Sequential Phase II clinical trials evaluating CRLX101 as monotherapy and in combination with bevacizumab in recurrent ovarian cancer.

Abstract

BACKGROUND:

Topoisomerase-1 inhibitors are an important class of cytotoxics associated with toxicity that limits their use. CRLX101 is a novel cyclodextrin-containing polymer conjugate of camptothecin (CPT) that self-assembles into nanoparticles to deliver sustained levels of active CPT into cancer cells while substantially reducing systemic exposure.

METHODS:

We conducted sequential phase II, open label, single arm clinical trials to evaluate CRLX101 as a single agent (n = 29) and with bevacizumab (Bev) (n = 34). Patients (pts) had measurable recurrent epithelial ovarian, tubal or primary peritoneal cancer, that could be platinum refractory, resistant or sensitive. Cohort A (Single agent CRLX101) allowed up to 3 prior chemotherapy regimens, but no prior topo-1 inhibitors. Pts received CRLX101 15 mg/m2 IV every 14 days Q28 with response evaluation every 2 cycles. Cohort B also received Bev 10 mg/kg D1,15 Q28, and included only platinum resistant disease with up to 2 prior lines, and more rigorous eligibility criteria.

RESULTS:

CRLX101 was well tolerated other than nausea, fatigue and anemia. 29 pts. received a median of 3 (1-16) cycles with a clinical benefit rate (CBR) of 68% and overall response rate (ORR) of 11%. With the addition of Bev in Cohort B (n = 34), the CBR was increased to 95% and the ORR to 18%. PFS was 4.5 months (0.9 to 15.9 months) in Cohort A and 6.5 months (2.8 to 14.4 months) in Cohort B. Bev increased the incidence of hypertension and qualitatively increased bladder toxicities, but without SAEs.

CONCLUSIONS:

CRLX101 meets the clinical need for an effective and tolerable topoisomerase I inhibitor and can be safely combined with bevacizumab.

• Authors: Carolyn N Krasner, Susana M Campos, Chantay L Young, Karan R Chadda, Hang Lee, Michael J Birrer, Neil S Horowitz, Panagiotis A Konstantinopoulos, Antonella M D'Ascanio, Ursula A Matulonis, Richard T Penson
• Journal: Gynecologic oncology (Gynecol Oncol) Vol. 162 Issue 3 Pg. 661-666 (09 2021) ISSN: 1095-6859 [Electronic] United States
• PMID: 34243976 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021. Published by Elsevier Inc.

Chemical References

• Cyclodextrins
• IT-101
• Bevacizumab
• Camptothecin

Topics

• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Bevacizumab (administration & dosage, adverse effects)
• Camptothecin (administration & dosage, adverse effects, therapeutic use)
• Carcinoma, Ovarian Epithelial (drug therapy)
• Cyclodextrins (administration & dosage, adverse effects, therapeutic use)
• Female
• Humans
• Middle Aged
• Neoplasm Recurrence, Local (drug therapy)
• Ovarian Neoplasms (drug therapy)
• Peritoneal Neoplasms (drug therapy)