405 POSTER Final results of a Phase I/II study of CTCE-9908, a novel anticancer agent that inhibits CXCR4, in patients with advanced solid cancers

A153 Introduction: CTCE-9908 is a 17 amino acid peptide CXCR4 antagonist that has been shown to block the interaction of the CXCR4 receptor with CXCL12 (SDF-1), critical in the infiltration of organ tissues by metastatic cells. CXCR4 receptors are expressed on many malignant cell types. SDF-1, the CXCR4 ligand is produced in large amounts by organs representing the first sites of metastasis for many malignant cell types. Recently, CXCR4 has also been shown to play a role in angiogenesis. CTCE-9908 is expected to be effective against a wide range of cancer types that express CXCR4 by inhibiting the metastatic process. This phase I/II study was designed to determine the maximal tolerated dose (MTD), toxicity profile, pharmacokinetics and antitumor activity of CTCE-9908 in patients (pts) with refractory late-stage solid tumors. Patients and Methods: The agent was administered over 30 minutes, intravenously daily during weekdays for 20 doses in escalating doses to eligible pts using an accelerated titration design. Five dose levels (DLs) from 0.25mg/kg to 5.0mg/kg were planned. Twenty-two pts have been entered in 5 cohorts: DL 1 (0.25) - 2 pts; DL 2 (0.5) - 1 pt; DL 3 (1.0) - 4 pts; DL 4 (2.5) - 2 pts; DL 5 (5) - 13 pts. Twenty-one pts received study drug since one pt at DL1 progressed prior to starting treatment. DL 5 was expanded to obtain more information on toxicity and efficacy specific to pts with ovarian, breast, prostate and ‘other’ CXCR4-expressing cancers. Pts with stable disease (SD) or better after cycle 1 were eligible to receive further cycles. For 21 evaluable pts, median age was 56 years (range, 30-84), 62% were female. Primary tumor types: breast (6 pts), ovary (4 pts), lung (3 pts), melanoma (2 pts), others (6 pts). Results: Adverse event (AE) data are available for the first 21 pts. No pt had DLT. Most common drug-related toxicity consisted of grade 2 phlebitis (3pts), grade 2 gingivitis (2 pts) and grade 3 GGT elevation (1 pt). Of 20 pts assessable for response: PD (10), SD (5), N/A (5). Of the pts with SD after first cycle, 3 had ovarian cancer, 2 had breast cancer and 1 had small bowel cancer. Seven pts entered the continuation phase after cycle 1. One pt with small bowel cancer has now completed 4 cycles of therapy. One pt with ovarian cancer had a decrease in CA-125 from 657 to 303 after 1 cycle with a decrease in baseline target lesions but was found to have a brain metastasis not evaluated on screening, presumably from a concurrent breast cancer. Conclusions: CTCE-9908, an anticancer agent with a novel mechanism of action, is well tolerated and has shown preliminary signs of efficacy, especially in ovarian cancer. A phase II study is planned in that population. The expansion phase of the current trial continues and should complete accrual shortly.