FIH, Bispecific CD276xCD3 Antibody CC-3 in Patients With Colorectal Cancer

NCT05999396 | Recruiting Phase 1 DMC

• 1 other identifier: CoRe_CC-3
• Study Type: interventional
• Target: 89
• Locations: 1 country
• Sites: 1

Brief Summary

This trial is a first in human (FIH) clinical trial in patients with Colorectal cancer (CRC) after failure of at least three lines of previous therapy aiming to evaluate safety and efficacy of CC-3, a bispecific antibody (bsAb) with CD276xCD3 specificity developed within DKTK. CC-3 binds to CD276 on cancer cells as well as to tumor vessels of CRC, thereby allowing for a dual mode of anti-cancer action. CC-3 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. A similar construct in this format with PSMAxCD3 specificity is presently undergoing clinical evaluation in patients with prostate cancer (NCT04104607), with very favorable safety and preliminary efficacy. The optimized format that CC-3 shares with its PSMAxCD3 "sister molecule" allows for application of effective bsAb doses with expected high anticancer activity. The clinical trial comprises two phases: The first phase is a dose-escalation part to evaluate the maximally tolerated dose (MTD) of CC-3. This is followed by a dose-expansion part to defined the recommended phase II dose. A translational research program comprising, among others, analysis of CC-3 half-life and the induced immune response will serve to better define the mode of action of CC-3.

Conditions

Colorectal Cancer; Breast Carcinoma; Sarcoma; Penile Carcinoma

Keywords

new therapy; bispecific antibody; colorectal cancer

Outcome Measures

Primary Outcomes (6)

• Safety 1-Adverse Events Assessment

  Dose escalation and dose expansion part: Characterization of the safety of CC-3 in patients with metastasized CRC, and to define the recommended phase-II dose (RP2D) of CC-3 Adverse events should be documented and recorded continuously. Patients have to be followed for AEs from visit T1V1( treatment week1 Visit 1) up to last clinical trial visit or until all drug-related toxicities have been resolved, whichever is later, or until the investigator assesses AEs as "chronic" or "stable". Each occurrence of an AE must be reported once indicating the CTC (Version 5.0) grade. If the CTC grading of an ongoing AE changes this has to be reported. If an event stops and later restarts, all occurrences must be reported. AEs will be coded using the Medical Dictionary for Regulatory Activities (MedDRA®) v26.0 or higher. All AEs will be graded according to the CTCAEv5.0, except for cytokine release syndrome, which will be graded according to modified criteria by Lee et al. (Lee et al., 2019).

  Day 1 Day 2 Day 3 Day 8 +/- 1 day Day 9 Day 15 +/- 1 day Every 7 days +/- 2 days after Treatment week 3 7 days +/- 2 days after last CC-3 28 days +/- 2 days after last CC-3 28 days after FU +/- 3 days

• Safety 2 -Blood Chemistry-Transaminases

  AST/SGOT in \[U/l\] ALT/SGPT in \[U/l)

  Day 1 Day 2 Day 3 Day 8 +/- 1 day Day 9 Day 15 +/- 1 day Every 7 days +/- 2 days after Treatment week 3 7 days +/- 2 days after last CC-3 28 days +/- 2 days after last CC-3 28 days after FU +/- 3 days

• Safety 3-Hematology-haemoglobin

  haemoglobin in \[g/l\]

  Day 1 Day 2 Day 3 Day 8 +/- 1 day Day 9 Day 15 +/- 1 day Every 7 days +/- 2 days after Treatment week 3 7 days +/- 2 days after last CC-3 28 days +/- 2 days after last CC-3 28 days after FU +/- 3 days

• Safety 3-Hematology-Red Blood Cells

  RBC in \[cells/µl\]

  Day 1 Day 2 Day 3 Day 8 +/- 1 day Day 9 Day 15 +/- 1 day Every 7 days +/- 2 days after Treatment week 3 7 days +/- 2 days after last CC-3 28 days +/- 2 days after last CC-3 28 days after FU +/- 3 days

• Safety 3-Hematology-thrombocytes

  PLT in \[cells/µl\]

  Day 1 Day 2 Day 3 Day 8 +/- 1 day Day 9 Day 15 +/- 1 day Every 7 days +/- 2 days after Treatment week 3 7 days +/- 2 days after last CC-3 28 days +/- 2 days after last CC-3 28 days after FU +/- 3 days

• Safety 3-Hematology-White Blood Cells

  WBC in \[cells/µl\]

  Day 1 Day 2 Day 3 Day 8 +/- 1 day Day 9 Day 15 +/- 1 day Every 7 days +/- 2 days after Treatment week 3 7 days +/- 2 days after last CC-3 28 days +/- 2 days after last CC-3 28 days after FU +/- 3 days

Study Arms (1)

Administration of CC-3, a bispecific CD276xCD3 antibody

EXPERIMENTAL

The DL in the accelerated titration phase is fixed in each patient and is applied once per week. The start dose for the first patient is 20µg. Dose increase in the next patient is determined by SRC, comprised of investigators and Sponsor, and can be up to 100% based on safety, PK and PD data. Accelerated titration is terminated and switched to a standard 3 + 3 design in case of any AE Grade ≥ 2 (except AEs unequivocally due to underlying disease or an extraneous cause), occurrence of DLT or decision of SRC based on PK, PD, and safety data. In the dose expansion part, additional patients are treated to have 20 evaluabale patients at the MTD level defined in the dose escalation part.

