KSQ-001EX for Solid Tumors

Overseen By Rodabe N Amaria, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Steroids, Antibiotics

Disqualifiers: Autoimmune disorders, Brain metastases, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug called KSQ-001EX (Engineered Tumor Infiltrating Lymphocytes, or eTIL) to determine its safety for individuals with advanced solid tumors unresponsive to standard treatments. It includes various participant groups, such as those with melanoma, non-small cell lung cancer (NSCLC), or head and neck squamous cell carcinoma (HNSCC). Suitable candidates have tumors that cannot be surgically removed or are metastatic and have previously tried standard therapies without success. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new drug.

Do I need to stop my current medications for the trial?

The trial requires a washout period for certain prior anticancer therapies before starting the study treatment. For targeted therapies, monoclonal antibodies, and chemotherapy, a washout of at least 21 days or 5 half-lives (whichever is longer) is needed. Radiation therapy requires a 14-day washout. Systemic steroids over 10 mg/day are not allowed for 14 days before enrollment. The protocol does not specify other medications, so consult with the trial team for guidance on your specific medications.

Will I have to stop taking my current medications?

The trial requires a washout period (time without taking certain medications) from prior anticancer therapies before starting the study treatment. This includes a minimum of 21 days or 5 half-lives for targeted therapies and monoclonal antibodies, and 14 days for radiation therapy. Please consult with the trial team to discuss your specific medications.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that KSQ-001EX remains in the early testing stages to determine its safety and tolerability in humans. This treatment is under investigation for advanced solid tumors, including melanoma, non-small cell lung cancer (NSCLC), and head and neck squamous cell carcinoma (HNSCC). Currently, detailed safety information is limited. However, the trial is in both Phase 1 and Phase 2, focusing on ensuring the treatment's safety for people.

In Phase 1, researchers begin with a small group of participants to identify any serious side effects and establish the appropriate dose. If the treatment progresses to Phase 2, early results suggest it might be safe enough for testing on a larger group.

Overall, KSQ-001EX is under close safety monitoring, and researchers will carefully observe participants for any negative effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about KSQ-001EX for solid tumors because it offers a novel approach compared to existing treatments like chemotherapy, radiation, or immunotherapy. Unlike most treatments, which can be non-specific and affect healthy cells, KSQ-001EX targets specific tumor types, potentially leading to fewer side effects. Additionally, Arm 2 of the trial introduces an innovative dosing schedule of IL-2, aiming to enhance the body's immune response more effectively. This targeted action and unique dosing have the potential to improve treatment outcomes and patient quality of life.

What evidence suggests that KSQ-001EX might be an effective treatment for solid tumors?

Research has shown that KSQ-001EX, a therapy using special immune cells, may help treat advanced cancers such as melanoma, head and neck cancer, and non-small cell lung cancer. In this trial, participants will receive KSQ-001EX in different phases, including a Safety Lead-in phase and an Expansion Phase. Animal studies found that just one dose of this therapy can greatly shrink tumors. This treatment uses modified immune cells to find and destroy cancer cells more effectively. Early studies with patients suggest that this method could improve outcomes for those with difficult-to-treat cancers. While more remains to be learned, the initial results are promising for patients considering this treatment. ^{6 7 8 9 10}

Who Is on the Research Team?

Rodabe N. Amaria

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for people with advanced solid tumors, including melanoma, lung cancer, and head and neck cancers. Participants must meet certain health standards to be eligible.

Inclusion Criteria

My melanoma cannot be surgically removed, has spread, and worsened after treatment including immunotherapy.

My NSCLC has worsened despite standard treatments, including platinum-based chemo and checkpoint inhibitors.

I have HNSCC, treated with 1-3 therapies including platinum and anti-PD-1/PD-L1.

Exclusion Criteria

Prior organ allograft or prior cell therapy that included LDC or myeloablative chemotherapy regimen. Known hypersensitivity to any component of KSQ-001EX or excipient including dimethyl sulfoxide, human serum albumin, LDC regimen (cyclophosphamide or fludarabine) or IL-2 (as applicable). Active or prior documented autoimmune or inflammatory disorders. Uveal and/or ocular melanoma. Large cell neuroendocrine NSCLC. Symptomatic and/or untreated brain metastases. Women who are pregnant or nursing. Seropositive for HIV 1 or 2 or active infection with HBV or HCV. Any form of primary immunodeficiency. Any known clinically significant or concurrent acute liver disease. Previous solid organ or hematopoietic cell transplant. Need for treatment with steroids at stable doses. Live or unattenuated vaccine < 28 days prior to first dose of LDC regimen. History of stroke, transient ischemic attack, unstable angina, or myocardial infarction within 3 months prior to first dose of study treatment. Symptomatic congestive heart failure according to NYHA classification, Class III or IV, unstable angina pectoris, clinically significant cardiac arrhythmia, or left ventricular ejection fraction < 45%. Prolongation of QT/QTc interval. Unable to walk a distance of 80% predicted for age and sex or develop hypoxia during a 6-minute walk test. Obstructive or restrictive pulmonary disease. Treatment on another study with other investigational therapeutic interventional study within 28 days to start of LDC regimen. Known additional malignancy that is active and/or progressive requiring treatment. Psychiatric illness that would limit compliance with study requirements. Other severe, acute, or chronic medical condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1 - Safety Lead-in

