Membrane-anchored IL-12–modified TIL (attIL12-TIL) therapy for advanced soft tissue and bone sarcoma

T Cell Membrane-Anchored Tumor-Targeted IL12 -Modified TIL Cell Therapy (attIL12-TIL) for Advanced/Metastatic Soft Tissue and Bone Sarcoma Patients.

This trial tries T cells engineered to carry membrane-anchored IL-12 (attIL12-TIL), given with cyclophosphamide, for people with relapsed or metastatic soft tissue or bone sarcomas, with a liposarcoma expansion group.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 40 (estimated)
• Ages: 12 Years and up
• Sex: All
• Sponsor: M.D. Anderson Cancer Center (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy, radiation, cyclophosphamide
• Locations: 1 site (Houston, Texas)
• Trial ID: NCT06474676 on ClinicalTrials.gov

What this trial studies

This is a Phase 1, open-label dose-finding trial that combines autologous tumor-infiltrating lymphocytes engineered to express membrane-anchored IL-12 (attIL12-TIL) with cyclophosphamide. Part A uses a dose-escalation design to determine safety, maximum tolerated dose, and a recommended Phase 2 dose. Part B enrolls an expansion cohort of recurrent unresectable liposarcoma to characterize tolerability and measure preliminary efficacy by the four-month progression-free survival rate. The protocol also includes exploratory immune correlative studies on paired tumor specimens and blood, and analyses of collagen/FAP and CSV-positive circulating tumor cells to link biological changes with clinical outcomes.

Who should consider this trial

Good fit: Ideal candidates are people aged 12 or older with histologically confirmed locally advanced or metastatic soft tissue or bone sarcoma (or unresectable recurrent/metastatic liposarcoma for the expansion cohort) who have measurable disease, have had at least one prior systemic therapy unless none exists for their subtype, and can undergo biopsy or resection for TIL harvest.

Not a fit: Patients without measurable disease, with uncontrolled medical comorbidities, or whose tumors are not amenable to TIL harvest or lack expected target features may not receive benefit from this approach.

Why it matters

Potential benefit: If successful, the approach could improve tumor control and extend progression-free survival for patients with advanced sarcomas, particularly liposarcoma.

How similar studies have performed: While adoptive TIL therapy and systemic IL-12 approaches have shown activity in some solid tumors, the membrane-anchored IL-12 modification (attIL12) is a novel strategy and has limited prior clinical proof specifically in sarcoma.

Eligibility criteria

Inclusion Criteria:

1. Age ≥ 12 years old
2. Histologically-confirmed locally advanced or metastatic soft tissue or bone sarcoma scheduled to undergo resection or biopsy as part of standard of care
3. Liposarcoma expansion cohort: histologically confirmed unresectable recurrent/metastatic liposarcoma scheduled to undergo resection or biopsy as part of standard of care
4. Participants undergoing resection should have other measurable disease or be high risk for recurrence within 12 month per investigator assessment and has prior approval by PI.
5. Measurable disease according to RECIST 1.1 present prior to infusion of attIL12-TIL. If the only measurable disease is the same as the lesion biopsied for the study, it needs to be at least 2 cm in largest diameter.
6. Participants must have received at least 1 prior line of systemic therapy for the treatment of sarcoma, unless no standard therapy exists for a specific sarcoma subtype.
7. At least 3 weeks must have elapsed since the last cytotoxic chemotherapy or immunotherapy prior to tumor tissue collection. For targeted therapies, at least 4 half-lives or 3 weeks must have elapsed prior to tumor tissue collection (whichever is shorter). Standard of care anti- cancer therapy will be permitted following tumor tissue collection but prior to initiation of cyclophosphamide such that at least 3 weeks must have elapsed since last cytotoxic chemotherapy or immunotherapy prior to starting treatment with cyclophosphamide. For targeted therapies, at least 4 half-lives or 3 weeks must have elapsed prior to initiation of treatment with cyclophosphamide (whichever is shorter). Investigational anti-cancer therapy will not be permitted.
8. At least 2 weeks must have elapsed for palliative radiation to any tumor site other than the tumor site identified for tissue collection
9. Participants must have organ and marrow function as defined below
10. Absolute neutrophil count (ANC) \> 1 K/uL, Hemoglobin \> 9 g/dL, Platelets \> 100 K/mm3
11. Serum creatinine \</= 2 mg/dL OR creatinine clearance \> 50 mL/min
12. Aspartic transaminase (AST) . 1.5 x upper limit of normal (ULN), Alanine transaminase (ALT) \</= 1.5 x ULN, Bilirubin ≤ 1.5 x ULN
13. Women of childbearing potential (WOCBP) must agree to use method(s) of contraception: at least one highly effective or two effective accepted methods of contraception to avoid conception throughout the study in such a manner that the risk of pregnancy is minimized. Suggested precautions should be used to minimize the risk or pregnancy for at least 1 month before start of therapy, and while women are on study for up to 3 months after T cell infusion.

    WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or is not postmenopausal
14. Men must be willing and able to use an acceptable method of birth control such as latex condom during the dosing period and for at least 3 months after completion of the study agent administration (T cell infusion) if their sexual partners are WOCBP.
15. Signed Informed Consent and if applicable, pediatric assent

Exclusion Criteria:

1. Known sensitivity to cyclophosphamide and/or study agents
2. Active or prior documented autoimmune disease (including inflammatory bowel disease, celiac disease, Wegener syndrome) within the past 2 years. Participants with childhood atopy or asthma, vitiligo, alopecia, Hashimoto syndrome, Grave's disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded
3. Untreated central nervous system metastatic disease, leptomeningeal disease, or cord compression. Participants previously treated central nervous system metastases that are radiographically and neurologically stable for at least 6 weeks and do not require corticosteroids (of any dose) for symptomatic management for at least 14 days prior to first dose of attIL12-TIL cells are permitted to enroll.
4. Any concurrent chemotherapy, immunotherapy, or biologic or hormonal therapy for cancer treatment at the time of tumor tissue collection or attIL12 TIL cell infusion. Any prior radiation to the tumor site that is being collected for attIL12 TIL production. Palliative radiation to any tumor site within the past 2 weeks. Standard of care anti-cancer therapy will be permitted following tumor tissue collection but prior to initiation of cyclophosphamide as bridging therapy (per section 5.5). Concurrent use of hormones for non-cancer-related conditions (eg, insulin for diabetes and hormone replacement therapy) is acceptable.
5. Unresolved toxicities from prior anticancer therapy, defined as having not resolved to NCI CTCAE v5 Grade 0 or 1 with the exception of alopecia and laboratory values listed per the inclusion criteria. Subjects with irreversible toxicity that is not reasonably expected to be exacerbated by any of the investigational products may be included (eg, hearing loss) after consultation with the PI.
6. History of primary immunodeficiency, solid organ transplantation, or previous clinical diagnosis of tuberculosis.
7. Receipt of live, attenuated vaccine within 28 days prior to the first dose of investigational products.
8. Major surgery (as defined by the investigator) within 4 weeks prior to first dose of treatment. Biopsy as per study protocol is allowed
9. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, unhealed wound, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs from the study agents, or compromise the ability of the participant to give written informed consent. Participants with cognitive impairment, including adults with cognitive impairment such as trisomy 21 or similar conditions are not specifically excluded from participation, such that appropriate written informed consent is obtained from the parent or legal guardian and they are able to complete with the study protocol requirements and treatment.
10. Active concurrent second malignancy
11. Pregnant or lactating women
12. Any positive test result for hepatitis B or C virus indicating acute or chronic infection
13. Known history of testing positive for human immunodeficiency virus or known acquired immunodeficiency syndrome

Where this trial is running

Houston, Texas

• MD Anderson Cancer Center — Houston, Texas, United States (Recruiting)

Study contacts

• Principal investigator: Neeta Somaiah, MBBS — M.D. Anderson Cancer Center
• Study coordinator: Neeta Somaiah, MBBS

Conditions Metastatic Soft-tissue Sarcoma