CC-3 / German Cancer Research Center, University of Tuebingen - LARVOL DELTA

Results of the dose escalation phase of a Phase I trial evaluating an optimized bispecific CD276xCD3 antibody for treatment of solid tumors (DGHO 2025) - P1 | "CC-3 is a promising compound with a favourable toxicity profile and promising clinical activity that is expected to increase further with higher dose levels."

P1 data • Breast Cancer • Colorectal Cancer • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • CD276

CD276 (B7-H3) as a Target for T Cell-based Therapy of Penile Cancer (DGHO 2025) - P1 | "Our findings validate CD276 as a target and document the therapeutic efficacy of CC-3 in penile cancer, which warrants the recent inclusion of patients with penile cancer in our ongoing clinical Phase I basket trial"

Genito-urinary Cancer • Oncology • Penile Cancer • Solid Tumor • CD276 • CD69 • IL2RA

Two Targets – Two Signals: Dual Bispecific Antibody Therapy Targeting CD276 and FAP By Engaging CD3 and CD28 for Solid Tumor Immunotherapy (SITC 2025) - P1 | "This molecule is combined with our CD276xCD3 bsAb CC-3, which is presently undergoing clinical investigation as single agent (NCT05999396)...Our dual-signal approach presents a promising strategy to overcome key limitations of CD3-directed bsAb therapy in solid tumors.Ethics Approval The study was approved by the IRB (Ethics Committee of the Medical Faculty of the Eberhard Karls Universitaet Tuebingen) at the University Hospital Tuebingen and was conducted in accordance with the Declaration of Helsinki; reference number 184/2023BO. Human material was collected after informed consent was obtained."

Oncology • Solid Tumor • CD276 • FAP

A bispecific CD276xCD3 antibody for treatment of penile cancer (DGU 2025) - P1 | "Our findings validate CD276 as a target and document the therapeutic efficacy of CC-3 in penile cancer, which warranted inclusion of patients with penile cancer in our ongoing clinical Phase I basket trial."

IO biomarker • Genito-urinary Cancer • Oncology • Penile Cancer • Solid Tumor • CD276

T cell-engaging CD276xCD3 bispecific antibody for treatment of endometrial cancer. (PubMed, J Transl Med) - P1 | "Overall, our findings highlight the potential of CC-3 for clinical evaluation as a therapeutic option for patients with endometrial cancer."

IO biomarker • Journal • Endometrial Cancer • Gynecologic Cancers • Oncology • Solid Tumor • CD276

A Phase II Trial of the Bispecific CD276xcd3 Antibody CC-3 in Breast Cancer Patients with Molecular Relapse (DGS 2025) - P1 | "The Sample Size is based on an estimated rr of ≤25% at 12 months. Secondary Endpoints Include CTDNA Clearance, Time from Ctdna Detection to Relapse, Safety and Quality of Life."

Clinical • P2 data • Breast Cancer • Oncology • Solid Tumor • CD276

Generation and clinical development of an optimized B7-H3xCD3 bispecific antibody for treatment of colorectal and breast cancer (SITC 2024) - P1 | "Furthermore, CC-3 was tested in vivo using immunocompromised mice adoptively transferred with human effector cells with regard to prevention of lung metastasis and flank tumor growth...Ethics Approval The study was approved by IRB (ethics committee of the Faculty of Medicine of the Eberhard Karls Universität Tübingen) at the University Hospital Tübingen and was conducted in accordance with the Declaration of Helsinki; reference numbers 13/2007V, 099/2024BO2, 184/2023BO02. Human material was collected after obtaining informed consent."

Clinical • IO biomarker • Breast Cancer • Colorectal Cancer • Oncology • Solid Tumor • CD276

Clinical development of an optimized bispecific B7H3xCD3 antibody for the treatment of colorectal carcinoma and other tumors (DGHO 2024) - P1 | "CC-3 mediated pronounced antitumor activity in vitro and displayed the expected long half-life and potent antitumor activity in three different mouse models...Key eligibility criteria include diagnosis of progressive metastatic CRC, breast cancer or sarcoma after exhaustion of established treatment options, i.e. for CRC three-lines of therapy consisting of FOLFOX, FOLFIRI, FOLFOXIRI, TAS-102, or regorafenib if applicable, in combination with anti-Vascular Endothelial Growth Factor monoclonal antibody (mAb) and anti-EGFR mAb in RAS-wild-type and left-sided tumors...Secondary endpoints include overall safety, efficacy, survival, quality of life, and pharmacokinetics. Presently, the first three patients have been enrolled."

