Trial Title:
A Phase 1/2 Study of KSQ-004EX, Autologous Tumor Infiltrating Lymphocytes Engineered to Inactivate Genes Encoding SOCS1 and Regnase-1, in Patients With Select Advanced Solid Tumors
NCT ID:
NCT06598371
Condition:
Select Advanced Solid Tumors
Conditions: Official terms:
Neoplasms
Cyclophosphamide
Fludarabine
Interleukin-2
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Cyclophosphamide
Description:
Given by IV
Arm group label:
Backfill IL-2: Treatment with Lymphodepletion and KSQ-004EX + IL-2
Arm group label:
Phase 1 mLDC: Treatment with Modified Lymphodepletion and KSQ-004EX
Arm group label:
Phase 1/Phase 2: Treatment with Lymphodepletion and KSQ-004EX
Intervention type:
Drug
Intervention name:
Fludarabine
Description:
Given by IV
Arm group label:
Backfill IL-2: Treatment with Lymphodepletion and KSQ-004EX + IL-2
Arm group label:
Phase 1 mLDC: Treatment with Modified Lymphodepletion and KSQ-004EX
Arm group label:
Phase 1/Phase 2: Treatment with Lymphodepletion and KSQ-004EX
Intervention type:
Drug
Intervention name:
KSQ-004EX
Description:
Given by IV
Arm group label:
Backfill IL-2: Treatment with Lymphodepletion and KSQ-004EX + IL-2
Arm group label:
Phase 1 mLDC: Treatment with Modified Lymphodepletion and KSQ-004EX
Arm group label:
Phase 1/Phase 2: Treatment with Lymphodepletion and KSQ-004EX
Intervention type:
Drug
Intervention name:
Interleukin-2
Description:
Given by IV
Arm group label:
Backfill IL-2: Treatment with Lymphodepletion and KSQ-004EX + IL-2
Other name:
IL-2
Summary:
Phase 1 is to find the recommended dose of KSQ-004EX to give to participants with
advanced solid tumors.
Phase 2 is to learn if KSQ-004EX at the recommended dose found in Phase1 can help to
control advanced solid tumors.
The safety and effects of KSQ-004EX will also be studied in both phases.
Detailed description:
Phase 1: Dose Escalation
Primary Objective:
- To evaluate the safety and tolerability of KSQ-004EX in adult participants with
advanced solid tumors (melanoma, NSCLC, HNSCC, CRC, pancreatic cancer, and cervical
cancer) Secondary Objectives
- Determine expansion dose
- Assess the safety and tolerability of KSQ-004EX in participants with advanced solid
tumors (melanoma, NSCLC, HNSCC, CRC, pancreatic cancer, and cervical cancer)
- Evaluate preliminary anti-tumor activity of KSQ-004EX in participants with advanced
solid tumors
- Evaluate the feasibility of the manufacturing process
Phase 2: Expansion Primary Objective
- To assess the anti-tumor activity of KSQ-004EX in participants with advanced
malignant solid tumors Secondary Objectives
- Assess the safety and tolerability of KSQ-004EX in participants with advanced solid
tumors (melanoma, NSCLC, HNSCC, CRC, pancreatic cancer, and cervical cancer)
- Evaluate anti-tumor activity of KSQ-004EX in participants with advanced malignant
solid tumors
- Evaluate overall survival (OS)
- Evaluate the feasibility of the manufacturing process
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Diagnosed with one of the following tumor types:
1. Unresectable, incurable and/or metastatic histologically and/or cytologically
confirmed cutaneous, acral, or unknown primary melanoma (Stage IIIC or Stage
IV) that has progressed following at least 1 and no more than 3 lines of prior
therapy in the advanced/metastatic setting, one of which includes treatment
with anti-PD-1/PD-L1 inhibitor alone or in combination with anti-cytotoxic T
lymphocyte associated protein 4 (anti-CTLA-4) inhibitor or in combination with
anti-LAG-3 antibody.
