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

About

Brief Summary

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.

Primary Purpose

Treatment

Study Type

Interventional

Phase

Phase 2

Eligibility

Gender

All

Healthy Volunteers

No

Minimum Age

18 Years

Maximum Age

N/A

Inclusion Criteria:

Must be at least 18 years of age.
An ECOG performance status of ≤ 2.
Life expectancy of ≥ 4 months.
Able to eat and digest food normally. Patients with colostomies are allowed.
Must meet the following:
- 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.
- Determined by the Investigator to be ready to receive their second dose of chemotherapy.
- 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.
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.
Must be able and willing to safely self-inject daily or be injected by a caregiver.
Must have evaluable disease by RECIST 1.1.
Must have adequate end organ function as defined by:
- ANC ≥ 1.5 × 10^9/L
- 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
- 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
- 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
- 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
- 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
- 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
- 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
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
If a female of childbearing capability, must have a negative pregnancy test within 2 weeks of starting treatment.
Fertile men and women must agree to use adequate contraception for the duration of the trial.
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

Patients receiving second line or later systemic treatment
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.
History of weight loss surgery including gastric stapling, or bypass surgery.
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.
Chronic and ongoing use of corticosteroids at a dose of ≥5 mg of prednisone or equivalent per day.
History of bulimia or anorexia.
Pregnancy, lactation, or plans to become pregnant.
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.
Concurrent participation in any other clinical trial.
Patients with known brain or CNS metastases.
Impaired cardiac function or significant cardiac issues including, but not limited to, any of the following:
- Greater than class II NYHA congestive heart failure
- Congenital long QT syndrome
- QTc > 470 msec (as calculated by institution standards) confirmed by two ECGs ≥ 1-minute apart (QTc interval corrected using [Fridericia's formula [QTcF])
- Unstable angina pectoris
- Acute myocardial infarction ≤ 6 months prior to study entry
Known hypersensitivity to mifomelatide or its formulation.
History of allergic or anaphylactic reaction to any chemotherapeutics.
Known diagnosis of HIV infection (HIV testing is not mandatory). Patients with a history of HIV regardless of viral load are excluded.
Active infection with Hepatitis B, Hepatitis C, or active systemic viral disease or active severe infection.
Unwilling or unable to comply with the protocol.
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

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Study Stats

Protocol No.

25-0996