Safely Optimizing Body Weight With TCMCB07 in Patients With Newly Diagnosed Metastatic Colorectal Cancer Undergoing Chemotherapy

Endevica Bio

Status and phase: Enrolling; Phase 2

Conditions: Cancer Weight Loss

Treatments: Drug: TCMCB07; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT06937177

TCMCB07-01

Details and patient eligibility

About

This is a randomized, double-blind, placebo-controlled study of B07, administered daily by subcutaneous (SC) injection, in up to 120 patients with newly diagnosed metastatic colorectal cancer. This study will evaluate different doses of B07 on weight, body composition and BMI in patients with sub-optimal BMIs (≤ 29 kg/m^2). Treatment will start at 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.

Enrollment: 120 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria:

1. Must be at least 18 years of age.

2. An ECOG performance status of ≤ 2.

3. Life expectancy of ≥ 9 months.

4. Able to eat and digest food normally. Patients with colostomies are allowed.

5. Must meet the following:

   1. Newly diagnosed metastatic colorectal adenocarcinoma and about to start first line chemotherapy.
   2. Determined by the Investigator to be ready to receive their second dose of chemotherapy.

6. Starting chemotherapy routines allowed are: FOLFOX, FOLFIRI, or FOLFIRINOX with or without bevacizumab, or other monoclonals or other FDA approved agents to be dosed every 2 weeks. The primary cancer therapy (dose, schedule, or drugs) may be changed as medically indicated.

7. Must have a BMI ≤ 29 kg/m^2.

8. Must be able and willing to safely self-inject daily or be injected by a caregiver.

9. Must have measurable disease by RECIST 1.1 criteria.

10. 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
    3. Hemoglobin ≥ 9 g/dL, or adequate as determined by the medical judgement of the investigator
    4. AST and ALT ≤ 3 × ULN; if liver metastases, then ≤ 5 ×ULN
    5. Bilirubin ≤ 1.5 × ULN or ≤ 3 × ULN in the presence of documented Gilbert's Syndrome
    6. Albumin between 3.4 and 5.4 gm/dL or within institutional normal limits, or not considered clinically significant by the investigator
    7. Creatinine clearance ≥ 50 mL/min (calculated by Cockcroft and Gault equation
    8. Normal hemoglobin A1c levels based on institutional normal limits, or not considered clinically significant by the investigator

11. NT-Pro-BNP and Troponin (TnI or TnT) are within normal limits or not considered to be clinically significant by the investigator.

12. If a female of childbearing capability, must have a negative pregnancy test within 2 weeks of starting treatment.

13. Fertile men and women must agree to use adequate contraception for the duration of the trial.

14. Willing and able to sign informed consent.

Exclusion Criteria

1. Patients receiving second line or later systemic treatment for stage IV disease.

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. Unintentional weight loss ≥ 10% of usual body weight in 4 months prior to Screening or other weight loss considered significant by the Investigator.

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

   1. THC containing agents (e.g., dronabinol, cannabis). Chronic (> 6 months) use is allowed for THC.
   2. Other weight promoting agents including androgenic compounds (e.g., testosterone, oxandrolone), dopamine antagonists, or megestrol acetate within the past 6 months is excluded.
   3. 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 (<4 mg) corticosteroids are permissible, as are inhaled corticosteroids.

6. Chronic and ongoing use of corticosteroids at a dose of ≥5 mg of prednisone or equivalent per day.

7. History of bulimia or anorexia.

8. Pregnancy, lactation, or plans to become pregnant.

9. 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.

10. Concurrent participation in any other clinical trial.

11. Patients with known brain or CNS metastases.

12. 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 (interval corrected using [Bazett's formula [QTcB])
    4. Unstable angina pectoris
    5. Acute myocardial infarction ≤ 6 months prior to study entry

13. Known hypersensitivity to B07 or its formulation.

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

120 participants in 4 patient groups, including a placebo group

Placebo administered subcutaneously daily for 12 weeks

Placebo Comparator group

Treatment:

Drug: Placebo

TCMCB07 12.5 mg administered subcutaneously daily for 12 weeks

Experimental group

Treatment:

Drug: TCMCB07

TCMCB07 25 mg administered subcutaneously daily for 12 weeks

Experimental group

Treatment:

Drug: TCMCB07

TCMCB07 50 mg administered subcutaneously daily for 12 weeks

Experimental group

Treatment:

Drug: TCMCB07