Updated June 2026 · ClinicalTrials.gov

RECRUITINGPhase 1INTERVENTIONAL

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

First in Human Clinical Trial to Evaluate the Safety, Tolerability and Preliminary Efficacy of the Bispecific CD276xCD3 Antibody CC-3 in Patients With Colorectal Cancer

FIH, Bispecific CD276xCD3 Antibody CC-3 in Patients With Colorectal Cancer (NCT05999396) is a Phase 1 interventional studying Colorectal Cancer and Breast Carcinoma, sponsored by German Cancer Research Center. RECRUITING as of the most recent ClinicalTrials.gov update. Talk to your doctor before contacting the trial site.

About This Trial

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.

What Stage of Research Is This?

Phase 1 trials test a new treatment for the first time in humans, focusing on safety, dosing, and how the body processes the drug. For Colorectal Cancer, a Phase 1 study typically enrolls a small number of participants — often healthy volunteers or patients who have exhausted standard treatment options. Phase 1 results determine whether a treatment moves into larger Phase 2 efficacy studies.

This trial is currently recruiting participants. The sponsor has registered the study with ClinicalTrials.gov as actively enrolling, which means new applicants who meet the eligibility criteria can be considered for screening. Trial status can change between updates — confirm current recruiting status with the study contact before traveling for a screening visit.

Target enrollment of 89 participants puts this in the typical range for a Phase 2-style efficacy study or a moderate Phase 3 trial in a focused Colorectal Cancer subpopulation. At this scale, the study has enough statistical power to detect a clear treatment effect but is not the largest cohort in the field.

Who May Be Eligible (Plain English)

Who May Qualify: written signed willing to sign a consent form - 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 willing to sign a consent form 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: - blood count (hemoglobin) at least 9 g/dl (Transfusion of packed red blood cells prior to enrolment allowed) - Neutrophil count ≥ 1,500/mm3 ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

These are translations of the protocol\'s inclusion and exclusion criteria, simplified for patients and caregivers. The original clinical text appears below. Eligibility is ultimately confirmed by the trial site\'s screening process — this summary is a starting point for a conversation with your doctor, not a final determination.

Original Eligibility Criteria

View original clinical language

Inclusion Criteria: 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 * Serum creatinine ≤ 1.5mg/dl or creatinine clearance ≥ 60ml/min * hepatic function of patients without current hepatic metastasis: * Bilirubin ≤ 1.5x upper limit of normal (ULN), in case of known Gilbert syndrome higher values are allowed if due to increase of indirect bilirubin * ALT and AST ≤ 2.5 x ULN * hepatic function of patients with current hepatic metastasis: * Bilirubin ≤ 2.5 x upper limit of normal (ULN) * ALT and AST ≤ 5. x ULN Exclusion Criteria: * 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 * Live and live-attenuated vaccination 30 days prior to treatment * Pregnant or breast-feeding women * Current ileus with severely altered GI function

Treatments Being Tested

DRUG

Administration of CC-3

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

Locations (1)

Trial sites listed on ClinicalTrials.gov for this study. Site activation status can vary — confirm with the specific site before traveling for a screening visit.

University Hospital Tuebingen

Tübingen, Baden-Wurttemberg, Germany

How to Talk to Your Doctor About This Trial

Bring the printable summary of this trial — including the NCT ID (NCT05999396), the sponsor (German Cancer Research Center), and the key eligibility criteria — to your next appointment. Your doctor can review the inclusion and exclusion criteria against your medical history, lab values, and current treatments to assess whether you are likely to qualify. They can also help you weigh whether trial participation makes sense alongside your existing care plan.

Useful questions to walk through together: What does the trial protocol require beyond standard care? How long is the active treatment phase, and how long is follow-up? Are there study visits at sites I can reach? Who pays for the trial-specific procedures, and who pays for standard-of-care portions? See our 25 questions to ask about clinical trials guide for a more complete checklist.

Authoritative Sources

The official record for this trial lives on ClinicalTrials.gov — the federal registry maintained by the National Library of Medicine at NIH. For background on how this trial fits into the FDA approval pathway, see the FDA drug approval process. For oncology-specific guidance for patients considering trials, the National Cancer Institute publishes patient-oriented overviews. International trial registries are aggregated by the WHO ICTRP.

Frequently Asked Questions

What is the NCT05999396 clinical trial studying?

Who can participate in NCT05999396?

Eligibility for this trial depends on the specific inclusion and exclusion criteria set by the sponsor. The plain-English summary above translates the most important criteria into accessible language; the official clinical text is preserved in the collapsible section underneath. Whether you fit any specific trial is a medical decision your doctor needs to confirm — bring the trial information to your treating physician for a full review against your medical history.

How do I contact the trial site for NCT05999396?

Contact information registered with ClinicalTrials.gov is shown in the sidebar of this page. Before reaching out, confirm with your treating physician that this trial is appropriate for your situation. The trial site will then walk you through the screening process to determine final eligibility.

Is participating in a clinical trial safe?

Clinical trials in the United States are regulated by the FDA and overseen by Institutional Review Boards (IRBs) that review the protocol for safety. Risk varies by trial — Phase 1 studies test new treatments in humans for the first time, while Phase 3 trials use treatments that have already passed earlier safety screening. The informed consent document for any specific trial details the known risks and what to expect. Discuss those risks with your physician before deciding whether to participate.

Where can I verify the data on this page?

Every detail on this page comes directly from the ClinicalTrials.gov API. Click "View on ClinicalTrials.gov" in the sidebar to see the official, unmodified record. The federal record is always authoritative; this page is a structured presentation with a plain-English eligibility translation. For background on how clinical trials are regulated, see the FDA drug approval process documentation.

How This Page Is Built

Every field on this page is pulled directly from the ClinicalTrials.gov API v2 — no estimates, no proxies. The plain-English eligibility translation is generated from the original protocol text and reviewed for fidelity to the underlying clinical criteria. The original clinical text remains visible in the collapsible section above so users and clinicians can verify the translation. Read the full methodology for the data pipeline and known limitations.

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Source: ClinicalTrials.gov API v2 record for NCT05999396. Maintained by the National Library of Medicine at NIH. Public domain. Cite as: "TrialFinderData. NCT05999396. Data: ClinicalTrials.gov."

Medical disclaimer: This page is informational, not medical advice. Talk to your doctor about whether a clinical trial is right for you.

Last updated 2026-06-26 · Data from ClinicalTrials.gov.