CAP-100 for Subjects With Relapsed/Refractory Chronic Lymphocytic Leukemia

• ClinicalTrials.gov Identifier: NCT04704323
• Recruitment Status: Recruiting
• First Posted: January 11, 2021
• Last Update Posted: September 15, 2022
• Sponsor: Catapult Therapeutics
• Information provided by (Responsible Party): Catapult Therapeutics

Study Description

Brief Summary:

Introduction of immuno-chemotherapy in the treatment options of CLL and SLL changed the treatment paradigm of these diseases. Presently, first-line therapies for CLL/SLL include targeted therapies (e.g. ibrutinib, acalabrutinib) or combined immuno-chemotherapy regimens (e.g., fludarabine, cyclophosphamide, and rituximab for patients aged <65 years without del17p/TP53 mutations or bendamustine and rituximab for patients ≥65 years who have additional comorbidities).

Despite the gradual introduction of targeted therapies, new treatment strategies efficacious for patients ineligible for/unresponsive to these therapies are still required. These new strategies should ideally overcome disease relapse and circumvent compound-specific safety challenges. Emerging treatment options include new compounds aimed for both untreated and relapsed/refractory CLL, and combination therapies of existing compounds that extend single-agent efficacy in specific high-risk patient populations.

CAP-100 is expected to prevent the migration of leukemia cells to and their survival in lymphoid niches as well as to eliminate CCR7-positive leukemia cells via ADCC, resulting in measurable clinical responses.

The present trial is the first-in-human trial of CAP-100 and is divided into two phases. The aim of the Phase Ia (dose escalation) is to define the Recommended Phase 2 Dose (RP2D) versus the Maximum Tolerated Dose (MTD) of CAP-100 in subjects with CLL.

Phase Ib of the trial (expansion phase) will evaluate the safety and preliminary clinical benefit of CAP-100 monotherapy at RP2D (response rate, lymph node size reduction, assessment of minimal residual disease [MRD]) to support the design of future trials investigating CAP-100 either as monotherapy or in a combination setting with approved treatments for CLL.

Condition or disease	Intervention/treatment
Lymphocytic Leukemia, Chronic; SLL	Drug: CAP-100

Study Design

• Study Type: Observational
• Estimated Enrollment: 25 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: An Open Label Phase Ia/b Dose Escalation Followed by Dose Expansion Safety and Tolerability Trial of CAP-100, a Humanized C-C-chemokine Receptor 7 Antibody, Administered as Monotherapy in Subjects With r/r Chronic Lymphocytic Leukemia
• Actual Study Start Date: September 10, 2021
• Estimated Primary Completion Date: September 2023
• Estimated Study Completion Date: September 2023

Groups and Cohorts

Group/Cohort	Intervention/treatment
Experimental: Phase Ia - Dose escalation; Cohorts of 3 subjects will receive intravenous [IV] administrations of escalating doses of CAP-100.	Drug: CAP-100; CAP-100 (humanized antibody against C-C-chemokine receptor 7 [CCR]7)
Experimental: Phase Ib - Dose expansion; Six subjects will receive intravenous [IV] administrations of CAP-100 at the Recommended Phase 2 Dose determined in Phase Ia - Dose Escalation of this trial.	Drug: CAP-100; CAP-100 (humanized antibody against C-C-chemokine receptor 7 [CCR]7)

Outcome Measures

Primary Outcome Measures :

1. Incidence of treatment emergent adverse effects at increasing doses of CAP-100 (safety and tolerability) [ Time Frame: 28 Days ]

   The incidence of Grade 3 and Grade 4 AEs related to CAP-100 administration according to the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 for non-hematological AEs.

   The incidence and severity of hematological AEs related to CAP-100 treatment according to CLL international working group criteria (iwCLL, Hallek et al, 2018).

2. Incidence of treatment emergent adverse effects of CAP-100 at RP2D in an expanded cohort (safety and tolerability) [ Time Frame: 28 Days ]

   The incidence of Grade 3 and Grade 4 AEs related to CAP-100 administration according to the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 for non-hematological AEs.

   The incidence and severity of hematological AEs related to CAP-100 treatment according to CLL international working group criteria (iwCLL, Hallek et al, 2018).

3. Preliminary clinical benefit of CAP-100 monotherapy at RP2D [ Time Frame: 3 Cycles (84 Days) ]
   Overall response rate (ORR) after 3 cycles of CAP-100 treatment according to iwCLL criteria

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

The target population is subjects relapsed or refractory to at least two prior standard systemic treatment regimens for CLL or SLL and having no available therapies known to provide clinical benefit.

