molecule Notch modulators represented by RIN-1, and CB-103, on HNSCC, compared to gamma secretase inhibitors as "conventional" NOTCH interfering compounds, like DAPT...In contrast, RIN-1 treatment resulted in inhibition of Notch signalling and the growth of HNSCC spheroids under non-adherent cell culture conditions. Our results suggest that modulation of Notch signalling could be used as a chemotherapeutic agent in selected patients with intact NOTCH signaling.
    Journal
    |
    HES1 (Hes Family BHLH Transcription Factor 1) • CDKN1A (Cyclin-dependent kinase inhibitor 1A) • HEY1 (Hes Related Family BHLH Transcription Factor With YRPW Motif 1)
    |
    limantrafin (CB-103)
    over2years
    The Efficacy of CB-103, a First-in-Class Transcriptional Notch Inhibitor, in Preclinical Models of Breast Cancer. (PubMed, Cancers (Basel))
    our data indicate that CB-103 is an attractive candidate for clinical investigation in endocrine-resistant, recurrent breast cancers with biomarker-confirmed Notch activity in combination with SERDs and/or CDKis and in TNBCs with biomarker-confirmed Notch activity in combination with taxane-containing chemotherapy regimens.
    Preclinical • Journal
    |
    ER (Estrogen receptor)
    |
    ER Y537S • ESR1 mutation
    |
    Ibrance (palbociclib) • paclitaxel • fulvestrant • limantrafin (CB-103)
    over2years
    A Phase 1/2 Study CB-103 With or Without Venetoclax in Patients With NOTCH ACC (clinicaltrials.gov)
    P1/2, N=34, Recruiting, Glenn J. Hanna | Not yet recruiting --> Recruiting
    Enrollment open
    |
    BCL2 (B-cell CLL/lymphoma 2)
    |
    NOTCH mutation
    |
    Venclexta (venetoclax) • Lenvima (lenvatinib) • limantrafin (CB-103)
    over2years
    Metastatic clear-cell renal cell carcinoma: a frequent NOTCH1 mutation predictive of response to anti-NOTCH1 CB-103 treatment. (PubMed, Exp Hematol Oncol)
    We identified a frequent, unexpected pL1575P_c4724T_C NOTCH1 mutation as a new biomarker for ccRCC metastases, predictive of response to the CB103 NOTCH1-intracellular domain inhibitor.
    Journal • Metastases
    |
    NOTCH1 (Notch 1) • NICD (NOTCH1 intracellular domain)
    |
    NOTCH1 mutation • NOTCH1 expression
    |
    limantrafin (CB-103)
    over2years
    Phase II Study to Evaluate Safety and Efficacy of CB-103 With Venetoclax in Adolescent and Young Adult Patients With Relapsed/Refractory T-ALL or T-LBL (clinicaltrials.gov)
    P2, N=30, Recruiting, M.D. Anderson Cancer Center | Not yet recruiting --> Recruiting | Initiation date: Dec 2023 --> Apr 2023
    Enrollment open • Trial initiation date • Combination therapy
    |
    BCL2 (B-cell CLL/lymphoma 2) • CD8 (cluster of differentiation 8) • CD34 (CD34 molecule) • CD5 (CD5 Molecule) • CD7 (CD7 Molecule) • CD2 (CD2 Molecule)
    |
    Venclexta (venetoclax) • limantrafin (CB-103)
    over2years
    A Phase 1/2 Study CB-103 With or Without Venetoclax in Patients With NOTCH ACC (clinicaltrials.gov)
    P1/2, N=34, Not yet recruiting, Glenn J. Hanna
    New P1/2 trial
    |
    BCL2 (B-cell CLL/lymphoma 2)
    |
    NOTCH mutation
    |
    Venclexta (venetoclax) • Lenvima (lenvatinib) • limantrafin (CB-103)
    almost3years
    Phase II Study to Evaluate Safety and Efficacy of CB-103 With Venetoclax in Adolescent and Young Adult Patients With Relapsed/Refractory T-ALL or T-LBL (clinicaltrials.gov)
    P2, N=30, Not yet recruiting, M.D. Anderson Cancer Center | Initiation date: Dec 2022 --> Dec 2023
    Trial initiation date • Combination therapy
    |
    BCL2 (B-cell CLL/lymphoma 2) • CD8 (cluster of differentiation 8) • CD34 (CD34 molecule) • CD5 (CD5 Molecule) • CD7 (CD7 Molecule) • CD2 (CD2 Molecule)
    |
    Venclexta (venetoclax) • limantrafin (CB-103)