Date: 2015-10-23
Type of information: Presentation of results at a congress
phase: 1-2
Announcement: presentation of results at the European Society of Gynaecological Oncology (ESGO) International Meeting in Nice
Company: Aprea (Sweden)
Product: APR-246 in combination with carboplatin and pegylated doxorubicin
Action
mechanism: Cancers develop and spread due to the malfunction of the cells’ normal growth control mechanisms. One of the best-known cancer genes is p53 that can trigger the cellular suicide program to eliminate cancer cells. In about half of all tumors, p53 is mutated and no longer functions normally. This allows cancer cell survival and rapid tumor growth. Aprea has successfully developed substances that can restore normal function to the p53 protein and thereby induce efficient cancer cell death and overcome resistance to antitumoral therapy. To the company’s knowledge, APR-246 is the only compound with this mechanism of action in clinical development.
Disease: ovarian cancer
Therapeutic area: Cancer - Oncology - Rare diseases
Country: Belgium, UK
Trial
details: The Phase I/II trial is designed to evaluate the safety, efficacy, pharmacokinetics and pharmacodynamics of APR-246 in combination with carboplatin (AUC 5) and pegylated doxorubicin (30 mg/m2), a second line standard of care chemotherapy for relapsed platinum sensitive high grade serous ovarian cancer. The Phase I/II trial is a two-part study that will enroll approximately 180 patients. Part A is an open-label, multiple ascending dose study. The primary objectives of Part A are to evaluate the safety and tolerability of APR-246 in combination with carboplatin and pegylated doxorubicin, and to confirm the dose of APR-246. Pending successful completion of this phase, Aprea expects to initiate Part B of the trial, which will be a randomized, controlled study investigating the safety and antitumor activity of APR-246 administered in combination with carboplatin and pegylated doxorubicin, compared with carboplatin and pegylated doxorubicin alone. Primary end point of part B will be Progression Free Survival (PFS). (NCT02098343)
Latest
news: * On October 23, 2015, Aprea AB, a Karolinska Development AB (Nasdaq Stockholm: KDEV) portfolio company, announces updated preliminary data from its ongoing Phase Ib/II clinical study in collaboration with The European Network for Translational Research in Ovarian Cancer (EUTROC). The data will be presented on Saturday, October 24, at the European Society of Gynaecological Oncology (ESGO) International Meeting in Nice, France and reinforces the indicative conclusions presented from the study on April 20, 2015; that APR-246 can be combined with standard of care chemotherapy and that preliminary efficacy data of the combination regimen show activity in treatment of recurrent ovarian cancer ( a Phase Ib Study Combining APR-246 with Standard Chemotherapy in Platinum Sensitive Relapsed High Grade Serous Ovarian Carcinoma (HGSOC). * On April 16, 2014, Aprea announced that dosing has begun in the Phase I/II proof-of-concept clinical trial of APR-246 in combination with chemotherapy in patients with relapsed platinum sensitive high grade serous ovarian cancer. “The synergistic effects of APR-246 and carboplatin have resulted in very potent antitumor activity in preclinical models. We now look forward to evaluate the compound’s safety profile and clinical activity in combination treatment of ovarian cancer patients”, said Ulf Björklund, CEO at Aprea.
Preliminary results for the first 24 patients in the Phase Ib part of the study are announced of which 8 patients have completed all 6 cycles of combination therapy with APR-246. At cut-off, all patients treated in the study have stable disease or better according to RECIST criteria. In addition, 13 out of 14 evaluable patients have GCIG CA-125 (tumor antigen biomarker) response after 3 treatment cycles. Hence the preliminary efficacy data indicate that APR-246 in combination with chemotherapy has activity in patients with partially platinum sensitive as well as patients with platinum sensitive disease.
APR-246 showed linear pharmacokinetics with no accumulation and low intra patient variability and no indication of interaction between APR-246 and chemotherapy was seen. This indicates that APR-246 can be combined with carboplatin and doxorubicin at relevant doses.
No new safety concerns have emerged in the study. The main treatment-emergent adverse events have been low grade gastrointestinal and central nervous system related events. One dose limiting toxicity (DLT) of ruptured diverticulum occurred at the second dose level leading to expansion of this cohort to 6 patients. A possible increase in hematological side effects over those expected with the chemotherapy alone cannot be ruled out at this stage.
APR-246 has previously been tested in a clinical Phase I/II trial in 32 patients with refractory hematological malignancies or prostate carcinoma. Promising data from this trial has been presented in Journal of Clinical Oncology.
