Safely Optimizing Body Weight With Mifomelatide (TCMCB07) in Patients With Newly Diagnosed Colorectal Cancer (CRC) or Pancreatic Ductal Adenocarcinoma (PDAC) Undergoing Chemotherapy

This is a randomized, double-blind, placebo-controlled basket trial evaluating mifomelatide (TCMCB07) administered daily by subcutaneous (SC) injection in up to 120 patients. Patients will be enrolled into two cohorts 1) patients with newly diagnosed, advanced, unresectable colorectal cancer (CRC) or 2) patients with newly diagnosed, advanced, unresectable pancreatic ductal adenocarcinoma (PDAC). Within each cohort, patients will be randomized 1:1:1:1 to receive placebo or one of three different doses of mifomelatide (12.5 mg, 25 mg, or 50 mg). This study is designed to evaluate the effects of different doses of mifomelatide on weight, body composition and BMI. The double-blind (DB) phase will generally begin on the first day of the second cycle of first-line cancer chemotherapy and continue for 12-weeks with the goal of maintaining body weight and muscle mass in patients undergoing chemotherapy relative to control. Upon completion of the DB treatment period, eligible patients may enroll in an optional Open Label Extension (OLE) phase and receive mifomelatide SC 25 mg daily for up to an additional 26 weeks. The purpose of the OLE is to further evaluate long-term safety, tolerability and efficacy of mifomelatide.

Study Overview

• Status: Recruiting
• Conditions: Cancer Weight Loss
• Intervention / Treatment: Drug: Placebo; Drug: TCMCB07

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Daniel Marks, MD/PHD; Phone Number: 503-754-5624; Email: dan@endevicabio.com
• Study Contact Backup: Name: Meghan Joly, PhD; Email: Meghan@endevicabio.com

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Recruiting
      • Cross Cancer Institute
      • Contact: Michael Sawyer, MD
• United States
  • Arizona
    • Tucson, Arizona, United States, 85715
      • Recruiting
      • Arizona Clinical Research Center
      • Contact: Manuel Modiano, MD
  • California
    • Los Angeles, California, United States, 90048
      • Recruiting
      • Cedars-Sinai Medical Center
      • Contact: Jun Gong, MD
    • Santa Monica, California, United States, 90404
      • Recruiting
      • UCLA Medical Center
      • Contact: Jingran Ji, MD
  • Florida
    • Coral Springs, Florida, United States, 33071
      • Recruiting
      • Life Clinical Trials
      • Contact: Sumit Sawhney, MD
    • Hialeah, Florida, United States, 33013
      • Recruiting
      • Bioresearch Partners
      • Contact: Luis Rangel, MD
    • Margate, Florida, United States, 33063
      • Recruiting
      • D&H Cancer Research Center
      • Contact: Emilio Araujo-Mino, MD
    • Miami Beach, Florida, United States, 33140
      • Recruiting
      • Mt. Sinai Cancer Center
    • Tamarac, Florida, United States, 33321
      • Recruiting
      • BRCR Global
      • Contact: Chintan Gandhi, MD
  • Georgia
    • Atlanta, Georgia, United States, 30318
      • Recruiting
      • Piedmont Healthcare Inc.
      • Contact: Eyal Meiri, MD
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Not yet recruiting
      • Northwestern University - Robert H. Lurie Comprehensive Cancer Center
      • Contact: Ishan Roy, MD, PhD
    • Hinsdale, Illinois, United States, 60521
      • Not yet recruiting
      • Hope and Healing Cancer Services
      • Contact: Srilata Gundala, MD
    • Skokie, Illinois, United States, 60077
      • Recruiting
      • Orchard Healthcare Research
      • Contact: Ira Oliff, MD
  • Kansas
    • Wichita, Kansas, United States, 67214
      • Recruiting
      • Cancer Centers of Kansas
      • Contact: Shaker Dakhil, MD
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Recruiting
      • Karmanos Cancer Center
      • Contact: Wasif Saif, MD
  • Nebraska
    • Lincoln, Nebraska, United States, 68506
      • Recruiting
      • NHO Revive Research Institute
      • Contact: Kailash Mosalpuria, MD
    • Omaha, Nebraska, United States, 68130
      • Recruiting
      • Nebraska Cancer Specialists
      • Contact: Joel Michalski, MD, PhD
  • New York
    • New York, New York, United States, 10016
      • Recruiting
      • NYU Langone Health Perlmutter Cancer Center
      • Contact: Paul Oberstein, MD
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Recruiting
      • Duke University Medical Center
      • Contact: Aman Opneja, MBBS
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73102
      • Recruiting
      • Hightower Clinical
      • Contact: Sanjaykumar Hapani, MD
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Not yet recruiting
      • Medical University of South Carolina
      • Contact: Denis Guttridge, PhD
  • Tennessee
    • Memphis, Tennessee, United States, 38120
      • Recruiting
      • Baptist Clinical Research
      • Contact: Donald Gravenor, MD
    • Nashville, Tennessee, United States, 37232
      • Not yet recruiting
      • Vanderbilt-Ingram Cancer Center
      • Contact: Rajiv Agarwal, MD
  • Texas
    • Kingwood, Texas, United States, 77090
      • Recruiting
      • LUMI Research
      • Contact: David Nguyen, MD
    • Laredo, Texas, United States, 78041
      • Recruiting
      • Laguna Clinical Research Associates
      • Contact: Eduardo Miranda, MD
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • Recruiting
      • University of Virginia
      • Contact: Matthew Reilley, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Must be at least 18 years of age.
2. An ECOG performance status of ≤ 2.
3. Life expectancy of ≥ 4 months.
4. Able to eat and digest food normally. Patients with colostomies are allowed.

