Date: 2016-06-04
Type of
information: Presentation of results at a congress
phase: 1b
Announcement: presentation of results at the American Society of Clinical Oncology (ASCO) annual meeting, in Chicago
Company: Aduro Biotech (USA - CA)
Product: CRS-207
Action
mechanism:
- immunotherapy product/live product. CRS-207 is Aduro’s LADD-based therapeutic that has been engineered to promote the expression of the tumor-associated antigen, mesothelin (which is present in multiple tumor types, including pancreatic cancer). LADD technology is designed to enable the safe administration of Listeria mononcytogenes bacteria by deleting two genes critical to the bacterium’s natural virulence – internalin B and act A, which control infection of hepatocytes and spread of bacterial DNA. The attenuated strain of bacteria is then modified with new genetic material to encode and express specific tumor antigens. The engineered Listeria is designed to be absorbed by the patient’s antigen presenting cells, including dendritic cells, which are primary initiators of both the innate and adaptive immune responses. Once absorbed, the LADD-engineered bacterium releases genetic material and antigens into the dendritic cell cytosol. The dendritic cell immediately launches an innate immune response (by releasing cytokines and other signaling proteins) and then processes the tumor antigen genes from the LADD bacterium. These antigens are presented on the dendritic cell surface where they are “read” by CD4 and CD8 T cells, which then initiate an adaptive immune response specific to the target antigen.
Disease: unresectable malignant pleural mesothelioma
Therapeutic
area: Cancer - Oncology - Rare diseases
Country: USA
Trial
details:
- This clinical trial will evaluate the safety and immune response of the sequential administration cancer vaccine CRS-207 (with or without cyclophosphamide) followed by standard of care chemotherapy (pemetrexed and cisplatin). CRS-207 is a weakened (attenuated) form of Listeria monocytogenes that has been genetically-modified to reduce its capacity to cause disease, while maintaining its ability to stimulate potent immune responses. CRS-207 has been engineered to elicit an immune response against the tumor-associated antigen mesothelin, which has been shown to be present at higher levels on certain tumor cells (such as mesothelioma) than on normal cells. Pemetrexed and cisplatin are the standard chemotherapy regimen to treat malignant pleural mesothelioma. This trial will evaluate whether giving CRS-207 cancer vaccine with chemotherapy will induce anti-tumor immune responses and/or objective tumor response. (NCT01675765)
Latest
news:
- • On June 4, 2016, Aduro Biotech announced the presentation of updated data from an ongoing Phase 1b clinical trial of its immunotherapy product candidate CRS-207 in combination with pemetrexed and cisplatin (standard of care chemotherapy) as front-line treatment for patients with unresectable malignant pleural mesothelioma. The results from the first of two cohorts were presented in a poster presentation at the 2016 American Society of Clinical Oncology Meeting ( ASCO ) held in Chicago . Of the 36 evaluable patients, disease control was observed in 94% (34/36), including 3% (1/36) with a complete response, 56% (20/36) with partial responses and 36% (13/36) experiencing stable disease following treatment with CRS-207 and chemotherapy. Prior to receiving chemotherapy, 31% (11/36) of patients experienced some tumor shrinkage (range: -1% to -43%) after receiving CRS-207 alone. The estimated median overall survival was 16.4 months (95% CI: 11.0 - 20.6 months). CRS-207 was generally well-tolerated with no treatment-related serious adverse events or cumulative toxicities when administered with chemotherapy.
- The multi-center Phase 1b study enrolled chemotherapy-naïve patients with unresectable MPM and good performance status (ECOG 0 or 1) to receive two doses of CRS-207, followed by up to six cycles of chemotherapy and two additional CRS-207 doses. A second cohort of 22 patients is receiving an immunomodulatory dose of cyclophosphamide one day prior to each CRS-207 administration in the same treatment regimen utilized in the first cohort. This cohort is fully enrolled and patient follow-up is ongoing.