Participants receive KSQ-001EX to evaluate safety and tolerability, with IL-2 dosing for some cohorts

6-8 weeks

Multiple visits for dosing and monitoring

Phase 2 - Expansion

Participants are assessed for anti-tumor activity of KSQ-001EX in specific cohorts

12-24 weeks

Regular visits for treatment and assessment

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• KSQ-001EX

Trial Overview The safety of KSQ-001EX (engineered tumor-fighting cells) is being tested in patients with advanced solid tumors. The treatment includes a preparation phase with drugs like Interleukin-2, Cyclophosphamide, and Fludarabine before receiving KSQ-001EX.

How Is the Trial Designed?

Group I: Arm 3: Phase 2- Expansion Phase Experimental Treatment 3 Interventions

It is expected that approximately 20 participants will be enrolled in each of the 3 indication specific cohorts.

Group II: Arm 2: Phase 1- Safety Lead-in (Cohort 2) Experimental Treatment 4 Interventions

Patients in Cohort 2 will receive IL-2 dosing (600,000 international units \[IU\]/kg administered every 8 to 12 hours for up to 6 doses, as tolerated).

Group III: Arm 1: Phase 1- Safety Lead-in (Cohort 1) Experimental Treatment 3 Interventions

Approximately 6 patients with melanoma, NSCLC or HNSCC will be enrolled in the Safety Lead-in phase of the study with a KSQ-001EX dose.

KSQ-001EX is already approved in United States for the following indications:

Approved in United States as KSQ-001EX for:

• Melanoma
• Non-Small Cell Lung Cancer (NSCLC)
• Head and Neck Squamous Cell Carcinoma (HNSCC)

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

KSQ Therapeutics, Inc.

Industry Sponsor

Trials

3

Recruited

410+

Published Research Related to This Trial

Tumor-infiltrating lymphocytes (TIL) have shown to be significantly more effective than other immune cells in treating advanced metastatic tumors, with successful expansion from 24 out of 25 human tumors, including various types of cancers.

The method developed for large-scale expansion of TIL resulted in generating over 10 billion lymphocytes in some cases, and clinical trials using these expanded TIL for treating metastatic disease have already commenced.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Expansion of human tumor infiltrating lymphocytes for use in immunotherapy trials. Topalian, SL., Muul, LM., Solomon, D., et al.[2020]

Transfected tumor infiltrating lymphocytes (TIL) with a chimeric T cell receptor (CTCR) can selectively target and kill cells expressing the KDR receptor, demonstrating a potential mechanism for targeted cancer therapy.

The study showed that TIL expressing the Vhgamma receptor had significant cytotoxic effects on KDR-expressing cells, such as ECV304 and A375, while showing limited effects on non-KDR expressing cells, indicating a specific and effective approach to targeting tumor cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The specific cytotoxic effect of tumor infiltrating lymphocytes transfected with chimeric T cell receptor on cells which express KDR]. Wang, S., Yin, ZF., Cui, ZF., et al.[2009]

Tumor-infiltrating lymphocytes (TIL) can be successfully expanded from various urological cancers, including bladder and prostate cancer, indicating their potential for therapeutic use, as demonstrated in 14 out of 15 samples showing lytic activity against tumor targets.

The study found that TIL growth was better in AIM V medium compared to RPMI, and while the addition of lymphokine-activated killer (LAK) supernatant showed some benefits, it did not enhance TIL culture in AIM V, suggesting that medium choice is crucial for effective TIL expansion.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tumor-infiltrating lymphocytes from nonrenal urological malignancies. Haas, GP., Solomon, D., Rosenberg, SA.[2021]

A new simplified protocol for manufacturing tumor-infiltrating lymphocytes (TILs) using a closed-system bioreactor has been developed, significantly reducing the workload during the TIL expansion process.

This improved method not only produces high-quality TIL products but has also shown to mediate clinical regression in patients with metastatic melanoma, potentially increasing access to this effective treatment globally.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Simplified protocol for clinical-grade tumor-infiltrating lymphocyte manufacturing with use of the Wave bioreactor. Donia, M., Larsen, SM., Met, O., et al.[2021]

Genetically-engineered artificial antigen presenting cells (aAPCs) can rapidly and effectively expand tumor-infiltrating lymphocytes (TILs) from cancer patients, achieving similar results to traditional methods but with a significantly lower feeder cell to TIL ratio.