5. Must meet the following:

   1. Newly diagnosed colorectal adenocarcinoma (CRC) or pancreatic ductal adenocarcinoma (PDAC) that is unresectable, locally advanced (i.e., surgery with curative intent is not an option) or metastatic. Note: patients must not have relapsed within 6 months after completing prior treatment for early-stage disease.
   2. Determined by the Investigator to be ready to receive their second dose of chemotherapy.
   3. Patients currently enrolled and receiving study intervention under Protocol Version 2.0 may be eligible to enroll into Protocol Version 3.0, provided the amended protocol has received all regulatory and ethics approvals and the patient has reviewed and signed the updated consent form prior to any procedures conducted under the amended protocol. Enrollment into the OLE phase must occur ≤14 days following completion of the Week 12 DB visit.

6. Patients must be initiating treatment with one of the following chemotherapy regimens:

   a) Gemcitabine plus nab-paclitaxel (GNP), Gemcitabine plus capecitabine, NALIRIFOX, FOLFOX, FOLFIRI, or FOLFIRINOX are permitted. These regimens may be administered with or without bevacizumab, other FDA-approved monoclonal antibodies, or other FDA approved agents as clinically indicated for the patient's cancer type. The primary cancer therapy (including dose, schedule, or specific agents) may be modified as medically indicated.

7. Must be able and willing to safely self-inject daily or be injected by a caregiver.
8. Must have evaluable disease by RECIST 1.1.

9. Must have adequate end organ function as defined by:

   1. ANC ≥ 1.5 × 10^9/L
   2. Platelets ≥ 100 × 10^9/L, or adequate as determined by the medical judgement of the investigator; lab may be repeated as needed to rule out initial transient lab abnormality that does not require medical intervention
   3. Hemoglobin ≥ 9 g/dL, or adequate as determined by the medical judgement of the investigator; lab may be repeated as needed to rule out initial transient lab abnormality that does not require medical intervention
   4. AST and ALT ≤ 3 × ULN; if liver metastases, then ≤ 5 ×ULN; lab may be repeated as needed to rule out initial transient lab abnormality that does not require medical intervention
   5. Bilirubin ≤ 1.5 × ULN or ≤ 3 × ULN in the presence of documented Gilbert's Syndrome; lab may be repeated as needed to rule out initial transient lab abnormality that does not require medical intervention
   6. Albumin between 3.4 and 5.4 gm/dL or within institutional normal limits, or not considered clinically significant by the investigator; lab may be repeated as needed to rule out initial transient lab abnormality that does not require medical intervention
   7. Creatinine clearance ≥ 50 mL/min (calculated by Cockcroft and Gault equation; lab may be repeated as needed to rule out initial transient lab abnormality that does not require medical intervention
   8. Normal hemoglobin A1c levels based on institutional normal limits, or not considered clinically significant by the investigator; lab may be repeated as needed to rule out initial transient lab abnormality that does not require medical intervention
10. NT-Pro-BNP and Troponin (TnI or TnT) are within normal limits or not considered to be clinically significant by the investigator; lab may be repeated as needed to rule out initial transient lab abnormality that does not require medical intervention
11. If a female of childbearing capability, must have a negative pregnancy test within 2 weeks of starting treatment.
12. Fertile men and women must agree to use adequate contraception for the duration of the trial.
13. Willing and able to sign informed consent.

