TCMCB07 Enters Phase 2 for Weight Loss in Stage IV Colorectal Cancer
Following promising phase 1 data, TCMCB07 is being further evaluated in a phase 2 trial for the treatment of patients with stage IV colorectal cancer.
3D medical illustration of colorectal cancer: © anatomy insider - stock.adobe.com
The first patient with stage IV colorectal cancer has been dosed with TCMCB07 (B07) in a phase 2 trial to prevent weight loss in patients with cancer who are undergoing chemotherapy.1
The trial is being conducted in partnership between Endevica Bio and WuXi Clinical. A total of 100 patients with stage IV metastatic colorectal cancer will be enrolled and treated with TCMCB07 as they begin chemotherapy, as well as during the first several rounds of chemotherapy.
The primary end point of the study is preventing weight loss, which can lead to cachexia, and the study is expected to enroll patients across 20 sites.
"This marks an important milestone in our commitment in developing a potentially life-changing treatment for cachexia," said Russell Potterfield, chief executive officer and executive chair of Endevica, in a press release. "Each trial brings us closer to offering a viable solution for this debilitating disease, and we remain dedicated to making a lasting impact on the lives of those affected."
TCMCB07, a melanocortin‐3/4 antagonist peptide candidate, is currently being developed for the treatment of cachexia. The potential first-in-class peptide drug has the ability to cross the blood-brain barrier and act on target receptors that previously were inaccessible to modulate the body's behavioral and metabolic response to chronic illness.
Preclinically, TCMCB07 has demonstrated significant lean muscle mass retention during its administration. A phase 1 clinical trial (NCT05529849) also evaluated TCMCB07 and was completed in 2024. In the study, TCMCB07 showed strong safety and efficacy, including improved appetite and preserved lean mass and fat mass. TCMCB07 also showed potential to alleviate chemotherapy-induced anorexia and weight loss for patients with cancer.
In the phase 1 study, a single-center, double-blind, randomized, sequential assessment of 5 single ascending dose cohorts and 3 multiple ascending dose cohorts of TCMCB07, patients were treated with subcutaneous TCMCB07 or placebo each day for 5 consecutive days.2 A total of 40 patients completed the single ascending dose and 36 patients completed the multiple ascending dose portions of the trial.
The study’s primary end points were safety and tolerability, and the secondary end point was characterization of pharmacokinetics (PK).
According to the preliminary analysis of the results, no patients had abnormal vital signs, abnormal electrocardiograms, or drug-related serious adverse events (AEs). The most frequently seen study-related AEs were injection site reactions, which were grades 1 or 2.
For PK, initial pharmacokinetic data revealed a higher-than-predicted Cmax and area under the curve in humans compared with preclinical findings. Consequently, the dose in cohort 3 was reduced to ensure the Cmax did not exceed that observed in cohort 5 of the single ascending dose portion of the study.
In the multiple ascending dose portion, a statistically significant difference in weight change from baseline to the end of study was observed between the placebo and active treatment arms within cohorts 2 and 3 (1.07 kg; P =.0195). Patients receiving TCMCB07 in these cohorts reported a 15% greater ease in eating, as measured by a visual analog scale for hunger, compared with the placebo group. This difference reached statistical significance at one time point (P =.0497) but not at another (P =.0892).
These findings support further investigation of TCMCB07's potential in mitigating cancer-related cachexia in the ongoing, randomized, phase 2 clinical trial.
"We are incredibly excited to have our first patient dosed with B07 in individuals diagnosed with metastatic colorectal cancer who are undergoing chemotherapy," said Daniel Marks, MD, PhD, chief medical and scientific officer of Endevica Bio, in a press release.1 "Since there is no FDA approved therapeutic for cancer cachexia, this trial is a crucial step to provide a therapy for an area of huge unmet clinical need, and we look forward to the results."