Clinical • Breast Cancer • Colorectal Cancer • Gastrointestinal Cancer • Gastrointestinal Disorder • Oncology • Sarcoma • Solid Tumor • CD276

Targeting CD276 for T cell-based immunotherapy of breast cancer. (PubMed, J Transl Med) - "Our findings characterize CD276 as promising target and preclinically document the therapeutic potential of CC-3 for BC treatment, providing a strong rationale for evaluation of CC-3 in BC patients in a clinical trial for which the recruitment has recently started."

IO biomarker • Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CD276

B7-H3 as target for T cell-based therapy of breast cancer (CIMT 2024) - "In summary, our findings reveal B7-H3 as promising target in breast cancer and provide evidence that CC-3 has therapeutic potential for this malignancy. Based on these findings, a clinical trial to evaluate CC-3 in patients with breast cancer is presently in preparation."

IO biomarker • Breast Cancer • Gynecology • Obstetrics • Oncology • Solid Tumor • Triple Negative Breast Cancer • IFNG

The bispecific B7H3xCD3 antibody CC-3 induces T cell immunity against bone and soft tissue sarcomas. (PubMed, Front Immunol) - "Finally, CC-3 induced potent target cell lysis in a target cell restricted manner. Based on these results, a clinical trial evaluating CC-3 in soft tissue sarcoma is currently in preparation."

IO biomarker • Journal • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • CD276

IgG based B7-H3xCD3 bispecific antibody for treatment of gynecological tumors (AACR 2024) - "In addition, CC-3 induced efficient T cell proliferation and formation of T cell memory subsets. This resulted in potent target cell lysis.Taken together, our results underscore the potential of CC-3, which is currently in GMP manufacturing, to enable clinical evaluation for the treatment of gynecologic malignancies."

IO biomarker • Colorectal Cancer • Endometrial Cancer • Gastrointestinal Cancer • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor • CD276

Protocol of a 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 (CoRe_CC-3). (PubMed, Front Oncol) - P1 | "Clinical trial results will be published in peer-reviewed journals. Trial registration numbers: ClinicalTrials.cov Registry (NCT05999396) and EU ClinicalTrials Registry (EU trial number 2022-503084-15-00)."

Journal • P1 data • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • CD276

CoRe_CC-3: FIH, Bispecific CD276xCD3 Antibody CC-3 in Patients With Colorectal Cancer (clinicaltrials.gov) - P1 | N=89 | Recruiting | Sponsor: German Cancer Research Center | Not yet recruiting ➔ Recruiting

Enrollment open • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • BRAF

B7-H3xCD3 bispecific antibody as novel treatment option in HER2-negative breast cancer (SITC 2023) - "HER2-targeting antibodies like Trastuzumab have achieved notable success in treatment of HER2-positive breast cancer, whereas antibody-based treatment options for HER2-negative patients remain quite limited. Moreover, CC-3 induced strong T cell proliferation and formation of T cell memory subsets. Conclusions These promising results highlight the therapeutic potential of CC-3 for treatment of HER2-negative breast cancer."

Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • CD276 • HER-2 • IFNG

Generation and clinical development of an optimized B7-H3xCD3 bispecific antibody for treatment of colorectal and other gastrointestinal cancers (DGHO 2023) - "Comprehensive in vitro characterization revealed that targeting the membrane-proximal epitope Q179 of the B7-H3 molecule allowed for a 100-fold reduction of CD3 affinity in our lead compound CC-3 with preserved superior tumor cell killing, efficient T cell activation, proliferation and memory formation, whereas undesired cytokine release was reduced...The trial will consist of a dose escalation part with an accelerated and a standard titration phase to determine the maximum tolerated dose followed by a dose expansion part to define the recommended phase II dose and collect first signs of efficacy. Together, we report on the straight forward development of a novel optimized bsAb from bench to first clinical evaluation that holds promise to improve treatment of CRC patients."

Clinical • Colorectal Cancer • Gastrointestinal Cancer • Gastrointestinal Disorder • Oncology • Solid Tumor • CD276

CoRe_CC-3: FIH, Bispecific CD276xCD3 Antibody CC-3 in Patients With Colorectal Cancer (clinicaltrials.gov) - P1 | N=89 | Not yet recruiting | Sponsor: German Cancer Research Center

New P1 trial • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • BRAF