14. Additional cohort-specific inclusion criteria:

    1. CRC Cohort i. Must have a BMI ≤ 29 kg/m^2.
    2. PDAC Cohort i. Cachexia defined by Fearon Criteria of weight loss ii. Patients with diagnosed exocrine pancreatic insufficiency (EPI) must be receiving prescription pancreatic enzyme replacement therapy (PERT) per standard of care (SOC).

Exclusion Criteria

1. Patients receiving second line or later systemic treatment
2. Patients with swallowing abnormalities, malabsorption syndromes, short or inflammatory bowel syndromes, or other conditions that in the Investigator's opinion could impair food consumption or metabolism.
3. History of weight loss surgery including gastric stapling, or bypass surgery.

4. Currently using any new agent prescribed to increase appetite or otherwise affect weight (increase or decrease).

   a) Antiemetics or other standard of care medications for treatment or prevention of nausea and vomiting are acceptable.

   • Patients with newly prescribed glucocorticoids for less than four weeks at the time of Screening and whose weight is not yet stable are excluded. Stable (dose unchanged for 4 weeks or more) and low dose (<5 mg) corticosteroids are permissible, as are inhaled corticosteroids.
   • Drugs like Olanzapine are allowed only when used as an antiemetic, as needed (PRN). If used to treat cachexia, drugs like Olanzapine are not allowed.
5. Chronic and ongoing use of corticosteroids at a dose of ≥5 mg of prednisone or equivalent per day.
6. History of bulimia or anorexia.
7. Pregnancy, lactation, or plans to become pregnant.
8. History of another malignancy except basal cell carcinoma of the skin, carcinoma in situ of the cervix, or other noninvasive or indolent malignancy that has previously undergone potentially curative therapy.
9. Concurrent participation in any other clinical trial.
10. Patients with known brain or CNS metastases.

11. Impaired cardiac function or significant cardiac issues including, but not limited to, any of the following:

    1. Greater than class II NYHA congestive heart failure
    2. Congenital long QT syndrome
    3. QTc > 470 msec (as calculated by institution standards) confirmed by two ECGs ≥ 1-minute apart (QTc interval corrected using [Fridericia's formula [QTcF])
    4. Unstable angina pectoris
    5. Acute myocardial infarction ≤ 6 months prior to study entry
12. Known hypersensitivity to mifomelatide or its formulation.
13. History of allergic or anaphylactic reaction to any chemotherapeutics.
14. Known diagnosis of HIV infection (HIV testing is not mandatory). Patients with a history of HIV regardless of viral load are excluded.
15. Active infection with Hepatitis B, Hepatitis C, or active systemic viral disease or active severe infection.
16. Unwilling or unable to comply with the protocol.
17. Any condition that, in the Investigator's opinion, would impair the patients' ability to participate in this study.

18. Additional cohort-specific exclusion criteria

    1. CRC cohort i. Unintentional weight loss ≥ 10% of usual body weight in 4 months prior to Screening
    2. PDAC cohort i. Neuroendocrine (carcinoid, islet cell) of acing pancreatic carcinoma ii. Unintentional weight loss ≥ 20% of usual body weight in 4 months prior to Screening

