A Study of TTI-622 in Combination With Daratumumab Hyaluronidase-fihj in People With Multiple Myeloma

NCT05139225 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: 21-122
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 7

Brief Summary

This study will test the safety of TTI-622 in combination with daratumumab hyaluronidase-fihj in people with relapsed/refractory multiple myeloma. The researchers look for the highest dose TTI-622 that causes few or mild side effects in participants when given in combination with daratumumab hyaluronidase-fihj. Once the researchers find the highest safe dose of each study drug, they will further test the combination TTI-622 + daratumumab hyaluronidase-fihj) in new participants to find out if the combinations are effective in treating relapsed/refractory multiple myeloma. Researchers think that combining TTI-621 or TTI-622 with daratumumab hyaluronidase-fihj, a standard treatment for multiple myeloma, may be an effective treatment approach.

Conditions

Multiple Myeloma

Keywords

TTI-622; Daratumumab Hyaluronidase-fihj; 21-122

Outcome Measures

Primary Outcomes (1)

• Incidence of dose-limiting toxicities

  Dose limiting toxicities are defined as any of the following treatment emergent adverse events that occur during the 28-day DLT observation period, inclusive of pre-dose testing on C2D1. Adverse events for which a relationship to study treatment cannot be ruled out should be considered possibly related to treatment. Toxicity grading will be adjudicated according to NCI CTCAE version 5.

  28-day observation period following C1D1 of therapy

Secondary Outcomes (2)

• Overall response of TTI-621

  2 years

• Overall response of TTI-622

  2 years

Study Arms (2)

TTI-622 dosing will occur over 8 weeks + Daratumumab Hyaluronidase-fihj

EXPERIMENTAL

TTI-622 will be administered weekly at the assigned dose levels per the ramp-up schedule. Daratumumab hyaluronidase-fihj 1800 mg will administered on a standard schedule consisting of weekly administration for 8 weeks, every other week administration for 16 weeks, followed by every 4-week administration thereafter.

Drug: TTI-622; Drug: Daratumumab Hyaluronidase-fihj

TTI-622 dosing will occur over 4 weeks + Daratumumab Hyaluronidase-fihj

EXPERIMENTAL

TTI-622 will be administered weekly at the assigned dose levels per the ramp-up schedule. Daratumumab hyaluronidase-fihj 1800 mg will administered on a standard schedule consisting of weekly administration for 8 weeks, every other week administration for 16 weeks, followed by every 4-week administration thereafter.

Drug: TTI-622; Drug: Daratumumab Hyaluronidase-fihj

Interventions

TTI-622 DRUG

(-2) 0.4 mg/kg (-1) 0.8 mg/kg (1 ) 1.2 mg/kg (2) 2 mg/kg (3) 4 mg/kg (4) 8 mg/kg (5) 12 mg/kg The appropriate dose of TTI-622 will be administered IV over 60 minutes, however, can be extended up to 4 hours to mitigate Infusion-related reactions.

TTI-622 dosing will occur over 4 weeks + Daratumumab Hyaluronidase-fihj; TTI-622 dosing will occur over 8 weeks + Daratumumab Hyaluronidase-fihj

Daratumumab Hyaluronidase-fihj DRUG

Daratumumab hyaluronidase-fihj SC 1800 mg days 1, 8, 15, and 22.

TTI-622 dosing will occur over 4 weeks + Daratumumab Hyaluronidase-fihj; TTI-622 dosing will occur over 8 weeks + Daratumumab Hyaluronidase-fihj

Eligibility Criteria

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

You may qualify if:

