DEP® cabazitaxel (Phase 2)
DEP® cabazitaxel is an enhanced version of leading prostate cancer drug cabazitaxel (Jevtana®).
Cabazitaxel (Jevtana®) had global sales of €536M in 2020 despite having multiple US FDA “Black Box” warnings.
The advantages* of DEP® cabazitaxel include:
DEP® cabazitaxel has patent filings to 2039 (plus up to an additional ~5 years).
*Multiple preclinical studies have established improved efficacy, survival, and safety with DEP® with many different drugs.
Download DEP® Drug Delivery Summary (pdf file, 1007kb).
DEP® cabazitaxel clinical status
DEP® cabazitaxel phase 2 program is well advanced. The program is an open-label trial, with the objective of establishing anti-tumour activity (efficacy) & safety.
Encouraging efficacy signals have been observed, including radiological responses, significant target tumour shrinkage and substantial tumour biomarker reductions (e.g. Prostate Specific Antigen - PSA), in cancers including prostate, ovarian, lung, gastroesophageal, head and neck, and other cancers.
- Positive DEP® phase 2 interim results in prostate cancer
- DEP® cabazitaxel progresses to phase 2 on positive results
- Promising efficacy signals observed in ongoing DEP® trials, including DEP® cabazitaxel escalation phase
DEP® cabazitaxel phase 2 - Positive interim results in prostate cancer cohort
DEP® cabazitaxel – phase 2 prostate cancer patients
- 25 heavily pre-treated patients (average age 73 years) with Stage (IV) hormone-refractory prostate cancer
- Average of 4 prior anti-cancer treatments and >70 cycles/months
- >95% had received prior taxanes, including docetaxel and cabazitaxel (Jevtana®)
- Patients received DEP® cabazitaxel at a dose of 20mg/m2 cabazitaxel
- No need for prophylactic steroids or antihistamines as polysorbate 80-free aqueous formulation
- No primary G-CSF4 prophylaxis required
DEP® cabazitaxel – phase 2 interim results in prostate cancer cohort^
100% of evaluable patients2 had one or more efficacy response3:
- 64% had prolonged disease control for up to 36 weeks
- 18% had significant tumour shrinkage, a Partial Response (Jevtana® – 18.5%)
- 90% had a PSA decrease
- 52% had a ≥50% decrease in PSA (Jevtana® – 29.5%)
- 83% had no progression of secondary bone disease
- 56% evaluable for all three of these measures had responses in all three
Significantly fewer and less severe adverse events reported than for Jevtana:
- Fewer and less severe bone marrow toxicities, particularly neutropenia
- No anaphylaxis observed with DEP® cabazitaxel formulation (aqueous formulation – polysorbate 80-free)
- No severe hypersensitivity or hair loss
- Vast majority of AEs mild to moderate
- Very few patients required G-CSF therapy for myelosuppression
Interim Results Announcement
DEP® cabazitaxel case study in prostate cancer
Last Update: 30 November 2021
Other DEP® cabazitaxel case studies
Last Update: 24 June 2021
DEP® cabazitaxel phase 1 results
- 14 patients enrolled and received DEP® cabazitaxel at doses between 2 mg/m2 to 25 mg/m2
- Up to 15 cycles of DEP® cabazitaxel; no steroid, antihistamine or anti-emetic pre-treatment
- Encouraging signs of efficacy were observed in 67% of patients evaluable for treatment response, including:
- Prolonged stable disease in multiple patients and in a variety of cancer types, including prostate, gastro-oesophageal, breast, ovarian, cholangiocarcinoma and pancreatic (& at doses several-fold lower than usually used for cabazitaxel).
- One prostate cancer patient experienced >47 weeks stable disease & a reduction in Prostate Specific Antigen (PSA) of 79%
- One stage IV ovarian cancer patient achieved a reduction in tumour biomarker
(CA-125) of 56%
- One stage III cholangiocarcinoma cancer patient achieved a 82% decrease in a tumour biomarker after two cycles
- Significantly lower levels of side effects usually associated with Jevtana such as bone marrow toxicity (neutropenia, anaemia, thrombocytopenia), anorexia and vomiting. No cases of hypersensitivity; no cases of hair-loss; no need for anti-nausea medications
(Evaluable patients are those patients who have received ≥1 dose DEP® cabazitaxel and have had a tumour assessment conducted post treatment)
Full Results Announcement
DEP® cabazitaxel preclinical results
Preclinical studies demonstrated that DEP® cabazitaxel achieved significantly superior anti-cancer effects across a range of important cancer types when compared to Jevtana® (standard cabazitaxel).
Figure 1: Antitumour activity of DEP® cabazitaxel as compared to Cabazitacel (Jevtana®) in a human breast cancer xenograft model
Starpharma’s DEP® cabazitaxel was compared with Jevtana® in a human breast cancer preclinical model (xenograft). DEP® cabazitaxel significantly outperformed Jevtana® with respect to both level and duration of tumour regression (anticancer activity). Within four weeks of dosing, 100% of mice treated with Starpharma’s DEP® cabazitaxel were tumour free and remained so for the duration of the extended study (150 days). In contrast, the Jevtana® treated group exhibited significant tumour regrowth from day 60 onwards (Figure 1). Tumour growth in both drug treated groups was significantly inhibited compared with the vehicle group (P<0.0001).1
1Statistical analysis of tumour growth inhibition was performed using ANOVA and Dunnett’s post hoc test.
- DEP® docetaxel and DEP® cabazitaxel outperform in human pancreatic cancer model
- DEP® cabazitaxel shows complete and sustained tumour regression in breast cancer model
- Starpharma's DEP® eliminates cabazitaxel neutropenia
DEP® posters showcased at AACR 2020 Annual Meeting
DEP® cabazitaxel was one of Starpharma's three clinical DEP® products featured in poster presentations at the 2020 Annual American Association for Cancer Research Annual Meeting. These posters showcase preclinical data from Starpharma’s products DEP® docetaxel, DEP® cabazitaxel and DEP® irinotecan, which are all in phase 2 clinical trials. The preclinical data presented at AACR comprises a series of xenograft studies showing enhanced efficacy of DEP® products used as a monotherapy or in combination with standard of care therapies.
- 1715 / 1 - Anti-cancer activity of a SN-38 nanoparticle, DEP® irinotecan, in human colon and pancreatic cancer xenograft models
- 1716 / 2 - Anticancer activity of the taxane nanoparticles, DEP® docetaxel and DEP® cabazitaxel
25 Enrolled participants for DEP® cabazitaxel, 3 patients were not evaluable for efficacy: Jevtana N=598
2: Evaluable patients are those who received ≥1 dose DEP® cabazitaxel and had an applicable efficacy assessment conducted post treatment. 3 patients were not evaluable for efficacy.
3: Scher, H.I., et al., Trial design and objectives for castration-resistant prostate cancer: updated recommendations from the Prostate Cancer Clinical Trials Working Group 3. J Clin Oncol, 2016, 34(12):1402-18
4: G-CSF: granulocyte-colony stimulating factor, is used as a therapy for myelosuppression
# - Partial Response: ≥ 30% reduction in measurable target tumour size
† - Eisenberger, M., et al., Phase III study comparing a reduced dose of cabazitaxel (20 mg/m2) and the currently approved dose (25 mg/m2) in post docetaxel patients with metastatic castration-resistant prostate cancer—PROSELICA. J Clin Oncol, 2017, 35(28):3198-206.