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo administered subcutaneously daily for 12 weeks	Drug: Placebo; Matching placebo
Experimental: Mifomelatide (TCMCB07) 12.5 mg administered subcutaneously daily for 12 weeks	Drug: TCMCB07; TCMCB07 is will be provided in single-use vials for subcutaneous administration
Experimental: Mifomelatide (TCMCB07) 25 mg administered subcutaneously daily for 12 weeks	Drug: TCMCB07; TCMCB07 is will be provided in single-use vials for subcutaneous administration
Experimental: Mifomelatide (TCMCB07) 50 mg administered subcutaneously daily for 12 weeks	Drug: TCMCB07; TCMCB07 is will be provided in single-use vials for subcutaneous administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in body weight	At 12 weeks of treatment
Incidence of abnormalities in laboratory evaluations	From enrollment to the end of the 12 week dosing period
Incidence of abnormalities in vital signs	From enrollment to the end of the 12 week dosing period
Incidence and severity of adverse events (AEs), AESIs, and SAEs	From enrollment to the end of the 12 week dosing period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in total score of Functional Assessment of Anorexia/Cachexia Therapy-anorexia-related symptoms scale (FAACT-5IASS)	FAACT-5IASS scores items using a 5-point scale (0-4).Higher scores are associated with a higher health-related quality of life.	At 12 weeks of treatment
Change from baseline in the anorexia and cachexia subscore of the Functional Assessment of Anorexia-Cachexia Therapy (FAACT-ACS) questionnaire	FAACT-ACS score sums 12 items; both use a 5-point scale (0-4).Higher scores are associated with a higher health-related quality of life.	At 12 weeks of treatment
Change from baseline in BMI	Weight and height will be combined to report BMI in kg/m^2	At 12 weeks of treatment
Change from baseline in body weight		At 8 weeks of treatment
Change from baseline in BMI	Weight and height will be combined to report BMI in kg/m^2	At 8 weeks of treatment
Change from baseline in body weight		At 4 weeks of treatment
Change from baseline in BMI	Weight and height will be combined to report BMI in kg/m^2	At 4 weeks of treatment
Change from baseline in the FAACT questionnaire comprising the general quality of life FAACT-G and FAACT-ACS anorexia and cachexia related subscale	FAACTG and FAACT ACS score score items using a 5-point scale (0-4).Higher scores are associated with a higher health-related quality of life.	At 12 weeks of treatment
Change from baseline in total score and subscores of European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30)	Scoring ranges from 0 to 100 with 0 being the worst possible score and 100 being the best.	At 12 weeks of treatment

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in lean mass	Determined by medical imaging	From enrollment to the end of the 12 week treatment period
Change from baseline in fat mass	Determined by medical imaging	From enrollment to the end of the 12 week treatment period
Change from baseline in tumor burden	To determine the response rate by RECIST 1.1 criteria	At 12 weeks of treatment
Blood levels of mifomelatide	Plasma concentrations of mifomelatide collected at prespecified sampling timepoints	From enrollment to the end of the 12 week treatment period
Immunogenicity profile of mifomelatide		From enrollment to the end of the 12 week treatment period
Effect of mifomelatide on chemotherapy relative dose intensity	Comparison of actual dose intensity ratio versus expected chemotherapy dose intensity ratio between mifomelatide and placebo groups	From enrollment to the end of 12 week treatment period
Effect of mifomelatide on time-to-deterioration (TTD) in body weight	Time from first dose of study treatment to first clinically meaningful worsening from baseline appetite score (defined as a 4-point decrease in FAACT-ACS score).	From enrollment to the end of 12 week treatment period
Effect of mifomelatide on overall survival at predefined timepoints including Week 12 in the DB and 6 and 9 months in the OLE	Landmark overall survival rates, defined as the proportion of patients alive at each specified timepoint (Week 12, Month 6 and Month 9) following the first dose of study intervention.	From enrollment to the end of 12 week treatment period, Month 6 and Month 9 in OLE
Characterize disease progression outcomes in study patients	Progression-free survival (PFS), defined as the time from first documentation of disease progression or death from any cause, whichever occurs first (including OLE where applicable).	From enrollment through Week 26 in OLE where applicable
Overall survival	Overall survival (OS), defined as the time from first dose of study drug in the DB phase to death from any cause (including OLE where applicable).	From enrollment to death from any cause (including OLE where applicable)

Collaborators and Investigators

• Sponsor: Endevica Bio

Study record dates

Study Major Dates

• Study Start (Actual): April 28, 2025
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: March 25, 2025
• First Submitted That Met QC Criteria: April 17, 2025
• First Posted (Actual): April 22, 2025

Study Record Updates

• Last Update Posted (Actual): July 15, 2026
• Last Update Submitted That Met QC Criteria: July 13, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: Weight Loss; Chemotherapy; metastatic pancreatic cancer; Pancreatic cancer; Cachexia; BMI; CRC; Metastatic colorectal cancer; PDAC; colorectal adenocarcinoma; cancer weight loss; advanced, unresectable colorectal cancer; advanced, unresectable PDAC
• Additional Relevant MeSH Terms: Endocrine System Diseases; Neoplasms by Site; Neoplasms; Body Weight; Intestinal Diseases; Body Weight Changes; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Colonic Diseases; Thinness; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Weight Loss; Colorectal Neoplasms; Pancreatic Neoplasms; Cachexia; Substandard Drugs; Pharmaceutical Preparations; Counterfeit Drugs
• Other Study ID Numbers: TCMCB07-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No