DEP® cabazitaxel (Phase 2)

DEP^® cabazitaxel is a dendrimer version of leading prostate cancer drug cabazitaxel.

Cabazitaxel (Jevtana®) had global sales of €536M in 2020 despite having multiple US FDA “Black Box” warnings. The advantages* of DEP® cabazitaxel include: Improved side effect profile Detergent-free formulation No steroid pre-treatment Tumour-targeting Improved efficacy 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.

Related Announcements

• Starpharma presents promising additional clinical data for DEP® cabazitaxel in prostate cancer
• 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

• Starpharma presents promising additional clinical data for DEP® cabazitaxel in prostate cancer
• Positive DEP® phase 2 interim results in prostate cancer

 

DEP^® cabazitaxel phase 1 results

(Dose escalation)

• 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 progresses to phase 2 on positive results

 

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.

Related Announcements

• 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

Related Announcements

• Multiple DEP^® products showcased at AACR 2020

 

Other Announcements

• US patent issued for DEP cabazitaxel nanoparticle

 

Download DEP^® Drug Delivery Summary (pdf file, 1007kb) or Contact Us for further information.

 

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^{^ Starpharma Pty Ltd ASX announcement, 25 Nov 2021}

^{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.}