ACTolog in Patients With Solid Cancers

SCREENING: Patient eligibility will be determined by HLA (human leukocyte antigen) and the main biomarkers screening. If the patient is eligible, white blood cells will be collected with a leukapheresis for the manufacture of the IMA101 product.

MANUFACTURE: IMA101 product will be made from the patient's white blood cells.

TREATMENT: IMA101 product will be administered to the patient intravenously after lymphodepleting pre-conditioning with chemotherapy (fludarabine and cyclophosphamide).

Low-dose IL-2 will be self-administered twice daily for a total of 28 doses after infusion of IMA101 product. In Cohort 2, atezolizumab will be administered every 3 weeks, starting no earlier than 3 weeks after the IMA101 product infusion and after hematologic recovery.

Patients will be monitored closely throughout the study.

Inclusion criteria

• Patients must have pathologically confirmed advanced/metastatic cancer prior to enrollment.
• HLA phenotype positive.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
• Life expectancy > 6 months prior to enrollment.
• Patient is a candidate for a maximum of one further line of established therapy (prior to treatment with ACTolog).
• The patient has adequate organ and marrow function per protocol
• At least one lesion (metastasis or primary tumor) being considered accessible by non-high-risk collection procedures for biopsy.
• The patient has adequate hepatic function per protocol
• The patient has serum creatinine clearance ≥50 mL/min by the Cockcroft-Gault formula.
• The patient has adequate pulmonary function per protocol
• Acceptable coagulation status
• Women of childbearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation.
• Male subjects must agree to use effective contraception or abstinence while on study and for 90 days after infusion of the ACTolog T-cell product.
• Ability of subject to understand and the willingness to sign written informed consent for study participation.
• Confirmed availability of production capacities for the patient's ACTolog products.
• ACTolog target expression as evaluated by the in vitro diagnostic device IMA_Detect: Patient's tumor must express at least one ACTolog target as assessed by quantitative PCR (qPCR) (to be assessed from a tumor biopsy to be performed if all other eligibility criteria are met).

Exclusion criteria

• Any condition contraindicating leukapheresis.
• Patients with brain metastases. Patients with a history of brain metastases may be eligible, if an imaging scan with contrast enhancement not older than 4 weeks is able to exclude the existence of currently active brain metastasis.
• HIV infection, active Hepatitis B or C infection, or active infections requiring oral or intravenous antibiotics or that can cause a severe disease and pose a severe danger to lab personnel working on patients' blood or tissue. If positive test results are not indicative of an active infection, patients can be included.
• Treatment with excluded therapy per protocol
• Previous extensive radiotherapy to the lung or liver during the last 4 months prior to lymphodepletion regimen.
• The patient has cardiac conditions defined per protocol
• Patients with prior stem cell transplantation or solid organ transplantation.
• The patient has concurrent severe and/or uncontrolled medical disease that could compromise participation in the study
• Active diverticulitis, intra-abdominal abscess, gastrointestinal obstruction, abdominal carcinomatosis or other known risk factors for bowel perforation.
• History of other malignancies (except for adequately treated basal or squamous cell carcinoma or carcinoma in situ) within the last 3 years.
• The patient is pregnant or is breastfeeding.
• Serious autoimmune disease per protocol
• History of hypersensitivity to cyclophosphamide, fludarabine or IL-2.
• Immunosuppression, not related to prior treatment for malignancy.
• History of or current immunodeficiency disease or prior treatment compromising immune function at the discretion of the treating physician.
• Patients with Grade 3 or higher immune-related toxicities related to prior checkpoint inhibitors