Leronlimab in Combination With Regorafenib in Patients With CCR5+, Metastatic Colorectal Cancer

NCT05730673 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: CD08_mCRC
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is aPhase II Study of Leronlimab (PRO 140) in combination with Regorafenib in Patients with CCR5+, Microsatellite Stable (MSS), Metastatic Colorectal Cancer (mCRC)

Conditions

CCR5; Microsatellite Stable; Metastatic; Colorectal Cancer

Keywords

Metastatic; Colorectal Cancer

Outcome Measures

Primary Outcomes (1)

• Overall response rate (ORR, defined as Complete Response (CR) + Partial Response (PR)) in subjects with CCR5+ mCRC treated with Leronlimab (PRO 140) and Regorafenib.

  Four weeks

Secondary Outcomes (5)

• The number, frequency, and severity of adverse events (AEs) collected from the time of first treatment until 12 weeks after study treatment completion to evaluate safety of Leronlimab (PRO 140) and Regorafenib in subjects with CCR5+ mCRC.

  Four weeks

• Progression free survival (PFS) defined as time in months from the date of first study treatment to the date of disease progression or death from any cause, whichever comes first.

  Four weeks

• Overall survival defined as time in months from the date of first study treatment to the date of death;

  Four weeks

• Time to new metastases (TTNM)

  Four weeks

• The change from baseline in circulating tumor cells (CTC) in the peripheral blood.

  Four weeks

Other Outcomes (1)

• Measure serum level of CCL2, CCL3, CCL4 and CCL5 and correlate with therapeutic benefit (PFS) in patient with mCRC.

  Four weeks

Study Arms (1)

Leronlimab in combinatiob with Regorafenib

EXPERIMENTAL

Leronlimab (PRO 140) will be administered subcutaneously at a weekly dose of 700 mg in combination with staring dose of 80 mg Regorafenib at first week of the Cycle 1, followed by escalation of Regorafenib dose to 120 mg and 160 mg in second and third weeks of Cycle 1, respectively. No Regorafenib will be administered during the fourth week.

Drug: 700mg leronlimab weekly dose; Drug: 80mg Regorafenib at week 1; Drug: 120mg Regorafenib at week2; Drug: 160 mg Regorafenib at week 3

Interventions

700mg leronlimab weekly dose DRUG

leronlimab is a humanized IgG4,κ monoclonal antibody (mAb) to the chemokine receptor CCR5

Leronlimab in combinatiob with Regorafenib

80mg Regorafenib at week 1 DRUG

Regorafenib is a small-molecule multiple kinase inhibitor

Leronlimab in combinatiob with Regorafenib

120mg Regorafenib at week2 DRUG

Regorafenib is a small-molecule multiple kinase inhibitor

Leronlimab in combinatiob with Regorafenib

160 mg Regorafenib at week 3 DRUG

Regorafenib is a small-molecule multiple kinase inhibitor

Leronlimab in combinatiob with Regorafenib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patient age ≥ 18 years with a history of treated colorectal cancer with unresectable metastases of the primary colorectal cancer to the other organs.
• Demonstrate CCR5 + by IHC (\>10% membranous staining completed at the reference laboratory of Dr. Hallgeir Rui at Medical College of Wisconsin).
• Note: This test will be done as part of the pre-screening period. It will be performed in archival metastatic tissue.
• Histologically confirmed for microsatellite stable MSS colorectal cancer by Immunohistochemistry (IHC) or Next-generation sequencing (NGS)
• Metastatic colorectal cancer (CRC) who have been previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, VEGF antibody, and, if RAS wild-type, an anti-EGFR therapy Note: Prior Regorafenib therapy is not allowed.
• Have measurable disease per RECIST 1.1
• Have provided archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated.
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Expected survival of at least three months
• No chemotherapy treatment within the last four weeks or less than wash out period of the chemotherapy agents, whichever is shorter
• Patients must have adequate organ and bone marrow function within 28 days prior to registration, as defined below:
• Leukocytes ≥ 3,000/mcL;
• Absolute neutrophil count ≥ 1,500/mcL;
• Platelet count \> 75,000/mm\^3
• Total bilirubin: within normal institutional limits;

You may not qualify if:

• Inability to understand the aims of the study and/or protocol procedures
• Hypersensitivity towards Regorafenib or Leronlimab (PRO 140).
• History of severe allergic, anaphylactic, or other hypersensitivity reactions to humanized monoclonal antibodies
• Any other concurrent antineoplastic treatment including irradiation (local radiation of single non-target lesions for palliation only allowed)
• Any condition requiring continuous systemic treatment with either corticosteroids (\>10 mg daily prednisone equivalents) or other immunosuppressive medications within 2 weeks prior to first dose of study treatment. Inhaled or topical steroids and physiological replacement doses of up to 10 mg daily prednisone equivalent are permitted in the absence of active autoimmune disease.
• Clinically significant active coronary heart disease and cardiovascular insufficiency with hypotension (systolic blood pressure \<100 mmHg) per PI discretion.
• Cardiac arrhythmias requiring anti-arrhythmic therapy; Note: pace makers, beta blockers, or digoxin are permitted
• Any GI or Respiratory system disorders that per PI discretion can interfere with the study treatment or jeopardize the patient's health.
• Prior allogeneic bone marrow transplantation
• Administration of a live, attenuated vaccine within four weeks prior to start of maintenance treatment or anticipation that such a live attenuated vaccine will be required during the remainder of the study Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.
• Positive test for human immunodeficiency virus (HIV) or HIV infection
• Active hepatitis B (defined as having a positive hepatitis B surface antigen \[HBsAg\] test) or hepatitis C. Note: Patients with past hepatitis B virus (HBV) infection or resolved HBV infection (defined as having a negative HBsAg test and a positive antibody to hepatitis B core antigen antibody test) are eligible.
• Active or latent tuberculosis
• Clinically active brain metastases, defined as untreated symptomatic, or requiring therapy with steroids or anticonvulsants to control associated symptoms.
• Patient who have an active infection requiring systemic therapy.

Sponsors & Collaborators

• CytoDyn, Inc.: lead
• Amarex Clinical Research: collaborator

MeSH Terms

Conditions

Neoplasm Metastasis; Colorectal Neoplasms

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 7, 2023
• First Posted: February 16, 2023
• Study Start: September 20, 2022
• Primary Completion: May 27, 2023
• Study Completion: August 10, 2023
• Last Updated: February 17, 2023

Record last verified: 2023-02