Safety, PK and Efficacy of QXL138AM in Patients With Solid Tumors and Multiple Myeloma

Last updated: August 29, 2024
Sponsor: Nammi Therapeutics Inc
Overall Status: Active - Recruiting

Phase

1

Condition

Multiple Myeloma

Lung Cancer

Ovarian Cancer

Treatment

QXL138AM Injection every 2 weeks by IV Infusion

Clinical Study ID

NCT06582017
QXL138AM-001
  • Ages > 18
  • All Genders

Study Summary

Study QXL138AM-001 is a Phase 1a/1b study to investigate the safety, pharmacokinetics, and preliminary activity of QXL138AM in subjects with locally advanced un-resectable and/or metastatic solid tumors and multiple myeloma. The study is an open-label, multicenter, first in human study to be conducted in two major parts which are further organized into two sub-parts. Part A Dose Escalation is a modified 3+3 with the first two cohorts consisting of one subject each based on the low clinical starting dose. Dose escalation in solid tumors (Part A1) will be followed by dose finding in multiple myeloma (Part A2). Part B consists of dose expansion in solid tumors (Part B1) and multiple myeloma (Part B2) using the recommended dose for expansion from Part A

Eligibility Criteria

Inclusion

Inclusion Criteria:

  1. Participants with Solid Tumors
  • Histopathologically confirmed diagnosis of an advanced, unresectable, ormetastatic solid tumor (ovarian, pancreatic, urothelial, renal, hepatocellular,gastrointestinal (GI), lung, prostate, and breast cancer).

  • Have progressed despite standard therapies, or for whom conventional therapy isnot effective or tolerable, as judged by the Investigator. Patients must haveno available therapeutic options known to confer clinical benefit for theirtumor type.

  1. Participants with Multiple Myeloma
  • Have progressed despite standard therapies, or for whom conventional therapy isnot effective or tolerable, as judged by the Investigator.

  • Patients must have failed at least 3 prior therapies for myeloma and shouldhave had prior exposure to a proteosome inhibitor, an IMiD, and ananti-CD38-directed therapy.

  1. Male or female participants ≥18 years of age at the time of informed consent 3. AnEastern Cooperative Oncology Group (ECOG) performance status scale of 0, 1, or 2 atScreening 4. Must have at least 1 measurable lesion by RECIST version 1.1 (solidtumors only), or evaluable disease by IMWG Uniform Response Criteria (multiplemyeloma only) 5. Adequate organ function and bone marrow reserve 6. Adequate cardiacfunction as estimated by left ventricular ejection fraction 7. Female participantsof child-bearing potential must:
  • Have a negative serum pregnancy test at screening and a negative pregnancy test atWeek 1 Day 1 prior to first dose of QXL138AM, AND

  • Agree to use at least 1 highly effective method of contraception for the duration ofstudy participation, and for 120 days after last dose of QXL138AM.

  1. Male participants of child-bearing potential must:
  • Agree to use at least 1 highly effective method of contraception for the duration ofstudy participation, and for 120 days after last dose of QXL138AM, AND

  • Refrain from sperm donation prior to the first dose of investigational productthrough 120 days following the last dose of QXL138AM.

Exclusion

Exclusion Criteria:

  1. New York Heart Association Class III or IV cardiac disease, myocardial infarctionwithin the past 6 months, unstable arrhythmia, a history of risk factors forTorsades de Pointes (TdP), including heart failure, hypokalemia, and family historyof long QTc syndrome, or evidence of ischemia on ECG. Symptomatic ischemic heart disease or unstable angina pectoris; or history ofcardiac angioplasty, cardiac stenting, or coronary artery bypass graft. A clinicallysignificant baseline prolongation of QT/QTcF interval at screening.

  2. The use of concomitant medications that may significantly prolong the QT/QTcinterval.

  3. Active, uncontrolled bacterial, viral, or fungal infections requiring systemictherapy.

  4. Known hypersensitivity to the investigational product or components (anti-CD138 IgG1antibody, Interferon A2a and/or the formulation excipients: histidine, sucrose,arginine, polysorbate 80).

  5. Female participant is lactating.

  6. Any other clinically significant comorbidities.

  7. Received prior anticancer therapy within 28 days or 5x the half-life (whichever isshorter) prior to the first dose of investigational product.

  8. Participants who received wide-field radiation therapy within 4 weeks prior to firstdose of investigational product, (2 weeks for limited field radiation therapy)

  9. Major surgery within 30 days before first dose of investigational product

  10. Chronic use of systemic corticosteroids of more than 20 mg/day of prednisone orequivalent.

  11. Active, clinically significant liver disease such as Hepatitis B or C, autoimmunehepatitis, or cirrhosis (Child Hugh Stage B or C).

  12. Current or history of mood disorder such as major depression per DSM-5 within pasttwo years not controlled with current therapy.

