Hotspot TCR-T: A Phase I/Ib Study of Adoptively Transferred T-cell Receptor Gene-engineered T Cells (TCR-T)

Exclusion Criteria

• •1. Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study.
• •2. Receipt of any investigational anticancer therapy during the last 28 days or 5 half-lives, whichever is shorter, prior to the first dose of study treatment. Receipt of any prior anti-CD40 therapy.
• •3. Any concurrent chemotherapy, biologic, or hormonal therapy for cancer treatment, within 21 days (6 weeks for nitrosoureas) or at least 5 half-lives (whichever is longer) prior to the first dose of study treatment. Concurrent use of 4. hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable.
• •5\. Local treatment of isolated lesions for palliative intent is acceptable (e.g., local surgery or radiotherapy), excluding target lesions, Palliative radiation therapy cannot be administered less than 1 week prior to the first dose of study treatment.
• •6\. Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of study drug. Participants must have recovered (to a grade 1 or lower) from all radiation-related toxicities, not require corticosteroids for this purpose and not have had radiation pneumonitis.
• •7\. Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of study treatment. Note: Local surgery of isolated lesions for palliative intent is acceptable.
• •8\. History of organ transplant, including allogeneic stem cell transplantation. 9. History of (non-infectious) pneumonitis/interstitial lung disease or current pneumonitis/interstitial lung disease, including grade 1 pneumonitis (asymptomatic; clinical or diagnostic observation only; intervention not indicated).
• •10\. Uncontrolled intercurrent illness as deemed by the investigator, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, unstable cardiac arrhythmia, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent.
• •11\. History of another primary malignancy except for:
• •Malignancy treated with curative intent and with no known active disease ≥1 year before the first dose of investigational product and of low potential risk for recurrence.
• •Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease (per investigator discretion).
• •Adequately treated carcinoma in situ without evidence of disease (per investigator discretion) 12. History of leptomeningeal carcinomatosis 13. Has untreated central nervous system (CNS) metastases and/or carcinomatous meningitis. Patients whose brain metastases have been treated may participate provided they show radiographic stability (imaging at least four weeks apart showing no evidence of intracranial progression). In addition, any neurologic symptoms that developed either as a result of the brain metastases or their treatment must have resolved or be stable either, without the use of steroids, or are stable on a steroid dose of ≤ 10mg/day of prednisone or its equivalent and anti-seizure medications for at least 14 days prior to the start of treatment. Patients on a stable dose of seizure medicines for epilepsy unrelated to cancer are eligible for the trial.
• •14\. History of active primary immunodeficiency. 15. Active tuberculosis infection (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice).
• •16\. Active autoimmune disease requiring systemic immunosuppression in excess of physiologic maintenance doses of corticosteroids (\> 10 mg/day of prednisone or equivalent).:
• •Autoimmune disease that is not active (in remission), but in the judgment of the investigator could risk substantial morbidity in the event of relapse, may be grounds for exclusion. This can include a prior history of pneumonitis or other autoimmune sequelae of prior immunotherapy.
• •Physiologic corticosteroid replacement therapy at doses \> 10 mg/day of prednisone or equivalent for adrenal or pituitary insufficiency and in the absence of active autoimmune disease is permitted.
• •Participants with asthma that requires intermittent use of bronchodilators, inhaled steroids, or local steroid injections may participate.
• •Participants using topical, ocular, intra-articular, or intranasal steroids (with minimal systemic absorption, per investigator discretion) may participate.
• •17\. Brief courses of corticosteroids for prophylaxis (e.g., contrast dye allergy) or study treatment-related standard premedication are permitted.
• •18\. Receipt of live attenuated vaccine within 28 days prior to the first dose of study treatment. Note: patients should not receive live vaccine during study treatment and up to 30 days after the last dose of study treatment.
• •19\. Known allergy or hypersensitivity to study drug(s) or compounds of similar biologic composition to the study drug(s), or any of the study drug excipients.