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

15 Participants Needed

Trial Summary

What is the purpose of this trial?

To learn if KSQ-001EX is safe to give to participants with advanced forms of solid tumors.

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.

What data supports the idea that KSQ-001EX for Solid Tumors is an effective treatment?

The available research shows that KSQ-001EX, which involves expanding special immune cells called tumor-infiltrating lymphocytes (TILs), is effective because it significantly increases the number of these cells, which are important for fighting cancer. One study found that these cells could be expanded from 2.9 times to over 900 million times their original number, which is a huge increase. Another study showed that using engineered cells to help grow these TILs made them more powerful and effective against tumors. This suggests that KSQ-001EX could be a promising treatment for solid tumors. ^{1 2 3 4 5}

What data supports the effectiveness of the treatment KSQ-001EX for solid tumors?

Research shows that tumor-infiltrating lymphocytes (TILs), which are part of the KSQ-001EX treatment, can be expanded significantly and have strong anti-tumor activity. Studies have demonstrated that these TILs are much more powerful than other immune cells in treating advanced cancers, suggesting potential effectiveness in solid tumors. ^{1 2 3 4 5}

What safety data is available for KSQ-001EX treatment for solid tumors?

The provided research abstracts do not directly address safety data for KSQ-001EX or Engineered Tumor Infiltrating Lymphocytes (eTIL). They focus on the expansion and application of tumor-infiltrating lymphocytes (TILs) in immunotherapy, including methods to enhance TIL expansion and their potential use in clinical trials. However, specific safety data for KSQ-001EX is not mentioned in these abstracts. ^{1 2 3 4 6}

What safety data exists for KSQ-001EX (eTIL) treatment in humans?

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 for KSQ-001EX or eTIL in humans. ^{1 2 3 4 6}

Is the treatment KSQ-001EX for solid tumors a promising treatment?

Yes, KSQ-001EX, which uses engineered tumor-infiltrating lymphocytes (eTIL), is a promising treatment for solid tumors. It helps expand special immune cells that can attack cancer cells more effectively. This treatment has shown strong potential in fighting tumors by increasing the number and strength of these immune cells, making it a hopeful option for cancer therapy. ^{1 2 3 7 8}

What makes the treatment KSQ-001EX unique for solid tumors?

KSQ-001EX is unique because it uses engineered tumor-infiltrating lymphocytes (eTIL), which are specially modified immune cells that can be expanded more efficiently to target and attack cancer cells in solid tumors, potentially offering a more powerful and targeted approach compared to traditional therapies. ^{1 2 3 7 8}

Research Team

Rodabe N. Amaria

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

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

Resectable lesion(s) for KSQ-001EX manufacturing (tumor ≥1.5cm2 or at least 5 core biopsies). At least 1 measurable lesion per RECIST v1.1 following tumor resection for KSQ-001EX manufacturing. Age between 18 - 70 years old. Life expectancy of ≥ 12 weeks. Recovered to ≤ Grade 1 or Baseline toxicity (except alopecia, neuropathy, and endocrinopathies from prior immunotherapy) from prior therapy. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1. Adequate bone marrow function, renal function, and hepatic function. Washout period from prior anticancer therapy(ies) of a minimum duration required prior to the first study treatment. Female participants who are women of childbearing potential must confirm a negative pregnancy test and agree to the use of a highly effective contraceptive method or at least 2 effective methods at the same time during the study treatment period and for up to 3 months after study treatment. Male participants must be willing to use effective barrier contraception during the study treatment period and for up to 3 months after study treatment. Capable of understanding and complying with protocol requirements. Signed and dated Institutional Review Board (IRB) approved informed consent form before any protocol-directed Screening procedures are performed.

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.

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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) 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]

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]

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]

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]

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) 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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Engineered artificial antigen presenting cells facilitate direct and efficient expansion of tumor infiltrating lymphocytes. [2021]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Expansion of human tumor infiltrating lymphocytes for use in immunotherapy trials. [2020]

3. United States pubmed.ncbi.nlm.nih.gov

Augmented lymphocyte expansion from solid tumors with engineered cells for costimulatory enhancement. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Simplified protocol for clinical-grade tumor-infiltrating lymphocyte manufacturing with use of the Wave bioreactor. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Isolation of tumour-reactive lymphocytes from peripheral blood via microfluidic immunomagnetic cell sorting. [2023]

6. China pubmed.ncbi.nlm.nih.gov

[The specific cytotoxic effect of tumor infiltrating lymphocytes transfected with chimeric T cell receptor on cells which express KDR]. [2009]

7. China pubmed.ncbi.nlm.nih.gov

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

8. Germany pubmed.ncbi.nlm.nih.gov

Tumor-infiltrating lymphocytes from nonrenal urological malignancies. [2021]