BNT211-01: This study is evaluating how safe and effective a a new anti-cancer drug is alone, or in addition to another drug, in people with CLDN6-positive relapsed or refractory advanced solid cancersPhase I/IIa, First-in-human (FIH), Open-label, Dose Escalation Trial With Expansion Cohorts to Evaluate Safety and Preliminary Efficacy of CLDN6 CAR-T With or Without CLDN6 RNA-LPX in Patients With CLDN6-positive Relapsed or Refractory Advanced Solid Tumors

Exclusion

Phase 1 of the trial

• Has received prior CAR-T therapy, except CLDN6 CAR-T/CLDN6 CAR-T(A) therapy.
• Has received vaccination with live virus vaccines within 6 weeks prior to the start of lymphodepletion (LD).
• Receives concurrent systemic (oral or i.v.) steroid therapy > 10 mg prednisolone daily, or its equivalent, for an underlying condition.
• Has side effects of any prior therapy or procedures for any medical condition not recovered to national cancer institute (NCI) common terminology criteria for adverse events (CTCAE v.5) Grade ≤ 1.

Medical conditions:

• Current evidence of new or growing brain or spinal metastases during screening. Patients with known brain or spinal metastases may be eligible if they:

  1. Have had radiotherapy or another appropriate therapy for the brain or spinal metastases,
  2. Have no neurological symptoms,
  3. Have stable brain or spinal disease on the computer tomography (CT) or magnetic resonance imaging (MRI) scan within 4 weeks before signing of the ICF,
  4. Are not undergoing acute corticosteroid therapy or steroid taper. Chronic steroid therapy is acceptable provided that the dose is stable for the last 14 days prior to screening (≤ 10 mg prednisolone daily or equivalent),
  5. Do not require steroid therapy within 7 days before the first dose of CLDN6 CAR-T/CLDN6 CAR-T(A),
  6. Have anticipated imminent fracture or cord compression due to spinal bone metastases.
• Has history of epilepsy. Isolated seizures in the past or febrile seizures in childhood are permitted; has a history of a cerebrovascular accident or transient ischemic attack less than 6 months ago.
• Pericardial effusion requiring any drainage is excluded.
• Has an active autoimmune disease including but not limited to inflammatory bowel disease, systemic lupus erythematosus, ankylosing spondylitis, scleroderma, or multiple sclerosis. Has any active immunologic disorder requiring immunosuppression with steroids or other immunosuppressive agents with the exception of patients with isolated vitiligo, resolved childhood asthma or atopic dermatitis, controlled hypoadrenalism or hypopituitarism, and euthyroid patients with a history of Grave's disease. Patients with controlled hyperthyroidism must be negative for thyroglobulin, thyroid peroxidase antibodies, and thyroid-stimulating immunoglobulin prior to trial drug administration.
• Seropositivity for human immunodeficiency virus (HIV).
• Known history/positive serology for hepatitis B requiring active antiviral therapy (unless immune due to vaccination or resolved natural infection or unless passive immunization due to immunoglobulin therapy). Patients with positive serology must have hepatitis B virus viral load below the limit of quantification.
• Active hepatitis C virus (HCV) infection; patients who have completed curative antiviral treatment with HCV viral load below the limit of quantification are allowed.
• Has a known hypersensitivity to a component of CLDN6 CAR-T/CLDN6 CAR-T(A) or CLDN6 (mod)RNA-LPX cancer vaccine drug product, or another similar compound.
• Only for patients recruited for Part 2 with LD chemotherapy (CLDN6 CAR-T/CLDN6 CAR-T(A) + CLDN6 (mod)RNA-LPX with LD chemotherapy): history of severe immediate hypersensitivity reaction to LD chemotherapy consisting of cyclophosphamide or fludarabine.
• Has a history of another primary cancer within the 2 years prior to enrollment except for the following: Non-melanoma skin cancer, cervical carcinoma in situ, superficial bladder cancer, prostate cancer with currently undetectable prostate specific antigen, or other non-metastatic carcinoma that has been in complete remission without treatment for more than 2 years.
• Receipt of allogenic stem cell transplantation in the 5 years prior to enrollment into the trial.
• Patients with acute or chronic graft versus host disease.

Other comorbidities:

• Has abnormal electrocardiograms (ECGs) that are clinically significant, such as QT prolongation.

• In the opinion of the Investigator, has any concurrent conditions that could pose an undue medical hazard or interfere with the interpretation of the trial results; these conditions include, but are not limited to:

  1. Ongoing or active infection requiring antibiotic/antiviral/antifungal therapy
  2. Concurrent congestive heart failure (New York Heart Association Functional Classification Class III or IV)
  3. Concurrent unstable angina
  4. Concurrent cardiac arrhythmia requiring treatment (excluding asymptomatic atrial fibrillation)
  5. Acute coronary syndrome within the previous 6 months
  6. Significant pulmonary disease (shortness of breath at rest or on mild exertion) for example due concurrent severe obstructive pulmonary disease.
• Has a cognitive, psychological or psychosocial impediment that would impair the ability of the patient to receive therapy according to the protocol or adversely affect the ability of the patient to comply with the informed consent process, protocol, or protocol-required visits and procedures.
• Is pregnant or breastfeeding.