Bispecific PSMAxCD3 Antibody CC-1 in Patients With Squamous Cell Carcinoma of the Lung
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|ClinicalTrials.gov Identifier: NCT04496674|
Recruitment Status : Recruiting
First Posted : August 3, 2020
Last Update Posted : February 17, 2022
|Condition or disease||Intervention/treatment||Phase|
|Lung Cancer Squamous Cell||Drug: CC-1 and Toczilizumab||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||86 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||Open-label, multicenter dose escalation and dose expansion phase I trial, designed to gain evidence of maximally tolerated and recommended phase-II dose of CC-1 in adult patients with SCC of the lung|
|Masking:||None (Open Label)|
|Official Title:||PPhase-I Study to Evaluate the Safety, Tolerability and Preliminary Efficacy of the Bispecific PSMAxCD3 Antibody CC-1 as Single Agent and Combined With Checkpoint Blockade in Patients With Squamous Cell Carcinoma of the Lung|
|Actual Study Start Date :||February 2, 2022|
|Estimated Primary Completion Date :||March 31, 2025|
|Estimated Study Completion Date :||September 30, 2025|
Experimental: Treatment with bispecific Ab CC-1
administration of bispecific PSAMxCD3 Ab CC-1.
Drug: CC-1 and Toczilizumab
Adminsitration of CC-1 and Toczilizumab
- Incidence and severity of adverse events (AEs) (CTCAE V5.0) over 22 days [ Time Frame: 10-72 patients. at least 1 cycle (for 22 day cycles) plus 21 days follow-up, but may vary depending on treatment-induced clinical benefit and optional additional cycles ]
Incidence and severity of adverse events (AEs) (CTCAE V5.0) over 22 days (i.e. until end of first treatment cycle)
Full hematology assessments for safety hemoglobin, red blood cells, platelets, mean cell volume, mean cell hemoglobin concentration, mean cell hemoglobin, white blood cells, absolute differential white cell count and absolute neutrophil count or segmented neutrophil count and Band forms should be performed at each visit and when clinically indicated.
Biochemistry assessments for safety:
sodium, potassium, calcium, magnesium, glucose, creatinine, total bilirubin, gamma glutamyltransferase, alkaline phosphatase,aspartate transaminase, alanine transaminase, urea or blood urea nitrogen, total protein, albumin and lactic dehydrogenase are performed.
- Dose expansion part [ Time Frame: 14 patients.at least 1 cycle (for 22 day cycles) plus 21 days follow-up, but may vary depending on treatment-induced clinical benefit and optional additional cycles ]
To define the recommended phase-II dose of CC-1 under preemptive IL-6R blockade
- Immunogenicity [ Time Frame: day 15, day 43 ]
Number and percentage of subjects who develop HAHA at day 15 of every cycle and End Of Safety follw-up (day 43 of last cycle of a given patient) as compared to baseline.
n case of CC-1 in this study, AESIs include cytokine-release syndrome (CRS) as the major "class toxicity" for bsAbs, anaphylactic reactions and immunogenicity of the drug substance
With regard to trial schedule and AESI occurrence, AESIs constitute:
- CRS (i.e. within treatment period)
- Anaphylactic reactions upon study drug administration (i.e., within 24h)
- Development of anti-CC-1 antibodies (HAHA) (day 15, day 43)
AESIs are always be addressed as part of the patient safety report to the DSMB, also non-occurrence will be mentioned . Depending on severity of the AESI, dose reduction or discontinuation of treatment (DLT) may be necessary. Of note, allergic /anaphylactic reactions are not defined as DLT.
- Anti-tumor activity [ Time Frame: End of safety follow up,day 22 of cycle 3 and 4 ]
Objective tumor response assessed by RECIST on routine imaging at End of safety follow-up and thereafter for 12 months every 3 months.
• For patients receiving more than one cycle objective tumor response will be assessed by RECIST on additional routine imaging every 6 weeks, i.e. prior to the application of cycle 3 (day 22 +/- 5 days of cycle 2) and cycle 5 (day 22 +/-5 days of cycle 4).
Tumor response rate (TRR) The TRR is defined as the percentage of patients with complete remissions (CR) and partial remissions (PR) according to RECIST version 1.1. The TRR will be assessed at 3 and 6 months, as well as every 3 months during the extended treatment period (compare Trial Schedule). For patients receiving additional treatment cycles TRR will be assessed before the application of cycle 3 (day 22 +/- 5 days of cycle 2) and cycle 5 (day 22 +/-5 days of cycle 4).
- Survival [ Time Frame: 12 month after end of safety follow up ]OS is defined as the time from screening to time of death from any cause. Patients without event are censored at the last date of follow-up.
- PSMA PET CT [ Time Frame: baseline, End Of safety follow up and at any timepoint dury study treatment if progressive disease is assumed in routine imaging ]
Correlation with immunhistochemical proven PSMA expression on tumor at baseline
• Value of PSMA-PET-CT in the context of treatment with CC-1 and progressive disease will be performed in terms of a translational research program to correlate PSMA expression as assessed by cryobiopsy with PSMA imaging. PSMA-PET CT will be performed at baseline, EOSf and at any time point during study treatment (cycle 1-6) if progressive disease is assumed in routine imaging, next imaging will be amended by PSMA-PET. Thus, a minimum of 2 and maximum of 3 PSMA-PET-CTs will be performed per patient.
- Cytokine induction: [ Time Frame: at baseline and at day 1-9, day 15 and day 22 in first cycle. ]Cytokines levels in serum as assessed
- Pharmacokonteic [ Time Frame: at day 1-9, day 15 and day 22 in the first cycle. ]CC-1 serum concentrations assessed
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04496674
|Contact: Helmut Salih, Prof. Dr. med.||+49 (0)7071 29 ext email@example.com|
|Contact: Juliane Walz, Prof Dr. med.||+49 (0)7071 29 ext firstname.lastname@example.org|
|Robert Bosch Centrum für Tumorerkrankungen||Not yet recruiting|
|Stuttgart, BW, Germany, 70376|
|Contact: Hans-Georg Kopp, Prof. Dr. +49 (0)711 8101-2001 email@example.com|
|University Hospital Tuebingen, CCU Translational Immunology||Recruiting|
|Tuebingen, Bw, Germany, 72076|
|Contact: Juliane Walz, Prof. Dr. firstname.lastname@example.org|
|Contact: Jonas Heitmann, Dr. email@example.com|