TF2- Small Cell Lung Cancer Radio Immunotherapy

The purpose of this open-label prospective optimization and phase I/II clinical trial is to examine the safety, optimal dose, targeting, dosimetry and efficacy of PRAIT using the humanized anti-CEA x anti-HSG bsMAb TF2 and the 177Lu-IMP-288 peptide pretargeted in patients with CEA-positive SCLC or CEA-expressing Non Small Cell Lung Carcinoma (NSCLC)

This study has 2 parts: Study plan I (Optimization study) and Study plan II (Escalating activity phase I/II study).

The Study plan I is designed to optimize the pretargeting procedure using blood pharmacokinetics (Pk) and dosimetry in 9 patients receiving escalating doses of TF2 followed 2 to 4 days later by 1.1 GBq/m2 of 177Lu-IMP-288.

The study plan II is designed to determined MTD of 177Lu-IMP-288 using dosimetry and toxicity data in a phase I/II study performed in patients receiving optimal dose of TF2 bsMAb (determined in study plan I) followed 2 to 4 days by escalating activity of 177Lu-IMP-288.

A pre-therapy imaging study (using TF2 followed 2 to 4 days later by 185 MBq of 111In-IMP-288) is performed in the two study plans to qualify a patient for treatment with the subsequent therapy dose.

Inclusion criteria

• Patients with histologic diagnosis of SCLC who are in partial response or who have failed at least two lines of standard radiation and/or chemotherapy. Outside formal contra-indication, patients must have received at least one prior platinum-based chemotherapy.

or

• Patients with histologic diagnosis of NSCLC (without activating mutation of EGFR gene) who have failed at least one line of chemotherapy (platinum in combination with a third generation drug or combination of 2 third generation drug +/-bevacizumab in case of predominance of non-squamous tumor)
• Age ≥ 18 years
• At least 4-weeks after the previous treatment and have recovered from previous radio- or chemotherapy
• Women of child-bearing potential must have a negative pregnancy test.
• Karnofsky performance status ≥ 60 or ECOG performance status 0-2Karnofsky
• Minimum life expectancy of 3 months
• Positive CEA on immunohistology or plasma CEA ≥ 10 ng/mL
• At least one measurable lesion by CT
• At least one abnormal focus by FDG-PET
• Imaging studies must be performed within 1-4 weeks before PRAIT study to document extent of disease
• Signed informed consent form.

Exclusion criteria

• Pregnant or lactating woman. Women of child-bearing potential will be asked to practice adequate means of birth control for a minimum of 12 months after treatment.
• Male patient refusing effective contraception for a minimum of 12 months after treatment.
• Brain metastases but patients with brain metastases controlled after treatment by Surgery or radiotherapy since more than 4 weeks are eligibles for the study. An treatment by associated corticotherapy is authorized for these patients.
• Known HIV or hepatitis
• Any serious active disease or comorbid medical condition (according to the investigator's decision and information provided in the IDB)
• Severe disorders of hemostasis or anticoagulant treatment cure
• Extensive irradiation to more than 25% of their red marrow
• Bone marrow involvement to more than 25%
• External radiation to specific organs or areas at the maximum tolerated level
• EGFR gene mutation in tumor (only for NSCLC)
• Febrile aplasia during a previous chemotherapy
• Neutrophils < 1.5 G/l
• Platelets < 100 G/l
• Uncontrolled diabetes
• Poor renal function (creatinine level > 2.5 maximum normal level)
• Poor hepatic function (total bilirubin level > 30 mmol/l, transaminases > 2.5 maximum normal level)
• Treatment with any investigational drug within 30 days before planned PRAIT and during the study
• Any history of cancer during the last 5 years, with the exception of non-melanoma skin tumors or stage 0 (in situ) cervical carcinoma,
• Presence of anti-antibody reactivity
• Known hypersensitivity to murine antibodies or proteins
• Adult patient unable to give informed consent because of intellectual impairment.