CC-1 / University Hospital Tuebingen - LARVOL DELTA

Identification of BCL family members as modulators of regorafenib efficacy in experimental glioma (EANO 2025) - "RNA sequencing revealed regorafenib-dependent modulation of the Bcl-2 downstream target chemokine receptor 1 (CCR1). We utilized a functional genomics-based target discovery approach with subsequent multi-level validation to identify modulators of regorafenib efficacy. Our findings reveal actionable targets and support the rationale for combinatorial treatment strategies, particularly co-inhibition of Bcl-2 family proteins. These results provide a strong biological rationale for clinical evaluation of regorafenib in combination with navitoclax."

Clinical • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Oncology • Solid Tumor • ARAF • BCL2 • BCL2L1 • FOXC1 • ITGB3

Tumor-targeted CD28 bispecific antibodies enhance the antitumor efficacy of CD3-bispecifics and mitigate T cell exhaustion (AACR 2025) - P1 | "Finally, and perhaps most importantly, BiCo-1 also reverted T cell exhaustion induced by CC-1 single agent treatment in patient-derived T cells ex vivo.Taken together, these data demonstrate that the combinatorial use of bsAbCD3 and Bicos may profoundly enhance the sustainability and specificity of therapeutically induced T cell responses against tumors. The GMP-compliant production of BiCo-1 as well as preclinical evaluation in non-human primates has been completed, and a first-in-human clinical trial in prostate cancer patients is will begin recruitment in 2025."

Clinical • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • ABCD3 • ENG

DKTK_PMO_1605: The Bispecific PSMAxCD3 Antibody CC-1 in Patients with Castration Resistant Prostate Carcinoma (clinicaltrials.gov) - P1 | N=86 | Recruiting | Sponsor: University Hospital Tuebingen | Trial completion date: Dec 2024 ➔ Dec 2025 | Trial primary completion date: Dec 2024 ➔ Dec 2025

Trial completion date • Trial primary completion date • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

ProSperACC-1: Antibody CC-1 in Men With Biochemical Recurrence of Prostate Cancer (clinicaltrials.gov) - P1 | N=56 | Recruiting | Sponsor: University Hospital Tuebingen | Trial completion date: Dec 2025 ➔ Dec 2026 | Trial primary completion date: Dec 2024 ➔ Dec 2025

Trial completion date • Trial primary completion date • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

the Bispecific PSMAxCD3 Antibody CC-1 in Patients With Castration Resistant Prostate Carcinoma (clinicaltrials.gov) - P1 | N=86 | Recruiting | Sponsor: University Hospital Tuebingen | Trial completion date: Aug 2023 ➔ Dec 2024 | Trial primary completion date: Mar 2023 ➔ Dec 2024

Trial completion date • Trial primary completion date • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Bispecific PSMAxCD3 Antibody CC-1 in Patients With Squamous Cell Carcinoma of the Lung (clinicaltrials.gov) - P1/2 | N=3 | Terminated | Sponsor: German Cancer Research Center | N=86 ➔ 3 | Trial completion date: Sep 2025 ➔ May 2023 | Recruiting ➔ Terminated | Trial primary completion date: Mar 2025 ➔ May 2023; premature termination of the trial due to bad recruitment

Checkpoint block • Checkpoint inhibition • Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • FOLH1 • IL6R

ProSperACC-1: Antibody CC-1 in Men With Biochemical Recurrence of Prostate Cancer (clinicaltrials.gov) - P1 | N=56 | Recruiting | Sponsor: University Hospital Tuebingen | Not yet recruiting ➔ Recruiting

Enrollment open • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

ProSperACC-1: Antibody CC-1 in Men With Biochemical Recurrence of Prostate Cancer (clinicaltrials.gov) - P1 | N=56 | Not yet recruiting | Sponsor: University Hospital Tuebingen

New P1 trial • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

the Bispecific PSMAxCD3 Antibody CC-1 in Patients With Castration Resistant Prostate Carcinoma (clinicaltrials.gov) - P1 | N=86 | Recruiting | Sponsor: University Hospital Tuebingen | Trial completion date: Sep 2022 ➔ Aug 2023 | Trial primary completion date: Mar 2022 ➔ Mar 2023

Trial completion date • Trial primary completion date • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • IL2 • IL6

Bispecific PSMAxCD3 Antibody CC-1 in Patients With Squamous Cell Carcinoma of the Lung (clinicaltrials.gov) - P1/2 | N=86 | Recruiting | Sponsor: German Cancer Research Center | Not yet recruiting ➔ Recruiting

Checkpoint inhibition • Enrollment open • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • FOLH1 • IL6R

Bispecific PSMAxCD3 Antibody CC-1 in Patients With Squamous Cell Carcinoma of the Lung (clinicaltrials.gov) - P1/2; N=86; Not yet recruiting; Sponsor: German Cancer Research Center; Trial completion date: Jan 2025 ➔ Sep 2025; Trial primary completion date: May 2023 ➔ Mar 2025

Checkpoint inhibition • Clinical • Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • FOLH1 • IL6R • MRI

Bispecific PSMAxCD3 Antibody CC-1 in Patients With Squamous Cell Carcinoma of the Lung (clinicaltrials.gov) - P1/2; N=86; Not yet recruiting; Sponsor: German Cancer Research Center; Trial completion date: May 2024 ➔ Jan 2025; Initiation date: Sep 2020 ➔ May 2021; Trial primary completion date: Sep 2023 ➔ May 2023

Clinical • Trial completion date • Trial initiation date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • FOLH1 • IL6R

Bispecific PSMAxCD3 Antibody CC-1 in Patients With Squamous Cell Carcinoma of the Lung (clinicaltrials.gov) - P1/2; N=86; Not yet recruiting; Sponsor: German Cancer Research Center

Clinical • New P1/2 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • IL6R

the Bispecific PSMAxCD3 Antibody CC-1 in Patients With Castration Resistant Prostate Carcinoma (clinicaltrials.gov) - P1; N=86; Recruiting; Sponsor: University Hospital Tuebingen; Trial primary completion date: Mar 2020 ➔ Mar 2022

Clinical • Trial primary completion date • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • Urothelial Cancer