Note: Up to 5 mucosal patients can be treated in the melanoma expansion cohort
only.
2. Histologically and/or cytologically confirmed primary diagnosis of NSCLC which
has progressed on at least 1 line and no more than 4 lines of prior therapy in
the advanced/metastatic setting, including platinum-based chemotherapy and
checkpoint inhibitor therapy (either given in combination or sequentially).
i. Participants with tumors that have known actionable molecular alteration such as
epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), ROS-1,
B-Raf proto-oncogene (BRAF), rearranged during transfection (RET), MET and Kirsten
Rat Sarcoma Virus (KRAS) must have progressed on standard directed molecular therapy
in addition to platinum-based chemotherapy.
Note, the following do not count towards a line of prior therapy:
- Any therapy/regimen discontinued due to intolerance/tolerability issues
- Retreatment with the same class or previous class of treatment alone or in
combination c. Locally advanced recurrent and/or metastatic histologically
and/or cytologically confirmed HNSCC that has been previously treated with at
least 1 and no more than 4 lines of prior therapy in the advanced/metastatic
setting.
i. Participants must have received a platinum-containing chemotherapy regimen
for the treatment of primary tumor in locally advanced, or metastatic setting
d. Advanced, metastatic histologically and/or cytologically confirmed
colorectal adenocarcinoma that has progressed following at least 1 and no more
than 3 lines of prior therapy. Participants with dMMR/MSI-H or KRASG12C BRAF
V600E mutation must have progressed on standard directed therapy.
e. Locally advanced, recurrent, or metastatic histologically and/or
cytologically confirmed pancreatic ductal adenocarcinoma (PDAC) that has
progressed following at least 1 and no more than 3 lines of prior therapy in
the advanced/metastatic setting.
f. Recurrent, metastatic, or persistent histologically and/or cytologically
confirmed squamous cell carcinoma (SCC), adenosquamous carcinoma, or
adenocarcinoma of the cervix that is not amenable to curative treatment with
surgery and/or radiation therapy that has progressed following at least 1 and
no more than 3 lines of prior therapy in the advanced/metastatic setting.
2. Resectable lesion for KSQ-004EX manufacturing (tumor ≥ 1.5 cm2 or at least 5 core
needle biopsies)
3. At least one measurable lesion per RECIST v1.1 (Eisenhauer 2009) following tumor
resection for KSQ-004EX manufacturing Note: Lesions in previously irradiated areas
should not be selected as a target lesion unless radiation treatment was ≥ 3 months
prior, and there has been demonstrated disease progression in the lesion
4. Age ≥ 18 years of age
5. Life expectancy of ≥ 12 weeks
6. Recovered to ≤ Grade 1 or Baseline toxicity (except alopecia, neuropathy, and
endocrinopathies from prior immunotherapy) from prior therapy (per the National
Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE])
7. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
8. Adequate bone marrow function defined as:
1. Absolute neutrophil count (ANC) of ≥ 1 × 109/L
2. Platelet count of ≥ 100.0 × 109/L
3. Hemoglobin of ≥ 9.0 g/dL
9. Adequate renal function defined as calculated creatinine clearance (Cockcroft-Gault)
≥ 40 mL/min
10. Adequate hepatic function defined as:
1. Total bilirubin ≤ 2.0 × upper limit of normal (ULN) unless associated with
Gilbert's syndrome
2. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 × ULN
(or ≤ 5 × ULN in patients with liver metastases)
11. Washout period from prior anticancer therapy(ies) of a minimum duration (excluding
bridging therapy per concomitant medication, see Section 6.11) is required prior to
the first study treatment (i.e., start of LDC therapy) as detailed below:
1. Targeted therapy: prior targeted therapy with an EGFR, ALK, receptor tyrosine
kinase, or other-directed agent (eg, erlotinib, afatinib, osimertinib,
crizotinib, ceritinib), is allowed provided the washout is a minimum of 7 days
or 5 half-lives, whichever is longer prior to start of therapy (LDC)
