Trial to Evaluate Antibody-Drug Conjugate in Treating Metastatic Colorectal Cancer

THE TOPLINE

  • Early results from a Phase I trial indicate that the antibody-drug conjugate IMMU-130 is safe and tolerable in treating relapsed metastatic colorectal cancers
  • Investigators believe IMMU-130 may be more potent than the traditional treatment, as it binds directly to cancer cells

Fox Chase medical oncologist Efrat Dotan, MD, is spearheading a Phase I clinical trial of IMMU-130, an antibody-drug conjugate, studying its efficacy and safety for use against metastatic colorectal cancers (mCRC) that have relapsed.

“This is a novel treatment approach using an antibody-drug conjugate to deliver the treatment directly into the cancer cell and limit toxicity to healthy tissue,” says Dotan.

The main cancer-fighting component of the treatment is SN-38. Known as a topoisomerase inhibitor, SN-38 interferes with tumor cell replication, eventually leading to the death of those cells. Although long used in treating mCRC, the drug is normally delivered in the form of irinotecan, which requires processing by the patient’s liver to become metabolically active as SN-38. Despite this, the liver usually converts less than five percent of the drug to its active form. Conjugating SN-38 itself to another compound that binds specifically with cancer cells means that physicians can deliver a much more potent, targeted, and reduced dose of the drug, which they hope will be effective even for patients whose cancers relapsed after a chemotherapy regimen based on more traditional irinotecan treatment.

Efrat Dotan, MD

Efrat Dotan, MD

IMMU-130 is an immune conjugate in which SN-38 is attached to an anti-CEACAM5 antibody. CEACAM5, a carcinoembryonic antigen, is highly expressed on the surface of cancer cells in general and colorectal cancer cells in particular. Many colorectal tumors express high levels of CEACAM5, which makes it a prime candidate for targeting chemotherapy drugs to tumor cells without harming non-cancerous tissue.

The primary objective of the study is to evaluate the safety and tolerability of IMMU-130 and to determine the maximum tolerated dose among patients with mCRC who have been treated previously with at least one prior irinotecan-containing regimen. Accrual to the trial closed in December 2014, and so far Dotan and colleagues have observed good tolerability for the drug among study participants. Early signs of activity with this agent were seen with a few durable long-term responses.

“Our initial experience with this agent has been exciting, with manageable toxicity and some responses even in patients with irinotecan refractory disease,” says Dotan.

The researchers presented their preliminary results at the American Society of Clinical Oncology’s 2014 Annual Meeting.

Above, scans show tumor shrinkage in a relapsed mCRC patient treated with IMMU-130, who achieved a total tumor shrinkage of 87.5% while in the study.

Above, scans show tumor shrinkage in a relapsed mCRC patient treated with IMMU-130, who achieved a total tumor shrinkage of 87.5% while in the study.