- • On September 26, 2015, Aduro Biotech announced the presentation of updated, interim safety and efficacy data from an ongoing Phase 1b clinical trial of its novel immunotherapy, CRS-207, in combination with standard of care chemotherapy in patients with unresectable malignant pleural mesothelioma. Of the 34 evaluable patients, disease control was observed in 94% (32/34), including 59% (20/34) with partial responses and 35% (12/34) experiencing stable disease following treatment with CRS-207 and chemotherapy. Of note, in three patients who had tumor biopsies completed, biomarker analysis data available at the time of the presentation showed in all three patients a consistent and marked recruitment of immune cells, including CD8+ T-cells, dendritic cells and natural killer cells, following treatment with CRS-207. The results were presented by Raffit Hassan, M.D., co-chief of the Thoracic and GI Oncology Branch at the National Cancer Institute, in a spotlight poster presentation (abstract #515/P249) at the 40TH European Society for Medical Oncology (ESMO)/18TH European Cancer Congress (ECC) being held September 25-29, 2015 in Vienna, Austria. At the time of the ESMO presentation, the multi-center Phase 1b study had completed enrollment with 38 patients who were chemotherapy-naïve, with unresectable malignant pleural mesothelioma, good performance status (ECOG 0 or 1) and adequate organ function. Under the trial design, eligible patients received two treatments with CRS-207 two weeks apart, followed by up to six cycles of standard of care pemetrexed and cisplatin chemotherapy three weeks apart and two CRS-207 treatments three weeks apart. Clinically stable patients receive CRS-207 maintenance courses every eight weeks and are followed until disease progression. Objectives of the study are safety, immunogenicity, objective tumor responses and tumor marker kinetics.
- Median duration of response was 5.3 months (95% CI: 4.7 – 16.7 months) and median progression free survival was 8.5 months (95% CI: 6.9 – 10.8 months). No treatment-related serious adverse events or unexpected toxicities were observed. Treatment, follow-up and immune response evaluations are ongoing.
- • On August 10, 2015, Aduro Biotech announced that it has completed enrollment in the Phase 1b clinical trial of its novel immunotherapy, CRS-207, in combination with standard-of-care chemotherapy in patients with unresectable malignant pleural mesothelioma (MPM). The multi-center Phase 1b trial enrolled 38 patients who were chemotherapy-naive, had unresectable MPM, had good performance status (ECOG 0 or 1), and adequate organ function. The company plans to advance directly to a Phase 3 clinical trial with CRS-207 in combination with standard-of-care chemotherapy in patients with unresectable MPM in the first half of 2016. In the Phase 1b trial, eligible patients received two prime vaccinations with CRS-207 two weeks apart, followed by up to six cycles of standard-of-care pemetrexed and cisplatin chemotherapy three weeks apart and two CRS-207 boost vaccinations three weeks apart. Clinically stable patients received CRS-207 maintenance vaccinations every eight weeks and were followed every eight weeks until disease progression. Objectives of the study were safety, immunogenicity, objective tumor responses and tumor marker kinetics. Interim data presented at the 2015 American Society of Clinical Oncology Meeting (ASCO) indicate that the combination of CRS-207 with standard-of-care chemotherapy may elicit strong and durable responses in patients with unresectable MPM (see below). Of the 32 evaluable patients enrolled at the time, disease control was observed in 94% (30/32), including 60% (19/32) with partial responses and 34% (11/32) experiencing stable disease following treatment with CRS-207 and chemotherapy. The study sites will remain open to enroll an additional cohort of patients who will receive low-dose cyclophosphamide with CRS-207 and standard-of-care chemotherapy. Preclinical data indicate this combination may further enhance immune response, tumor-specific efficacy and overall survival.
- • On June 1, 2015, Aduro Biotech announced the presentation of interim safety and efficacy data from an ongoing Phase 1b clinical trial of its novel immunotherapy CRS-207 in combination with standard chemotherapy in patients with unresectable malignant pleural mesothelioma (MPM). Of the 32 evaluable patients, disease control was observed in 94% (30/32), including 60% (19/32) with partial responses and 34% (11/32) experiencing stable disease following treatment with CRS-207 and chemotherapy. The results were presented by Raffit Hassan, M.D., co-chief of the Thoracic and GI Oncology Branch at the National Cancer Institute, in a poster presentation (abstract #7565) at the 2015 American Society of Clinical Oncology Meeting (ASCO) held in Chicago.
- At the time of the ASCO presentation, the multi-center Phase 1b study had enrolled 36 patients who were chemotherapy-naïve, had unresectable MPM, good performance status (ECOG 0 or 1) and adequate organ function. Under the trial design, eligible patients received two prime vaccinations with CRS-207 two weeks apart, followed by up to six cycles of standard of care pemetrexed and cisplatin chemotherapy three weeks apart and two CRS-207 boost vaccinations three weeks apart. Clinically stable patients receive CRS-207 maintenance vaccinations every eight weeks and are followed every eight weeks until disease progression. Objectives of the study are safety, immunogenicity, objective tumor responses and tumor marker kinetics. The median time of treatment was 6.9 months (range: 0.3 – 26.2 months). Median duration of response was 5.0 months (95% CI: 3.7 – 11.5 months) and median progression free survival was 7.4 months (95% CI: 6.9 – 10.8 months). No treatment-related serious adverse events or unexpected toxicities were observed. Treatment, follow-up and immune response evaluations are ongoing.
Is
general: Yes