2. Monoclonal antibodies with a washout of at least 21 days or 5 half-lives or
whichever is longer
3. Chemotherapy: adjuvant, neoadjuvant or definitive chemotherapy/chemoradiation
is allowed provided the washout is a minimum of 21 days or 5 half-lives,
whichever is shorter
4. Radiation therapy: prior external beam radiation is allowed provided a minimum
of 14 days have elapsed between the last dose of radiation and first study
treatment (LDC)
5. Surgery: previous surgical procedure(s) is permitted provided that wound
healing has occurred and at least 14 days have elapsed (for major operative
procedures) prior to the first study treatment (LDC)
12. Female participants who are women of childbearing potential (WOCP), (defined as
physiologically and anatomically capable of becoming pregnant), confirmed of a
negative pregnancy test and agreement to the use of a highly effective contraceptive
method or at least 2 effective methods at the same time during study treatment
period and for up to 3 months after study treatment (KSQ-004EX infusion). Male
participants must be willing to use effective barrier contraception (ie, condoms)
during the study treatment period and for up 3 months after study treatment
(KSQ-004EX infusion)
a. This includes all female participants, between the onset of menses (as early as 8
years of age) and 55 years unless the participant presents with an applicable
exclusionary factor which may be one of the following: i. Postmenopausal (no menses
in greater than or equal to 12 consecutive months).
ii. History of hysterectomy or bilateral salpingo-oophorectomy. iii. Ovarian failure
(follicle stimulating hormone and estradiol in menopausal range, who have received
whole pelvic radiation therapy).
iv. History of bilateral tubal ligation or another surgical sterilization procedure.
b. Approved methods of birth control are as follows: hormonal contraception (ie,
birth control pills, injection, implant, transdermal patch, vaginal ring),
intrauterine device (IUD), tubal Ligation or hysterectomy, subject/partner
post-vasectomy, implantable or injectable contraceptives, and condoms plus
spermicide. Not engaging in sexual activity for the total duration of the trial and
the drug washout period is an acceptable practice; however periodic abstinence, the
rhythm method, and the withdrawal method are not acceptable methods of birth
control. Should a woman become pregnant or suspect she is pregnant while she or her
partner is participating in this study, she should inform her treating physician
immediately.
13. Ability to understand and the willingness to sign a written informed consent
document
14. Signed and dated Institutional Review Board (IRB) approved informed consent form
(ICF) before any protocol-directed Screening procedures are performed
Exclusion Criteria:
1. Prior organ allograft or prior cell therapy that included LDC or myeloablative
chemotherapy regimen
2. Known hypersensitivity to any component of KSQ-004EX or excipient including dimethyl
sulfoxide, human serum albumin, LDC regimen (cyclophosphamide or fludarabine) or
IL-2 (as applicable)
3. Active or prior documented autoimmune or inflammatory disorders (including
inflammatory bowel disease [eg, Grade ≥ 2 colitis or Crohn's disease], systemic
lupus erythematosus, sarcoidosis syndrome, or Wegener syndrome [granulomatosis with
polyangiitis], rheumatoid arthritis, etc.]). The following are exceptions to this
criterion:
1. Participants with vitiligo or alopecia
2. Participants with hypothyroidism (eg, following Hashimoto syndrome) stable on
hormone replacement
3. Any chronic skin condition that does not require systemic therapy
4. Participants with celiac disease controlled by diet alone
4. Hypersensitivity to antibiotics of the aminoglycoside group (eg, streptomycin,
gentamicin) or penicillin
5. Active, uncontrolled concurrent infection requiring IV antibiotics present at
Screening
6. Uveal and/or ocular melanoma
7. Large cell neuroendocrine NSCLC (defined as pathology with >10% neuroendocrine
components)
8. Symptomatic and/or untreated brain metastases (of any size or number) including
active leptomeningeal or parenchymal metastases.
