DEP® irinotecan (Phase 2)

DEP® irinotecan is an improved version of irinotecan (Camptosar®), predominantly used for colorectal cancer.

DEP® irinotecan is a novel, patented nanoparticle formulation of SN-38, the active metabolite of irinotecan, delivered using Starpharma’s proprietary DEP® technology.

Irinotecan (Camptosar®) is a major cancer drug used to treat colorectal cancer with peak global sales of >US$1.1 billion despite having multiple US FDA “Black Box” warnings. Irinotecan is a pro-drug that requires conversion to its active metabolite, SN38. The need for this conversion may lead to variable clinical effect/efficacy and toxicity among patients.

DEP® solubilises SN38 and allows direct dosing, avoiding the need for liver conversion. DEP® irinotecan has been shown to demonstrate improved efficacy in multiple animal models and has patent filings to 2039 (plus up to an additional ~5 years).

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Download DEP® Drug Delivery Summary (pdf file, 1007kb).

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DEP® irinotecan clinical status

DEP® irinotecan phase 2 program is currently underway. The program is an open-label trial, with the objective of establishing anti-tumour activity (efficacy) and safety at the Recommended Phase 2 Dose (RP2D).

Encouraging efficacy signals have been observed in trial patients for multiple tumour types, including colorectal, ovarian, breast, pancreatic, lung and oesophageal cancer. The DEP® irinotecan phase 2 program has received enthusiastic support from clinicians due to limited treatment options for colorectal cancer. Starpharma is exploring commercially relevant value-adding combinations for DEP® irinotecan, including with immuno-oncology (IO) agents.

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DEP® irinotecan case studies

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 Last Update: 24 June 2021

 

DEP® irinotecan phase 1 results

  • 7 patients were enrolled and received DEP® irinotecan at a range of doses up to 12.5 mg/m2 and up to 10 cycles of treatment each
  • Encouraging efficacy signals observed in 50% of evaluable patients to date, and in all three tumour types enrolled, despite the fact conventional irinotecan is not approved for breast or pancreatic cancers & that enrolled patients were heavily pre-treated.
  • Efficacy signals observed included prolonged stable disease and substantial tumour shrinkage in a range of tumour types including CRC, pancreatic and breast cancer.
  • Patients generally experienced less severe side effects than typically associated with Camptosar®, with no cases of the severe high-grade diarrhoea which is experienced by 20-40% of patients with conventional irinotecan and often requires hospitalisation
  • Conventional irinotecan (Camptosar®) has two FDA black box warnings (severe diarrhoea and neutropenia) and is associated with a high frequency of adverse events, including nausea, vomiting, alopecia and neutropenia
  • Adverse events observed with DEP® irinotecan treatment were consistent with those seen in Camptosar® but generally less severe and mostly mild (grade 1)
  • Adverse events observed with DEP® irinotecan included nausea, vomiting, alopecia and neutropenia

(Evaluable patients are those patients who have received ≥1 dose DEP® irinotecan and have had a tumour assessment conducted post treatment)

Full Results Announcement

 

DEP® irinotecan preclinical results

DEP® irinotecan in combination with immuno-oncology agent boosts efficacy and survival in multiple colon cancer models.

DEP® irinotecan in combination with an immuno-oncology (IO) agent (anti PD-1 antibody) showed superior anti-tumour activity and significant survival benefit in two colorectal cancer (CRC) preclinical models when compared to the anti PD-1 antibody alone. These results included improvement in both survival and efficacy in the particularly aggressive CT-26 CRC model.

The median survival for the combination of DEP® irinotecan + IO agent (anti PD-1 antibody) was 40 days compared with 13 days for the IO agent alone (refer to the study results below). The enhanced combination benefit seen with DEP® irinotecan was not seen with conventional irinotecan + the same IO agent.

Study Results

Significant enhancement of anti PD-1 antibody (anti PD-1 Ab) activity by DEP® irinotecan in both CT-26 and MC-38 colon cancer models (Figure 1 and 2).

Anti PD-1 antibody alone had minimal impact on this CT-26 model, but efficacy was greatly enhanced when combined with DEP® irinotecan in both the CT-26 (Figure 1) and MC-38 (Figure 2) models. The CT-26 model is recognised as being a highly aggressive CRC model, therefore this result is particularly impressive.

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Figure 1:  Mean tumour volumes over time as measured in the mouse allograft study using CT-26 murine colorectal cancer cells (n=5). DEP® irinotecan + anti PD-1 Ab in combination had a statistically significant greater anti-tumour effect than anti PD-1 Ab alone (p=0.0002) and DEP® irinotecan alone (p=0.0146).

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Figure 2:  Mean tumour volumes over time as measured in the mouse allograft study using MC-38 murine CRC cells (n=5). DEP® irinotecan + anti PD-1 Ab combination had a statistically significant greater anti-tumour effect compared with anti PD-1 Ab alone (p=0.0001).

Full Results Announcement

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DEP® posters showcased at AACR 2020 Annual Meeting

DEP® irinotecan 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. 

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