Bispecific PSMAxCD3 Antibody CC-1 in Patients With Squamous Cell Carcinoma of the Lung

NCT04496674 | Terminated Phase 1 DMC

• 1 other identifier: 2019-004849-32
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 2

Brief Summary

This trial is a phase I study in patients with metastatic non-small-cell lung cancer (NSCLC) after failure of second line therapy aiming to evaluate safety and efficacy of CC-1, a bispecific antibody (bsAb) with PSMAxCD3 specificity developed within DKTK. CC-1 binds to human prostate-specific membrane antigen (PSMA) on tumor cells of squamous cell carcinoma of the lung (SCC) as well as to tumor vessels of SCC, thereby allowing for a dual mode of anti-cancer action. CC-1 was developed in a novel format which not only prolongs serum half-life but most importantly reduces off-target T cell activation with expected fewer side effects. Together with preemptive IL-6 receptor (IL-6R) blockade using tocilizumab, this allows for application of effective bsAb doses with expected high anticancer activity. The study comprises two phases: The first phase is a dose-escalation phase with concomitant prophylactic application of tocilizumab to evaluate the maximally tolerated dose (MTD) of CC-1. This is followed by a dose-expansion phase (also with prophylactic IL-6R blockade using tocilizumab). A translational research program comprising, among others, analysis of CC-1 half-life and the induced immune response as well as molecular profiling in liquid biopsies will serve to better define the mode of action of CC-1 and to identify biomarkers for further clinical development.

Conditions

Lung Cancer Squamous Cell

Keywords

third line therapy; SCC; Metastatic squamous cell cancer

Outcome Measures

Primary Outcomes (2)

• Incidence and severity of adverse events (AEs) (CTCAE V5.0) over 22 days

  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.

  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

• Dose expansion part

  To define the recommended phase-II dose of CC-1 under preemptive IL-6R blockade I

  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

Secondary Outcomes (3)

• Immunogenicity

  day 15, day 43

• Anti-tumor activity

  End of safety follow up,day 22 of cycle 3 and 4

• Survival

  12 month after end of safety follow up

Other Outcomes (3)

• PSMA PET CT

  baseline, End Of safety follow up and at any timepoint dury study treatment if progressive disease is assumed in routine imaging

• Cytokine induction:

  at baseline and at day 1-9, day 15 and day 22 in first cycle.

• Pharmacokonteic

  at day 1-9, day 15 and day 22 in the first cycle.

Study Arms (1)

Treatment with bispecific Ab CC-1

EXPERIMENTAL

administration of bispecific PSAMxCD3 Ab CC-1.

Drug: CC-1 and Toczilizumab

Interventions

CC-1 and Toczilizumab DRUG

Adminsitration of CC-1 and Toczilizumab

Treatment with bispecific Ab CC-1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Existence of a written informed consent
• Patient is able to understand and comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations
• SCC of the lung with detectable PSMA expression by tumor cells after second line treatment. PSMA expression is to be determined by central immunohistochemical assessment of fresh or cryopreserved tumor samples. Only patients with proven PSMA expression by tumor cells as defined by ≥10% positivity of tumor cells can be included.
• Life expectance of \> 3 months
• At least one measurable lesion that can be accurately assessed at baseline by CT or MRI and is suitable for repeated assessment
• Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2
• Patient aged ≥ 18, no upper age limit
• Female patients of child bearing potential and male patients with partners of child bearing potential, who are sexually active, must agree to the use of two effective forms (at least one highly effective method) of contraception. This should be started from the signing of the informed consent and continue throughout period of taking study treatment and for 1 month (female patients) / 3 months (male patients) after last dose of study drug. Postmenopausal or evidence of non-childbearing status. For women of childbearing potential: negative urine or serum pregnancy test within 21 days prior to study treatment and confirmed prior to treatment on day 1. Postmenopausal or evidence of non-childbearing status is defined as:
• Amenorrhoeic for 1 year or more following cessation of exogenous hormonal treatments
• Luteinizing hormone (LH) and Follicle stimulating hormone (FSH) levels in the post menopausal range for women under 50
• Radiation-induced oophorectomy with last menses \>1 year ago
• Chemotherapy-induced menopause with \>1 year interval since last menses
• Surgical sterilisation (bilateral oophorectomy or hysterectomy)
• Adequate bone marrow, renal, and hepatic function defined by laboratory tests within 14 days prior to study treatment:
• Neutrophil count ≥ 1,500/mm3 Platelet count ≥ 100,000/µl Bilirubin ≤ 1.5 x upper limit of normal (ULN) ALT and AST ≤ 2.5 x ULN PT-INR/PTT ≤ 1.5 x ULN Creatine kinase ≤ 2.5 x ULN Serum creatinine ≤ 1.5 mg/dl or creatinine clearance ≥ 60 ml/min

You may not qualify if:

• Other malignancy within the last 5 years except: adequately treated non-melanoma skin cancer, carcinoma in situ of the cervix, carcinoma in situ of the breast, histological finding of prostate cancer of TNM stage T1
• PSMA expression \<10% by tumor cells
• Concurrent or previous treatment within 30 days in another interventional clinical trial with an investigational anticancer therapy
• Persistent toxicity (≥Grade 2 according to Common Terminology Criteria for Adverse Events \[CTCAE\] version 5.0) caused by previous cancer therapy, excluding alopecia and neurotoxicity (≤ 2 grade)
• Clinical signs of active infection (\> grade 2 according to CTCAE version 5.0)
• Cerebral/Meningeal manifestation of the SCC of the lung
• History of HIV infection
• Immunocompromised patients
• Viral active or chronic hepatitis (HBV or HCV)
• History of autoimmune disease
• History of relevant CNS pathology or current relevant CNS pathology (e.g. seizure, paresis, aphasia, cerebrovascular ischemia/hemorrhage, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, psychosis, coordination or movement disorder)
• Epilepsy requiring pharmacologic treatment
• Therapeutic anticoagulation therapy
• Major surgery within 4 weeks of starting study treatment. Patients must have recovered from any effects of major surgery.
• Patients receiving any systemic chemotherapy or radiotherapy within 2 weeks prior to study treatment or a longer period depending on the defined characteristics of the agents used

Sponsors & Collaborators

• German Cancer Research Center: lead
• University Hospital Tuebingen: collaborator

Study Sites (2)

Robert Bosch Centrum für Tumorerkrankungen

Stuttgart, Baden-Wurttemberg, 70376, Germany

Location

University Hospital Tuebingen, CCU Translational Immunology

Tübingen, Baden-Wurttemberg, 72076, Germany

Location

MeSH Terms

Conditions

Neoplasms, Squamous Cell

Condition Hierarchy (Ancestors)

Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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

Study Record Dates

• First Submitted: May 8, 2020
• First Posted: August 3, 2020
• Study Start: February 2, 2022
• Primary Completion: May 3, 2023
• Study Completion: May 3, 2023
• Last Updated: April 23, 2025

Record last verified: 2025-04

Locations

DE (2)