• Patients with relapsed or refractory multiple myeloma, as defined by the international myeloma working group (IMWG) updated criteria (Appendix A) who have measurable disease defined by one or more of the following:
• Serum myeloma (M)-protein greater than or equal to 0.5 g/dL (5 g/L).
• Urine M-protein greater or equal to 200 mg/24 h.
• Involved light chain (either kappa or lambda) is \>10 mg/dL with an abnormal kappa: lambda ratio.
• A biopsy proven plasmacytoma(s) that is new or definitely increased. Increase is defined as a 50% and at least 1 cm increase as measured serially by the sum of the products of the cross-diameters of the measurable lesion.
• Patients must have received at least 3 prior lines of therapy not having received Daratumumab Hyaluronidase-fihj in the last line of therapy, and have been previously exposed to a proteasome inhibitor, an IMiD and be considered refractory to an FD Aapproved anti-CD38 mAb used either in combination or as a single agent. Refractory is defined as progression on or within 60 days of receiving a treatment program containing an anti-CD38 monoclonal antibody.
• Female or male patients age ≥18 years.
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-2. PS-3 is permitted if PS is due solely to bone pain.
• Adequate hematological function including:
• Absolute neutrophil count (ANC) \>1,000/mm\^3 (unless myelosuppression is secondary to bone marrow plasmacytosis expressed by \>50% of cellularity).
• Platelet count \>75,000/mm\^3 for the dose finding portion, and \> 50,000/ mm\^3 for the expansion part.(transfusion is not permitted within 7 days of enrollment)
• Hemoglobin ≥8.0 g/dL (transfusion support is not permitted within 7 days of enrollment).
• Adequate Renal Function defined by:
• a. Estimated creatinine clearance \>30 mL/min as calculated using the CKD-EPI equation. (If an estimated creatinine clearance CrCl is believed to be inaccurate for a patient, 24-hour urine collection with actual assessment of CrCl is allowed)
• Adequate Liver Function, including:

You may not qualify if:

• Patients with other malignancies in addition to multiple myeloma are not eligible if the other malignancy has required treatment within the past 3 years or is not in complete remission with the exceptions of successfully treated non-metastatic basal cell carcinoma, squamous cell skin carcinoma, or in-situ carcinoma.
• History of active autoimmune disorders (including but not limited to: Crohn's disease, rheumatoid arthritis, scleroderma, systemic lupus erythematosus, Grave's disease) and other conditions that require systemic therapy, which may compromise or impair the immune system.
• Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease).
• Patients with active uncontrolled bacterial, fungal or viral infection, including known human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS) related illness.
• Major surgery within 4 weeks prior to study entry.
• Radiation therapy within 2 weeks prior to study entry (bone lesions requiring radiation may be treated with limited \[i.e., ≤ 25% of bone marrow in field\] radiation therapy during this period).
• Patients with a history of stem cell transplant (autologous or allogeneic) within 100 days prior to study enrollment.
• Donor Lymphocyte Infusion (DLI) within 30 days prior to study entry.
• Therapy with a monoclonal antibody, including but not limited to antiCD38 antibody, elotuzumab, T or NK cell re-directing therapy (ex. bispecific therapy), or antibody-drug conjugate within 30 days of study treatment initiation. Treatment with other anti-multiple myeloma therapies within 14 days of study treatment initiation.
• Patient known to be refractory to platelet or red blood cell transfusions.
• Any of the following in the previous 6 months: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure (CHF, New York Heart Association Class III or IV), cerebrovascular accident, transient ischemic attack or symptomatic pulmonary embolism.
• Fertile male patients and female patients of childbearing potential who are unwilling or unable to use a highly effective method of contraception as outlined in this protocol for the duration of the study and for at least 28 days after the last dose of investigational product.
• Other acute or chronic medical or psychiatric condition, including recent (within the past year) or active suicidal ideation or behavior or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Trillium Therapeutics Inc.: collaborator

Study Sites (7)

Memorial Sloan Kettering Cancer Center

Basking Ridge, New Jersey, 07920, United States

Location

Memorial Sloan Kettering Monmouth

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering Bergen

Montvale, New Jersey, 07645, United States

Location

Memorial Sloan Kettering Commack

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Westchester

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Nassau

Uniondale, New York, 11553, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Multiple Myeloma

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Alexander Lesokhin, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: A standard 3+3 dose escalation design.

Study Record Dates

• First Submitted: October 28, 2021
• First Posted: December 1, 2021
• Study Start: October 28, 2021
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2026
• Last Updated: November 4, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share

Locations

US (7)