PROC (Protein C, Inactivator Of Coagulation Factors Va And VIIIa)

Mirvetuximab soravtansine (MIRV) is an antibody-drug conjugate (ADC) composed of the DM4 payload conjugated to a folate receptor α (FRα)-targeting antibody via the cleavable sulfo-SPDB linker. The MIRV Phase 3 registrational trial (MIRASOL) showed superiority of MIRV vs. chemotherapy (paclitaxel, pegylated liposomal doxorubicin, or topotecan) in patients with high (≥ 75%) FRα-expression PROC, showing an objective response rate of 42% versus 16%, a median progression-free survival of 5.6 versus 4.0 months, and an overall survival of 16.5 versus 12.8 months. Here, we briefly review MIRV mechanism of action, pharmacokinetics, pharmacodynamics, and key clinical efficacy and safety data.

Pulmonary embolism-induced pulmonary arterial hypertension increased right-to-left shunting through the atrial septal patent foramen ovale, contributing to impending paradoxical embolism development at this site. Thrombophilia might be a key risk factor for this venous thrombotic event.

ARM provides valuable insights into the prognosis and the effectiveness of ICI, thereby offering a novel strategy for clinical decision. Baicalin and capsaicin are promising potential drugs for GC treatment.

The addition of afuresertib to paclitaxel did not significantly improve PFS/OS in patients with PROC. However, exploratory biomarker findings suggest potential efficacy in phospho-AKT positive patients, warranting further investigation. The safety/tolerability profile of A + P was consistent with prior AKT-inhibitor studies.

P2, N=230, Recruiting, TORL Biotherapeutics, LLC | Not yet recruiting --> Recruiting

P2, N=230, Not yet recruiting, TORL Biotherapeutics, LLC

Differential expression of sEV proteins distinguishes between GR and PR patients and holds promise as predictive markers for nCRT response and prognosis in patients with LARC. Furthermore, our findings highlight substantial alterations in sEV protein composition following nCRT.

This study highlights the diagnostic, prognostic and immunomodulatory roles of ADH4 in HCC. ADH4 could serve as a valuable biomarker for HCC diagnosis and prognosis, as well as a potential target for immunotherapeutic interventions.

At the current price, MIRV for PROC with high-FRα expression is not the cost-effective strategy in the US. However, its treatment has higher health benefits in bevacizumab-naïve patients, which is likely to be an alternative.

Dual immunotherapy with chemotherapy showed acceptable response rates and tolerable safety in HRR non-mutated PROC, warranting continued clinical investigation.

453 pts with FRα high (Roche FOLR1 Assay) PROC were randomized 1:1 to MIRV 6 mg/kg, adjusted ideal body weight, Day 1 of a 21-day cycle or IC: paclitaxel, pegylated liposomal doxorubicin, or topotecan. MIRV is the first treatment to demonstrate a statistically significant PFS, ORR and OS benefit in PROC compared to IC and demonstrates clinical benefit across subgroups. The efficacy data, along with the well-characterized safety profile, position MIRV as a new, standard of care for pts with FRα positive PROC.

Part 1 is the dose-optimization stage, with ~50 subjects randomized 1:1 at 4.3 mg/kg Q3W or 5.2 mg/kg Q3W + prophylactic pegfilgrastim for 2 cycles followed by 4.3 mg/kg Q3W. Key exclusion criteria: primary platinum refractory disease and prior treatment with a FolRα ADC or ADC-containing tubulin inhibitor. Current Trial Status: Currently enrolling