Date: 2015-06-01
Type of information: Presentation of results at a congress
phase: 1b-2
Announcement: presentation of results at the American Society of Clinical Oncology (ASCO) annual meeting, in Chicago
Company: Cerulean Pharma (USA - MA)
Product: CRLX101 - poly-CD-PEG-camptothecin
Action
mechanism: enzyme inhibitor/topoisomerase inhibitor. CRLX101 is a dynamically tumor-targeted nanoparticle-drug conjugate (NDC) designed to concentrate in tumors and slowly release its anti-cancer payload, camptothecin, inside tumor cells. CRLX101 inhibits topoisomerase 1 (topo 1), which is involved in cellular replication, and hypoxia-inducible factor-1α (HIF-1α), which research suggests is a master regulator of cancer cell survival mechanisms thought to promote drug and radiation resistance. CRLX101 has shown activity in four tumor types in late stage disease and in a front line setting, and it has shown activity as monotherapy and in combination with other cancer treatments. CRLX101 is currently in Phase 2 clinical development and has been dosed in more than 250 patients.
Disease: relapsed renal cell carcinoma
Therapeutic area: Cancer - Oncology
Country:
Trial details:
Latest
news: * On June 1, 2015, Cerulean Pharma announced that full data from a Phase 1b/2 investigator-sponsored trial of CRLX101 in combination with Avastin® (bevacizumab) in metastatic renal cell carcinoma, or RCC, was presented at the 2015 American Society of Clinical Oncology Annual Meeting, or ASCO. In addition, three CRLX101 trials in progress posters were presented at ASCO describing a randomized Phase 2 trial of CRLX101 in combination with Avastin in patients with 3rd and 4th line RCC, a Phase 2 trial of CRLX101 in combination with Avastin in patients with 2nd and 3rd line platinum-resistant ovarian cancer, and a Phase 1b/2 trial of CRLX101 in combination with chemoradiotherapy, or CRT, in the neoadjuvant treatment of newly diagnosed rectal cancer. Highlights from the ASCO posters include: - Phase 1b/2 trial evaluating CRLX101 in combination with Avastin in treatment-refractory metastatic renal cell carcinoma - Presented by Principal Investigator, Stephen Keefe, M.D., Abramson Cancer Center, University of Pennsylvania Phase 1b/2 investigator-sponsored trial, or IST, being conducted at two U.S. cancer centers in patients with metastatic RCC 2nd through 6th line patients (n=22) Primary endpoint (50% of patients achieving ≥ 4 months progression free survival, or PFS) met with 12/22 patients achieving ≥ 4 months PFS Median PFS observed among all patients was 9.9 months including: 11.21 months among 2nd line patients (n=4), 7.59 months among 3rd through 6th line patients (n=18) Overall response rate, or ORR, observed among all patients was 23% including: 1 partial response (PR) in 2nd line patients (25% ORR), 4 PRs in 3rd through 6th line patients (22% ORR), 3 PRs among patients with clear cell histology, 2 PRs among patients with non-clear cell histology - Randomized Phase 2 trial evaluating CRLX101 in combination with Avastin in 3rd and 4th line RCC versus standard of care - Presented by Principal Investigator, Martin Voss, M.D., Memorial Sloan Kettering Cancer Center Randomized Phase 2 clinical trial being conducted at 38 U.S. and 5 South Korean cancer centers in patients with advanced, unresectable metastatic RCC who have completed 2 or 3 prior regimens of therapy Phase 2 IST being conducted at three U.S. cancer centers in patients with platinum resistant ovarian cancer who have received 1 or 2 prior regimens of chemotherapy. Primary endpoint is rate of PFS at 6 months. Secondary endpoints are ORR and assessment of toxicity - Phase 1b/2 trial evaluating CRLX101 in combination with CRT in neoadjuvant treatment of newly diagnosed rectal cancer -Presented by Principal Investigator, Andrew Wang, M.D., Lineberger Comprehensive Cancer Center, University of North Carolina-Chapel Hill Phase 1b/2 IST being conducted at six U.S. cancer centers in patients with non-metastatic rectal cancer who have received no prior therapy. Objectives of this trial include: Define the rate of pathologic complete response, or pCR, among patients receiving CRLX101 in combination with CRT, Characterize the safety and toxicity profile of this combination, Estimate disease-free survival, or DFS, and overall survival, or OS, Explore changes in HIF-1α and other plasma biomarkers, Explore the association between baseline tumor biomarkers and pCR. * On December 15, 2014, Cerulean Pharma announced completion of enrollment of 22 patients in a Phase 1b/2 clinical proof of principle trial of its lead nanoparticle-drug conjugate, CRLX101, in combination with Avastin® in relapsed renal cell carcinoma (RCC). This study is an investigator-sponsored trial (IST) being conducted by the University of Pennsylvania and Thomas Jefferson University Hospital with support from Cerulean. The Principal Investigator is Dr. Stephen Keefe of the University of Pennsylvania Abramson Cancer Center. Data previously presented from the first 11 patients from this study showed a 27% response rate (three RECIST responses) in a setting where standard of care historically provides only a 2-4% response rate. A 7.6 months median progression-free (PFS) survival was observed, which is double the roughly 3.5 months PFS achieved by standard-of-care in this setting. Based on these data, Cerulean launched a company-sponsored randomized Phase 2 trial of CRLX101 in combination with Avastin in 3rd and 4th line RCC in August 2014, which is currently ongoing.
Average durability of response was 3.5 months from PR to time off study
Consistent with Phase 1 results presented at ASCO 2014, combination of CRLX101 and Avastin continues to be generally well tolerated with no dose limiting toxicities observed
As of May 2015, two patients remain active on study in cycles 8 and 11 respectively. Final data from this trial will be submitted for publication in a peer-reviewed journal later this year. Cerulean is enrolling a randomized Phase 2 clinical trial of CRLX101 in combination with Avastin in 3rd and 4th line RCC patients.
Primary endpoint will compare PFS among 90 clear cell RCC patients treated with concurrently administered CRLX101 plus Avastin versus investigator's choice of standard of care
Primary endpoint will employ a blinded independent radiographic review in order to ensure clinical trial integrity
Statistical power is set at 80% to detect an increase in mPFS from 3.5 months to 5.8 months with a hazard ratio of 0.6
Secondary/exploratory endpoints include overall survival, ORR, safety, pharmacokinetics, and plasma biomarkers
20 patients with non-clear cell RCC histology will be evaluated independently
Enrollment of 110 patients is ongoing and is expected to be complete by Autumn 2015
- Phase 2 trial evaluating CRLX101 in combination with Avastin in recurrent platinum-resistant ovarian cancer - Presented by Principal Investigator, Carolyn Krasner, M.D., Massachusetts General Hospital, Harvard Medical School