Note: Participants with definitively treated brain metastases may be considered for
enrollment if stable (defined as stable for 1-month post-central nervous system
directed therapy) after discussion with the drug provider (KSQ)
9. Participants with ascites
10. Women who are pregnant or nursing
11. Seropositive for human immunodeficiency virus (HIV) 1 or 2 or acquired
immunodeficiency syndrome, or active infection with hepatitis B virus (HBV) or
hepatitis C virus (HCV) Note: Participants with positive HCV antibody may be
eligible if HCV ribonucleic acid (RNA) is undetectable on a quantitative HCV RNA
assay, following discussion with the drug provider (KSQ)
12. Any form of primary immunodeficiency (eg, Severe Combined Immunodeficiency Disease)
13. Any known clinically significant or concurrent acute liver disease, including viral
hepatitis
14. Previous solid organ or hematopoietic cell transplant
15. Need for treatment with steroids at stable doses (> 10 mg/day prednisone or
equivalent)
1. Topical, ophthalmic, or inhaled steroid medications are allowed
2. Systemic steroid (>10 mg/day) use is not allowed for 14 days prior to
enrollment
3. Systemic steroids < 10 mg/day are permitted if for supplemental endocrine only
Note: steroids can be administered for IV contrast allergy
16. Live or unattenuated vaccine < 28 days prior to first dose of LDC regimen
17. History of stroke, transient ischemic attack, unstable angina, or myocardial
infarction, within 3 months prior to first dose of study treatment
18. Symptomatic congestive heart failure according to New York Heart Association (NYHA)
classification, Class III or IV (per NYHA Classification), unstable angina pectoris,
clinically significant cardia arrhythmia, or left ventricular ejection fraction <
45%
19. Prolongation of QT/QTc interval (QTc interval > 480 msec) using the Frederica method
of QTc analysis
20. Unable to walk a distance of 80% predicted for age and sex or develop hypoxia (SPO2
< 90%) during a 6-minute walk test (this test can be performed in place of pulmonary
function test [PFT] for those unable to perform a reliable PFT due to complex upper
airway anatomy)
21. For participants receiving IL-2 only: evidence of ischemia on cardiac stress test
22. > 80% stenosis based on carotid doppler ultrasound for patients with NSCLC and HNSCC
with > 35 pack year smoking history
23. Obstructive or restrictive pulmonary disease Note: Post-bronchodilator values:
forced expiratory volume (FEV1)/forced vital capacity > 70% or FEV1 > 50% of
predicted normal are required for study entry
24. Suspected pneumonitis or interstitial lung disease (confirmed by radiography or
computed tomography [CT])
25. Treatment on another study with other investigational therapeutic interventional
study within 28 days to start of LDC regimen
26. Known additional malignancy that is active and/or progressive requiring treatment;
exceptions including basal cell or squamous cell skin cancer, or other cancer for
which the participants has been disease-free for at least 2 years
27. Psychiatric illness/social situation that would limit compliance with study
requirements, as determined by the Investigator
28. Other severe, acute, or chronic medical condition or laboratory abnormality that may
increase the risk associated with study participation or study drug administration,
or that may interfere with the interpretation of the study results, and in the
judgement of the Investigator, would the participant inappropriate for the study
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
MD Anderson Cancer Center
Address:
City:
Houston
Zip:
77030
Country:
United States
Contact:
Last name:
Rodabe N Amaria, MD
Phone:
713-792-2921
Email:
rnamaria@mdanderson.org
Investigator:
Last name:
Rodabe N Amaria, MD
Email:
Principal Investigator
Start date:
March 11, 2025
Completion date:
August 1, 2041
Lead sponsor:
Agency:
M.D. Anderson Cancer Center
Agency class:
Other
Collaborator:
Agency:
KSQ Therapeutics, Inc.
Agency class:
Industry
Source:
M.D. Anderson Cancer Center
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06598371
https://www.mdanderson.org