Criteria

Inclusion Criteria:

1. Age ≥ 18 years.
2. Able to understand and sign a written informed consent document.
3. Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2.
4. Relapsed or refractory to at least two (2) prior standard systemic treatment regimen for CLL or SLL and without available therapies known to provide clinical benefit.
5. Prior CLL or SLL systemic therapy must have been discontinued for a duration of at least five times its half-life (palliative low dose steroids are allowed to bridge the time to CAP-100; major surgery or irradiation for CLL must have been completed > 4 weeks prior to the first trial dose of medication). Prior chimeric antigen receptor (CAR)-T cell therapy is allowed.
6. Life expectancy > 16 weeks.
7. Subjects must have met the diagnostic criteria for CLL according to the iwCLL 2018 guidelines (Hallek et al, 2018) or for SLL (NCCN guidelines, 2020) at some point during their disease course.
8. Subjects must meet iwCLL 2018 guideline criteria (Hallek et al, 2018) for active disease.
9. Platelet count ≥ 50,000/ μL, unless decrease is attributable to bone marrow infiltration of CLL.
10. Adequate liver function as indicated by aspartate transaminase (AST)/ alanine transaminase (ALT) ≤ 2.5 times upper limit of normal (ULN), unless directly attributable to the subject's tumor (in this case, acceptable levels are ≤ 5 x ULN).
11. Renal function as defined by creatinine clearance (CrCl)≥ 45 mL/min/1.73m2 (by CKD-EPI formula).
12. Women of childbearing potential and male subjects who have partners capable of reproduction must agree to use an effective contraceptive method during the course of the trial and for 4 months following the completion of their last treatment. Women of childbearing potential must have a negative serum β-subunit of hCG gonadotropin (β-hCG) pregnancy test result within 7 days of first trial dose. Female subjects who are surgically sterilized or who are > 45 years old and have not experienced menses for > 2 years may have β-hCG pregnancy test waived.

Exclusion Criteria:

1. Allogeneic stem-cell transplantation within 6 months of trial entry.
2. Monoclonal antibody for anti-cancer therapy within 4 weeks of trial entry.
3. Side effects due to prior therapy not recovered to ≤Grade 1.
4. Oral targeted inhibitors (Bruton's tyrosine kinase [BTK]-inhibitors, B-cell lymphoma 2 [BCL-2] inhibitors, phosphoinositide 3-kinase [PI3K] inhibitors) within five times their half-life.
5. Active viral, bacterial or systemic fungal infection requiring treatment.
6. Subjects who are known to be human immunodeficiency virus (HIV)-positive.
7. Subjects with active known central nervous system (CNS) lymphoma.
8. Pregnant or lactating women.
9. History of previous cancer < 2 years before the trial, except controlled disease using systemic therapy with curative intent, surgical therapy with curative intent or skin cancer, cancer in situ, and prostate cancer on the "watch and wait" approach.
10. Uncontrolled intercurrent illness including, but not limited to, New York Heart Association Class (NYHA) III and IV congestive heart failure, myocardial infraction within the previous 6 months, ejection fraction (EF) < 40%, life-threatening arrhythmias, or unstable angina brain metastasis or psychiatric illness that would limit compliance with trial requirement.
11. Subjects with known hypersensitivity to any excipient contained in the drug formulation.
12. Subjects with a history of documented human anti-globulin antibodies.
13. Active autoimmune disease, motor neuropathy considered of autoimmune origin, and other CNS autoimmune disease.

Contacts and Locations

Contacts

Contact: Dominik Höchli, MD; +31 611846572; d.hochli@catapult-therapeutics.com

Locations

United States, Massachusetts

Dana-Farber Cancer Institute; Recruiting

Boston, Massachusetts, United States, 02215

Contact: Sobana Balasubramanian 857-215-1681 SobanaJ_Balasubramanian@DFCI.HARVARD.EDU

Principal Investigator: Jennifer Brown

United States, North Carolina

Duke University; Recruiting

Durham, North Carolina, United States, 27705

Contact: Terri Lucas 919-681-6580 terri.lucas@duke.edu

Principal Investigator: Danielle Brander, MD

Sub-Investigator: Andrea Sitlinger, MD

United States, Ohio

Ohio State University; Active, not recruiting

Columbus, Ohio, United States, 43210

Spain

Hospital Universitario de La Princesa; Not yet recruiting

Madrid, Spain, 28006

Contact: Carmen Montes 34915202316 cm.jimenez.hematologia@gmail.co

Principal Investigator: Javier Loscertales

Hospital Universitario de Santiago de Compostela; Not yet recruiting

Madrid, Spain, 28040

Contact: Beatriz Antelo Beatriz.Antelo.Rodriguez@sergas.es

Principal Investigator: Adrián Mosqueira

Hospital Universitario Marqués de Valdecilla; Not yet recruiting

Santander, Spain, 39008

Contact: Alba del Rio Manzano 34 942315275 amanzano@idival.org

Principal Investigator: Lucrecia Yáñez San Segundo

Sponsors and Collaborators

Catapult Therapeutics

More Information

Publications:

Hallek M, Cheson BD, Catovsky D, Caligaris-Cappio F, Dighiero G, Dohner H, Hillmen P, Keating M, Montserrat E, Chiorazzi N, Stilgenbauer S, Rai KR, Byrd JC, Eichhorst B, O'Brien S, Robak T, Seymour JF, Kipps TJ. iwCLL guidelines for diagnosis, indications for treatment, response assessment, and supportive management of CLL. Blood. 2018 Jun 21;131(25):2745-2760. doi: 10.1182/blood-2017-09-806398. Epub 2018 Mar 14.

• Responsible Party: Catapult Therapeutics
• ClinicalTrials.gov Identifier: NCT04704323
• Other Study ID Numbers: CAP-100-1
• First Posted: January 11, 2021
• Last Update Posted: September 15, 2022
• Last Verified: September 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, B-Cell; Chronic Disease; Disease Attributes; Pathologic Processes