Intetumumab in treatment of metastatic CRPC


In theory, one would hope that it would be possible to find an appropriate monoclonal antibody that could be used in combination with chemotherapy to treat patients with late stage prostate cancer and that would have significant impact on survival.

A paper by Chu et al., just pre-published online in Investigational New Drugs, reports on a very early (Phase I) clinical trial of  the safety and efficacy of a monocolonal antibody known as intetumumab (pronounced intet-youm’you-mab) in combination with docetaxel in patients with metastatic, castration-resistant prostate cancer (CRPC). Intetumumab is also known as CNTO 95 and is being developed by Johnson & Johnson companies.

This study was a phase I, open-label, multi-center, non-randomized study. The 10 patients enrolled in the study all received a standard dose of docetaxel on day 1 of each of nine 21-day treatment cycles and intetumumab (either 5 or 10 mg/kg) was administered on days 1, 8, and 15 of cycles 2 and 3 and on day 1 of all subsequent cycles. This is a complicated dosing regimen, and although the study abstract does not mention this, we know that patients were also receiving daily dosing with predisone (as reported in the trial protocol).

The primary endpoint in this study was the incidence of dose-limiting toxicities (DLTs) of intetumumab during cycles 2 and 3. The results of the trial showed the following:

  • 3 patients were treated with 5 mg/kg of intetumumab and 7 patients received 10 mg/kg.
  • There were no evident DLTs.
  • The majority of treatment-emergent adverse events (TEAEs) occurred in the patients treated with intetumumab 10 mg/kg, and included neutropenia (in 6/7 patients) and nausea (in 5/7 patients).
  • 4/7 patients treated with intetumumab 10-mg/kg  reported serious TEAEs, and febrile neutropenia was considered probably intetumumab-related.
  • In the patients treated with intetumumab 10-mg/kg:
    • 4/7 patients had a serum PSA response (2 of whom responded within 3 months of treatment)
    • 1/7 patients had a partial tumor response for 11 weeks
    • 0/7 patients had progressive disease at cycle 9.
  • No PSA or tumor responses were observed in the patinets treated with intetumumab 5 mg/kg.

The authors conclude that intetumumab was “generally safe and well tolerated in combination with docetaxel” and that “The efficacy of 10 mg/kg intetumumab in combination with docetaxel appears to warrant further study.”

Whether Johnson & Johnson intends to continue investigations into the potential of intetumumab for the treatment of metastatic CPRP seems uncertain at this time. There are no further prostate cancer-specific trials with this drug currently listed on ClincialTrials.gov.

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