pulrodemstat (CC-90011)

P1, N=90, Active, not recruiting, Celgene | Phase classification: P1b --> P1 | Trial completion date: Feb 2024 --> Jun 2024 | Trial primary completion date: Feb 2024 --> Jun 2024

P1, N=75, Terminated, Celgene | Trial completion date: Sep 2025 --> Mar 2024 | Active, not recruiting --> Terminated | Trial primary completion date: Sep 2025 --> Mar 2024; Business objectives have changed

Pulrodemstat synergized with Lenvatinib based on suppression of PI3K-AKT signaling and activation of apoptotic signaling.

P2, N=92, Completed, Celgene | Active, not recruiting --> Completed

P1, N=91, Active, not recruiting, Celgene | Trial primary completion date: Aug 2023 --> Sep 2025

The advent of LSD1 inhibitor-based clinical utility began with tranylcypromine, and it is now considered an inevitable scaffold in the search for other irreversible novel LSD1 inhibitors (IMG-7289 or bomedemstat, ORY1001 or iadademstat, ORY-2001 or vafidemstat, GSK2879552, and INCB059872). Moreover, numerous reversible inhibitors for LSD1 have been reported in the literature, including clinical candidates CC-90011 (pulrodemstat) and SP-2577 (seclidemstat)...For the first time, we comprehensively organized the peptide-based LSD1 inhibitors from the design strategy. Peptide inhibitors of LSD1 are classified as H3 peptide and SNAIL1 peptide derivatives, along with miscellaneous peptides that include naturally occurring LSD1 inhibitors.

P1, N=6, Completed, Celgene | Active, not recruiting --> Completed | N=10 --> 6 | Trial completion date: Mar 2025 --> May 2023

The present study preclinically demonstrated that LSD1 inhibition could provide a valuable strategy to enhance PI sensitivity and overcome drug resistance in MM patients and that this combination might be exploited for the treatment of other B-cell malignancies, thus extending the therapeutic impact of the project.

Overall, clinical activity was limited in this pre-treated patient population. No new safety signals emerged, and CC-90011 was well-tolerated in combination with nivolumab. Select biomarker data will be presented.

P2, N=92, Active, not recruiting, Celgene | Trial completion date: Apr 2023 --> Jan 2024 | Trial primary completion date: Apr 2023 --> Jan 2024

P1, N=10, Active, not recruiting, Celgene | Recruiting --> Active, not recruiting

P1, N=10, Recruiting, Celgene | Trial completion date: Aug 2024 --> Mar 2025 | Trial primary completion date: Nov 2022 --> Jul 2023

P1, N=10, Recruiting, Celgene | Trial completion date: Jun 2025 --> Aug 2024

CC-90011 combined with etoposide plus carboplatin or cisplatin was well tolerated in patients with extensive-stage small cell lung cancer (Ponce at al. Preliminary efficacy will be determined using CR rate, rate of CR with partial or incomplete hematologic recovery, overall response rate, and duration of response in parts 1-3, and event-free and overall survival in part 3. Because CC-90011 is expected to target LSCs, its addition to VEN plus AZA is predicted to increase the depth and durability of response by MRD evaluation compared with control, rather than increase remission rates.

P1, N=10, Recruiting, Celgene | Trial completion date: Mar 2025 --> Jun 2025 | Trial primary completion date: Jun 2022 --> Sep 2022

P1, N=10, Recruiting, Celgene | Not yet recruiting --> Recruiting | Trial completion date: Nov 2024 --> Mar 2025 | Initiation date: Dec 2020 --> Jul 2021 | Trial primary completion date: Mar 2022 --> Jun 2022

P1, N=10, Not yet recruiting, Celgene