Drug: Administration of CC-3

Interventions

Administration of CC-3 DRUG

Accelerated titration phase, Standard 3+3 titration phase, expansion phase

Administration of CC-3, a bispecific CD276xCD3 antibody

Eligibility Criteria

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

You may qualify if:

• written signed informed consent
• Patient is able to understand and comply with the protocol for the duration of the clinical trial including undergoing treatment and scheduled visits and examinations
• Patients with progressing metastatic CRC who were previously treated with FOLFOX, FOLFIRI, FOLFOXIRI, TAS-102, or regorafenib, if applicable in combination with anti-VEGFR monoclonal antibody (mAb) and anti-EGFR mAb (the latter, if RAS-wild-type and left sided tumors).
• In case of MSI-high/dMMR tumors, patients should have received checkpoint inhibitor therapy and at least two further lines of therapy of that stated above.
• In case of patients BRAF V600E mutation patients should have received: Cetuximab in combination with encorafenib in second- or third-line treatment.
• At least one measurable lesion that can be accurately assessed at baseline by CT or MRI and is suitable for repeated assessment per RECIST 1.1.
• Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2
• Patient aged ≥ 18, no upper limit
• Female patients of child bearing potential (FCBP) 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 2 months after last dose of study drug.
• For FCBP two negative pregnancy test (sensitivity of at least 25 mU/ml) prior to first application of CC-3
• All subjects must agree to refrain from donating blood while on study drug and for 2 months after last dose of CC-3.
• Adequate bone marrow, renal, and hepatic function defined by laboratory tests within 14 days prior to study treatment:
• Hemoglobin ≥ 9 g/dl (Transfusion of packed red blood cells prior to enrolment allowed)
• Neutrophil count ≥ 1,500/mm3
• Platelet count ≥ 75,000/µl

You may not qualify if:

• Other malignancy requiring treatment within the last year except: adequately treated non-melanoma skin cancer and low-grade non-muscle invasive papillary bladder cancer.
• 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
• Clinical signs of active infection (\> grade 2 according to CTCAE version 5.0)
• Known cerebral/meningeal manifestation of CRC
• History of HIV infection
• Viral active or chronic hepatitis (HBV or HCV)
• Ongoing 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)
• 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, mAb or radiotherapy within 2 (for mAb 4) weeks prior to study treatment or a longer period depending on the defined characteristics of the agents used
• Heart failure NYHA III/IV
• Severe obstructive or restrictive ventilation disorder
• Known intolerance to CC-3 or other immunoglobulin drug products as well as hypersensitivity to any of the excipients present in CC-3

Sponsors & Collaborators

• German Cancer Research Center: lead

Study Sites (1)

University Hospital Tuebingen

Tübingen, Baden-Wurttemberg, 72076, Germany

RECRUITING

Related Publications (1)

• Ott JM, Gassenmaier V, Bitzer M, Schurch CM, Heitmann JS, Hagelstein I. B7-H3: a consistent marker in metastatic colorectal cancer with potential for targeted treatment. Pathol Oncol Res. 2025 Aug 13;31:1612186. doi: 10.3389/pore.2025.1612186. eCollection 2025.

  PMID: 40881578 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms; Breast Neoplasms; Sarcoma; Penile Neoplasms

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Genital Neoplasms, Male; Urogenital Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Penile Diseases; Male Urogenital Diseases

Central Study Contacts

Juliane Walz, Prof. Dr.

CONTACT

+49 7071 29; kketi@med.uni-tuebingen.de

Jonas Heitmann, Dr.

CONTACT

+49 7071 29; kketi@med.uni-tuebingen.de

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 part, Phase I clinical trial, designed to gain evidence of maximally tolerated and recommended phase-II dose of CC-3 in adult patients with CRC.

Study Record Dates

• First Submitted: July 20, 2023
• First Posted: August 21, 2023
• Study Start: January 12, 2024
• Primary Completion (Estimated): October 30, 2026
• Study Completion (Estimated): March 31, 2027
• Last Updated: May 21, 2025

Record last verified: 2025-03

Locations

DE (1)