The expanded TILs using aAPCs are tumor-reactive and maintain a favorable composition, with a higher proportion of CD8+ lymphocytes and lower frequencies of regulatory T cells, making them suitable for adoptive immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Engineered artificial antigen presenting cells facilitate direct and efficient expansion of tumor infiltrating lymphocytes. Ye, Q., Loisiou, M., Levine, BL., et al.[2021]

Tumor-infiltrating lymphocytes (TIL) were successfully isolated from 19 solid tumors, yielding an average of 1.3 million TILs per gram of tumor tissue, which can be expanded significantly (30 to 150 times) using rIL-2 in a four-week cultivation process.

The expanded TILs demonstrated a stronger anti-tumor effect against the patient's own tumors compared to other tumors, indicating their potential for personalized cancer immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The antitumor effects of tumor-infiltrating lymphocytes (TIL) being proliferated in vitro]. Zhang, BX.[2016]

Engineered cells for costimulatory enhancement (ECCE) significantly accelerated the expansion of tumor-infiltrating lymphocytes (TIL) from melanoma biopsies, increasing TIL numbers and improving their antitumor reactivity (P=0.001).

ECCE also enhanced TIL generation from nonmelanoma-cell suspensions, suggesting that this method could broaden access to TIL therapy for patients who are currently ineligible for treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Augmented lymphocyte expansion from solid tumors with engineered cells for costimulatory enhancement. Friedman, KM., Devillier, LE., Feldman, SA., et al.[2023]

Circulating tumour-reactive lymphocytes (cTRLs) can be effectively isolated from peripheral blood using microfluidic immunomagnetic cell sorting, providing a high yield and purity that could overcome challenges in treating patients with unresectable tumours or recurrent metastases.

The study found that CD8+CD103+ cTRLs from blood are as potent as tumour-infiltrating lymphocytes in mice, and they can be expanded to produce immune responses similar to those seen with immune checkpoint blockade, suggesting their potential for use in adoptive cell therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Isolation of tumour-reactive lymphocytes from peripheral blood via microfluidic immunomagnetic cell sorting. Wang, Z., Ahmed, S., Labib, M., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06237881

A Phase 1/2 Study of KSQ-001EX, Autologous Tumor ... Phase I Primary Objectives • To evaluate the safety and tolerability of KSQ-001EX in adult participants with advanced solid tumors (melanoma, HNSCC, NSCLC).

2. ksqtx.com ksqtx.com/press-releases/ksq-therapeutics-announces-fda-clearance-of-ind-application-for-ksq-001ex-a-crispr-cas9-engineered-tumor-infiltrating-lymphocyte-etil-therapy/

KSQ Therapeutics Announces FDA Clearance of IND ... Phase 1/2 clinical study will evaluate the safety, pharmacokinetics, and preliminary efficacy of KSQ-001EX in melanoma, head and neck ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12482274/

Novel tumor-infiltrating lymphocytes therapy in solid tumors Evaluating the safety and efficacy of CRISPR/Cas9-modified tumor infiltrating lymphocytes (GT300) as monotherapy in advanced solid tumors.

4. jitc.bmj.com jitc.bmj.com/content/9/Suppl_2/A198

186 Development of KSQ-001, an engineered TIL (eTIL) ... Results Upon adoptive transfer of a single dose into solid tumor-bearing hosts, mKSQ-001 was found to robustly enhance anti-tumor efficacy and ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S2666636724008017

Tumor-Infiltrating Lymphocyte Therapy for Melanoma and ... This review traces the development of adoptive TIL therapy from the initial human studies in melanoma, through recent advances in studies of other solid tumors.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06237881

NCT06237881 | A Phase 1/2 Study of KSQ-001EX, ... Phase I Primary Objectives • To evaluate the safety and tolerability of KSQ-001EX in adult participants with advanced solid tumors (melanoma, HNSCC, NSCLC).

7. jitc.bmj.com jitc.bmj.com/content/12/Suppl_2/A757

660 A phase 1/2 study of KSQ-001EX: an autologous tumor ... This phase 1/2, single-arm, open-label, study will assess the safety, tolerability, and efficacy of KSQ-001EX in patients with melanoma, NSCLC, and HNSCC.

8. ksqtx.com ksqtx.com/pipeline/

Pipeline KSQ-001EX is an investigational eTIL therapy manufactured using our ExPRESS™ process in which the SOCS1 gene is inactivated by CRISPR/Cas9 gene editing.

9. withpower.com withpower.com/trial/phase-2-neoplasms-6-2024-fefb1

KSQ-001EX for Solid Tumors · Info for Participants The research articles focus on the expansion and use of tumor-infiltrating lymphocytes (TIL) for cancer treatment, but they do not provide specific safety data ...

10. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.TPS2675

A phase 1/2 study of KSQ-004EX: Autologous tumor ... The phase 1/2, single-arm, open-label study will assess the safety, tolerability, and efficacy of KSQ-004EX in patients with select advanced solid tumors.