  13. Active autoimmune disorders not controlled with current therapy.

  14. Active endocrine disorders including hypothyroidism, hyperthyroidism, hypoglycemia,hyperglycemia, and diabetes mellitus not controlled with current therapy.

Study Design

Total Participants: 100
Treatment Group(s): 1
Primary Treatment: QXL138AM Injection every 2 weeks by IV Infusion
Phase: 1
Study Start date:
August 28, 2024
Estimated Completion Date:
May 30, 2028

Study Description

This is an open-label, multicenter, first in human (FIH) Phase 1a/1b study of QXL138AM in participants with locally advanced unresectable and/or metastatic solid tumors and multiple myeloma. This study will be conducted in two parts (A and B) and each part has two sub-parts for tumor type (1 and 2).

Part A1 - Dose Escalation in Solid Tumors The following solid tumor types will initially be enrolled in this part: ovarian, pancreatic, urothelial, renal, hepatocellular, gastrointestinal, lung, prostate, and breast cancer.

Dose escalation will use a standard 3+3 design, where 3 to 6 participants with advanced solid tumors will be enrolled sequentially into each cohort/dose level with the exception of Cohort 1 and 2. For Cohorts 1 and 2, given the very low starting dose, only one participant is planned for each level unless a participant experiences a Grade 2 or higher adverse event not clearly and incontrovertibly related to disease progression or an extraneous factor. If such a Grade 2 or higher event occurs in Cohort 1 or 2, dose escalation will switch to a standard 3+3 design. Dose escalation will continue until the MTD or RDE is determined in participants with solid tumors, referred to as the RDE-ST. At this point, the two solid tumor types for dose expansion will be selected for Part B1 and may begin at the RDE-ST.

The proposed dose levels are defined in the table below. Cohort No. of Participants Dose Level (Q2W) (mg/kg)

  1. 1-6 0.001

  2. 1-6 0.003

  3. 3-6 0.01

  4. 3-6 0.03

  5. 3-6 0.1

  6. 3-6 0.3

  7. 3-6 1

  8. 3-6 2

  9. 3-6 4 Infusions will be administered via syringe pump or IV bag (depending on the dose) and administered over a 30-60-minute (± 10 minutes) duration.

Part A2 - Dose Escalation in Multiple Myeloma Dose escalation in multiple myeloma will commence when the RDE-ST for solid tumors has been identified, or if there are signs of anti-tumor activity in Part A1 as determined by the Sponsor.

Dose escalation will use a standard 3+3 design, where 3 to 6 participants with multiple myeloma will be enrolled sequentially into dose escalation cohorts starting at one dose level below the RDE-ST determined from solid tumor dose escalation (RDE-ST-1). Alternatively, if signs of anti-tumor activity in Part A1 are observed, the Sponsor may elect to initiate dose escalation in multiple myeloma at one dose level below the highest dose already deemed safe in Part A1. If two of the first six participants in the first multiple myeloma cohort experience a DLT, then the dose will be further reduced by one level (RDE-ST-2). Once the RDE for multiple myeloma patients is determined, it will be referred to as the RDE-MM and dose expansion may begin in patients with multiple myeloma at this dose.

Part B1: Dose Expansion in Solid Tumors When the RDE-ST has been identified by the SRC from Part A1, the study may continue to Part B1 dose expansion to further explore the safety and anti-tumor activity of QXL138AM in solid tumors. Dose expansion will enroll two cohorts of 20 participants each in two solid tumor indications identified from Part A1. In each cohort, patients will be randomized 1:1 to receive the RDE-ST dose or 1 dose lower. The Sponsor may opt to enroll additional participants up to a maximum of 40 in each cohort if signs of anti-tumor activity are observed.

Part B2: Dose Expansion in Multiple Myeloma When the RDE-MM in multiple myeloma has been identified by the SRC from Part A2, the study may continue to Part B2 dose expansion to further explore the safety and anti-tumor activity of QXL138AM in patients with multiple myeloma. Up to 20 participants will be treated at the RDE-MM identified in Part A2. Patients will be randomized 1:1 to receive the RDE-MM dose or 1 dose lower.

Connect with a study center

  • Cedars-Sanai Medical Center - Samuel Oschin Comprehensive Cancer

    Los Angeles, California 90048
    United States

    Site Not Available

  • University of Southern California

    Los Angeles, California 90033
    United States

    Site Not Available

  • Hoag Memorial Hospital Presbyterian

    Newport, California 92663
    United States

    Site Not Available

  • Sarah Cannon Research Institute - Denver DDU

    Denver, Colorado 80218
    United States

    Site Not Available

  • Emory University - Winship Cancer Institute

    Atlanta, Georgia 30322
    United States

    Site Not Available

  • New York Cancer & Blood Specialists

    New York, New York 11967
    United States

    Site Not Available

  • University of Rochester - Wilmot Cancer Institute

    Rochester, New York 14642
    United States

    Site Not Available

  • START San Antonio

    San Antonio, Texas 78229
    United States

    Active - Recruiting

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