Tybost (cobicistat)

P1, N=12, Recruiting, Fore Biotherapeutics | Not yet recruiting --> Recruiting

P1, N=12, Not yet recruiting, Fore Biotherapeutics

P4, N=60, Recruiting, Maastricht University Medical Center | Not yet recruiting --> Recruiting

P4, N=350, Not yet recruiting, Gilead Sciences

P=N/A, N=325, Recruiting, National Institute of Allergy and Infectious Diseases (NIAID) | Trial completion date: Oct 2025 --> Mar 2026 | Trial primary completion date: Oct 2025 --> Mar 2026

P2/3, N=130, Recruiting, Gilead Sciences

P2, N=22, Completed, R. Kiplin Guy | Phase classification: P2a --> P2

P1, N=18, Terminated, Gilead Sciences | N=45 --> 18 | Active, not recruiting --> Terminated; Sponsor's decision to change the clinical development plan of this molecule. This decision is not based on efficacy or safety concerns.

An approved BRAFi, when used with MEKi, has ORR 33% with mDOR 13.6=months and ORR=50% with DOR of 6-29 months in V600+ HGG and LGG, respectively (dabrafenib US Prescribing Information, 2023). Phase 1/2a is a single-arm study (NCT02428712) in patients (n=113) with BRAF-altered advanced tumors to assess safety, PK, and efficacy of oral plixorafenib 900-3600 mg/day alone or with cobicistat (CYP3A4/P-gp inhibitor)...Prior anti-cancer treatments included surgery (8/10), radiotherapy (8/10), and systemic therapy (8/10, including temozolomide [n=8], bevacizumab [n=2], carboplatin [n=1], dendritic cell vaccine [n=1])...Plixorafenib has a benign safety profile and leads to a high ORR and durable response in MAPKi-naïve BRAFV600+ PCNST. A phase 2 study is ongoing to confirm these findings (NCT05503797).

Overcoming resistance to paclitaxel by CYP3A5 inhibition may lead to an increased efficacy of the gemcitabine and nab-paclitaxel regimen. Safety, efficacy, PK, and RDE data need to be acquired before investigating this combination in a large-scale clinical study.

P1/2, N=440, Recruiting, Syndax Pharmaceuticals | Trial completion date: Apr 2026 --> Dec 2024 | Trial primary completion date: Apr 2025 --> Dec 2024

Cabozantinib as a single agent should be initiated at 20 mg daily and 60 mg daily when taken concurrently with ARVs that are strong CYP3A4 inhibitors and inducers, respectively, with consideration for subsequent escalation per current cabozantinib guidelines.

The peak dasatinib concentration was successfully increased with cobicistat treatment. Dasatinib and cobicistat cotreatment induced a response in BCR-ABL1 PCR signal, was well tolerated, and led to a substantial reduction in drug costs.

P4, N=60, Not yet recruiting, Maastricht University Medical Center

P2, N=135, Recruiting, Fore Biotherapeutics | Not yet recruiting --> Recruiting | Initiation date: Nov 2022 --> Mar 2023

P1, N=11, Completed, Academisch Ziekenhuis Maastricht | Recruiting --> Completed | N=26 --> 11

Pharmacokinetic boosting of osimertinib with cobicistat in patients with NSCLC is feasible without increasing toxicity, although the degree of boosting is variable.

P2, N=135, Not yet recruiting, Fore Biotherapeutics

P1/2, N=440, Recruiting, Syndax Pharmaceuticals | N=186 --> 440 | Trial completion date: Jan 2024 --> Apr 2026 | Trial primary completion date: Jul 2022 --> Apr 2025

P1 | N=32 | Not yet recruiting | Sponsor: Janssen Research & Development, LLC

No dose adjustment is required for fostemsavir when coadministered with strong CYP3A inhibitors, P-glycoprotein inhibitors, and modest inducers, including regimens with DRV/r, DRV/c, cobicistat, etravirine, and DRV/r plus etravirine based on the therapeutic margin for temsavir (ClinicalTrials.gov registration no. NCT02063360 and NCT02277600).

From the estimated docking scores and MM-GBSA binding energies, six auspicious drug candidates-namely, pibrentasvir, venetoclax, ledipasvir, avatrombopag, cobicistat, and revefenacin-exhibited auspicious binding energies with value < -70.0 kcal/mol. The stabilities of these three promising candidates in complex with ABCG2 transporter were demonstrated by their energetics and structural analyses throughout the 100 ns MD simulations. The current study throws new light on pibrentasvir, venetoclax, and ledipasvir as curative options for multidrug resistant cancers by inhibiting ABCG2 transporter.

P1, N=26, Recruiting, Academisch Ziekenhuis Maastricht | Not yet recruiting --> Recruiting | Trial completion date: Dec 2019 --> Dec 2021 | Trial primary completion date: Oct 2019 --> Oct 2021

Enrolment was prematurely stopped because of the approval of alectinib, a next-generation ALK-inhibitor with superior efficacy. Neither safety signals nor serious adverse events occurred. Pharmacoenhancement with cobicistat as an alternative for dose individualisation for patients with NSCLC with low crizotinib exposure appears to be safe and is cost-effective and feasible.