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OncoMatch/Clinical Trials/NCT05999396

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

Is NCT05999396 recruiting? Yes, currently enrolling (May 2026). This Phase 1 trial studies Administration of CC-3 for colorectal cancer.

Phase 1RecruitingGerman Cancer Research CenterNCT05999396Data as of May 2026

Treatment: Administration of CC-3This 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.

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Extracted eligibility criteria

Cancer type

Colorectal Cancer

Breast Carcinoma

Sarcoma

Penile Carcinoma

Biomarker criteria

Required: RAS wild-type

anti-EGFR mAb (the latter, if RAS-wild-type and left sided tumors)

Allowed: BRAF V600E

patients BRAF V600E mutation patients should have received: Cetuximab in combination with encorafenib in second- or third-line treatment

Allowed: MMR deficient

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.

Disease stage

Metastatic disease required

Performance status

ECOG 0–2(Ambulatory, capable of self-care)

Prior therapy

Must have received: cytotoxic chemotherapy (FOLFOX, FOLFIRI, FOLFOXIRI, TAS-102, regorafenib) — metastatic

Patients with progressing metastatic CRC who were previously treated with FOLFOX, FOLFIRI, FOLFOXIRI, TAS-102, or regorafenib

Must have received: anti-VEGFR monoclonal antibody — metastatic

if applicable in combination with anti-VEGFR monoclonal antibody (mAb)

Must have received: anti-EGFR monoclonal antibody — metastatic

anti-EGFR mAb (the latter, if RAS-wild-type and left sided tumors)

Must have received: checkpoint inhibitor

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.

Must have received: anti-EGFR monoclonal antibody (cetuximab) — second- or third-line

Cetuximab in combination with encorafenib in second- or third-line treatment

Must have received: BRAF inhibitor (encorafenib) — second- or third-line

Cetuximab in combination with encorafenib in second- or third-line treatment

Cannot have received: investigational anticancer therapy

Concurrent or previous treatment within 30 days in another interventional clinical trial with an investigational anticancer therapy

Cannot have received: systemic chemotherapy

Exception: within 2 weeks prior to study treatment

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

Cannot have received: monoclonal antibody

Exception: within 4 weeks prior to study treatment

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

Cannot have received: radiation therapy

Exception: within 2 weeks prior to study treatment

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

Lab requirements

Blood counts

Hemoglobin ≥ 9 g/dl (transfusion allowed); Neutrophil count ≥ 1,500/mm3; Platelet count ≥ 75,000/µl

Kidney function

Serum creatinine ≤ 1.5mg/dl or creatinine clearance ≥ 60ml/min

Liver function

Bilirubin ≤ 1.5x ULN (no hepatic mets), ≤ 2.5x ULN (with hepatic mets); ALT/AST ≤ 2.5x ULN (no hepatic mets), ≤ 5x ULN (with hepatic mets)

Adequate bone marrow, renal, and hepatic function defined by laboratory tests within 14 days prior to study treatment

Structured fields extracted by AI. May contain errors — verify against the official protocol.

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