Trial Title:
Safety, PK and Efficacy of QXL138AM in Patients With Solid Tumors and Multiple Myeloma
NCT ID:
NCT06582017
Condition:
Ovarian Cancer
Pancreas Cancer
Urothelial Carcinoma
Renal Cell Carcinoma
Hepatocellular Carcinoma
Gastrointestinal Cancer
Lung Cancer
Prostate Cancer
Breast Cancer
Conditions: Official terms:
Carcinoma
Multiple Myeloma
Carcinoma, Renal Cell
Gastrointestinal Neoplasms
Pancreatic Neoplasms
Conditions: Keywords:
QXL138AM-001
CD138
Interferon A
Nammi Therapeutics Inc.
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Single Group Assignment
Intervention model description:
Modified 3+3 design
Primary purpose:
Treatment
Masking:
None (Open Label)
Masking description:
Open-label
Intervention:
Intervention type:
Biological
Intervention name:
QXL138AM Injection every 2 weeks by IV Infusion
Description:
masked immuno-cytokine comprised of an anti-CD138 IgG1 antibody fused to human interferon
alpha 2a
Arm group label:
Phase 1a Dose Escalation in Multiple Myeloma - Part A2
Arm group label:
Phase 1a Dose Escalation in Solid Tumors - Part A1
Arm group label:
Phase 1b Dose Expansion in Multiple Myeloma - Part B2
Arm group label:
Phase 1b Dose Expansion in Solid Tumors - Part B1
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
Detailed 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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Participants with Solid Tumors
- Histopathologically confirmed diagnosis of an advanced, unresectable, or
metastatic solid tumor (ovarian, pancreatic, urothelial, renal, hepatocellular,
gastrointestinal (GI), lung, prostate, and breast cancer).
- Have progressed despite standard therapies, or for whom conventional therapy is
not effective or tolerable, as judged by the Investigator. Patients must have
no available therapeutic options known to confer clinical benefit for their
tumor type.
2. Participants with Multiple Myeloma
- Have progressed despite standard therapies, or for whom conventional therapy is
not effective or tolerable, as judged by the Investigator.
- Patients must have failed at least 3 prior therapies for myeloma and should
have had prior exposure to a proteosome inhibitor, an IMiD, and an
anti-CD38-directed therapy.
2. Male or female participants ≥18 years of age at the time of informed consent 3. An
Eastern Cooperative Oncology Group (ECOG) performance status scale of 0, 1, or 2 at
Screening 4. Must have at least 1 measurable lesion by RECIST version 1.1 (solid
tumors only), or evaluable disease by IMWG Uniform Response Criteria (multiple
myeloma only) 5. Adequate organ function and bone marrow reserve 6. Adequate cardiac
function as estimated by left ventricular ejection fraction 7. Female participants
of child-bearing potential must:
- Have a negative serum pregnancy test at screening and a negative pregnancy test at
Week 1 Day 1 prior to first dose of QXL138AM, AND
- Agree to use at least 1 highly effective method of contraception for the duration of
study participation, and for 120 days after last dose of QXL138AM.
8. Male participants of child-bearing potential must:
- Agree to use at least 1 highly effective method of contraception for the duration of
study participation, and for 120 days after last dose of QXL138AM, AND
- Refrain from sperm donation prior to the first dose of investigational product
through 120 days following the last dose of QXL138AM.
Exclusion Criteria:
1. New York Heart Association Class III or IV cardiac disease, myocardial infarction
within the past 6 months, unstable arrhythmia, a history of risk factors for
Torsades de Pointes (TdP), including heart failure, hypokalemia, and family history
of long QTc syndrome, or evidence of ischemia on ECG.
Symptomatic ischemic heart disease or unstable angina pectoris; or history of
cardiac angioplasty, cardiac stenting, or coronary artery bypass graft. A clinically
significant baseline prolongation of QT/QTcF interval at screening.
2. The use of concomitant medications that may significantly prolong the QT/QTc
interval.
3. Active, uncontrolled bacterial, viral, or fungal infections requiring systemic
therapy.
4. Known hypersensitivity to the investigational product or components (anti-CD138 IgG1
antibody, 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 is
shorter) prior to the first dose of investigational product.
8. Participants who received wide-field radiation therapy within 4 weeks prior to first
dose 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 or
equivalent.
11. Active, clinically significant liver disease such as Hepatitis B or C, autoimmune
hepatitis, or cirrhosis (Child Hugh Stage B or C).
12. Current or history of mood disorder such as major depression per DSM-5 within past
two 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.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
University of Southern California
Address:
City:
Los Angeles
Zip:
90033
Country:
United States
Status:
Not yet recruiting
Contact:
Last name:
Anthony El-Khoueiry, MD
Phone:
323-865-3962
Email:
elkhouei@med.usc.edu
Facility:
Name:
Cedars-Sanai Medical Center - Samuel Oschin Comprehensive Cancer
Address:
City:
Los Angeles
Zip:
90048
Country:
United States
Status:
Not yet recruiting
Contact:
Last name:
Kamya Sankar, MD
Phone:
248-802-2041
Email:
kamya.sankar@cshs.org
Facility:
Name:
Hoag Memorial Hospital Presbyterian
Address:
City:
Newport
Zip:
92663
Country:
United States
Status:
Not yet recruiting
Contact:
Last name:
Benjamin Goldenson, MD
Phone:
949-764-4060
Email:
Benjamin.Goldenson@Hoag.org
Facility:
Name:
Sarah Cannon Research Institute - Denver DDU
Address:
City:
Denver
Zip:
80218
Country:
United States
Status:
Not yet recruiting
Contact:
Last name:
Jason T Henry, MD
Phone:
720-754-2610
Email:
Jason.Henry2@SarahCannon.com
Facility:
Name:
Emory University - Winship Cancer Institute
Address:
City:
Atlanta
Zip:
30322
Country:
United States
Status:
Not yet recruiting
Contact:
Last name:
Fatemeh Ardeshir, MD
Phone:
404-778-0202
Email:
fatemeh.ardeshir.larijani@emory.edu
Facility:
Name:
New York Cancer & Blood Specialists
Address:
City:
New York
Zip:
11967
Country:
United States
Status:
Not yet recruiting
Contact:
Last name:
Richard Zuniga, MD
Phone:
613-675-5075
Email:
zunigaresearch@nycancer.com
Facility:
Name:
University of Rochester - Wilmot Cancer Institute
Address:
City:
Rochester
Zip:
14642
Country:
United States
Status:
Not yet recruiting
Contact:
Last name:
Brea Lipe, MD
Phone:
585-276-6302
Email:
brea_lipe@urmc.rochester.edu
Facility:
Name:
START San Antonio
Address:
City:
San Antonio
Zip:
78229
Country:
United States
Status:
Recruiting
Contact:
Last name:
Drew Drasco, MD
Phone:
210-593-5258
Email:
drasco@startsa.com
Start date:
August 28, 2024
Completion date:
May 30, 2028
Lead sponsor:
Agency:
Nammi Therapeutics Inc
Agency class:
Industry
Source:
Nammi Therapeutics Inc
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06582017
