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:

  • 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.

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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

 

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

 cabazitaxel-jevtana-efficacy

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

 cabazitaxel-jevtana-safety

Interim Results Announcement

  

DEP® cabazitaxel case study in prostate cancer

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Last Update: 30 November 2021

 

Other DEP® cabazitaxel case studies

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Last Update: 24 June 2021

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 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).

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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® 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. 

Related Announcements

 

Other Announcements

 

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

 


 

^ 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.