P1, N=133, Completed, Boehringer Ingelheim | Active, not recruiting --> Completed

P1, N=133, Active, not recruiting, Boehringer Ingelheim | Trial completion date: Dec 2023 --> Apr 2024

Mollugin treatment caused obvious decrease in cell viability and proliferation in CRC cells, which were aggravated by ferroptosis inducer erastin and attenuated by ferroptosis inhibitor ferrostatin-1...Further investigation indicated that the IGF2BP3/glutathione peroxidase 4 (GPX4) axis was involved in mollugin-regulated ferroptosis in CRC. In conclusions, Mollugin suppresses proliferation and drives ferroptosis of CRC cells by inhibiting the IGF2BP3/GPX4 axis, suggesting that mollugin may be a potential therapeutic option for CRC.

Xentuzumab plus enzalutamide was tolerable but lacked antitumour activity in unselected patients with mCRPC.

P1, N=133, Active, not recruiting, Boehringer Ingelheim | Trial completion date: Aug 2023 --> Dec 2023

While this study demonstrated that xentuzumab could be safely combined with everolimus and exemestane in patients with HR-positive/HER2-negative advanced breast cancer with non-visceral disease, there was no PFS benefit with the addition of xentuzumab. Trial registration ClinicalTrials.gov, NCT03659136. Prospectively registered, September 6, 2018.

The antitumor effect of xentuzumab (a monoclonal antibody targeting IGF1/2) alone or in combination with the conventional therapeutic agent cisplatin was assessed in HB cell lines, in PDX-derived HB organoids and in a xenograft HB murine model. These results suggest that IGF2 is an HB actionable driver and that, in preclinical models of HB, the combination of IGF1/2 inhibition with cisplatin induces superior antitumor effects than cisplatin monotherapy. Overall, our study provides a rationale for testing IGF2 inhibitors in combination with cisplatin in HB patients with IGF2 overexpression.

We found that inhibition of IGF2BP1 is sufficient to decrease the resistance of chemotherapy-resistant cancer cells with activated Wnt/β-catenin signaling pathway. These findings portray IGF2BP1 as a good candidate for CRC therapy.

Further, LIF treatment enhanced cultured NPC proliferation, which was reduced by picropodophyllin, an IGF-1 receptor inhibitor, even under LIF supplementation. Our findings suggest that IGF expression and release from the NPCs of the fetal cerebrum in fetal CSF is induced by LIF, thus supporting the involvement of the LIF-IGF axis in cerebral cortical development in an autocrine/paracrine manner.

2 million UW-BCC1 cells were injected subcutaneously in the back of 30 immunocompromised mice (Foxn1nu), and they were fed doxycycline supplemented chow. Tumor growth was monitored weekly for eight weeks. Knockdown of IGF2BP1 in UW-BCC1 cells significantly reduced tumor growth in xenograft mice compared to controls (P

P2, N=103, Completed, Boehringer Ingelheim | Active, not recruiting --> Completed

P1, N=164, Completed, Boehringer Ingelheim | Active, not recruiting --> Completed

Xentuzumab monotherapy was well tolerated in Japanese patients and showed evidence of anti-tumor activity. This study was registered with www.clinicaltrials.gov (NCT02145741).

Aiming to exploit this effect in therapy we performed a compound screen in five breast cancer cell lines with IGF neutralising antibody xentuzumab...Exogenous RRM2 expression rescued hallmarks of replication stress induced by co-inhibiting IGF with CHK1 or WEE1, identifying RRM2 as a critical target of the functional IGF:CHK1 and IGF:WEE1 interactions. These data identify novel therapeutic vulnerabilities and may inform future trials of IGF inhibitory drugs.

No abstract available

P2, N=103, Active, not recruiting, Boehringer Ingelheim | Trial completion date: Nov 2022 --> Mar 2022 | Trial primary completion date: Dec 2021 --> Aug 2021

P1, N=133, Active, not recruiting, Boehringer Ingelheim | Recruiting --> Active, not recruiting

The most common drug-related adverse events were diarrhea (75 %), paronychia (69 %), and rash (69 %) in part A and diarrhea (31 %), rash (19 %), paronychia (19 %), and fatigue (19 %) in part B. There were no new safety issues; xentuzumab and afatinib could be safely coadministered. Nevertheless, the combination revealed only modest activity in patients with EGFR mutation-positive, T790M-negative NSCLC after progression on afatinib.

In conclusion, IGF2-AS is a tumor-suppressor in HCC, and lower IGF2-AS expression is associated with poor prognosis of HCC patients; IGF2-AS inhibits HCC oncogenesis and development by IGF2-AS/miR-520h/CDKN1A pathway. Therefore, IGF2-AS may serve as a new biomarker for HCC management.

P1, N=164, Active, not recruiting, Boehringer Ingelheim | Trial completion date: Jul 2021 --> Jan 2022

P1, N=148, Recruiting, Boehringer Ingelheim | Trial completion date: Apr 2023 --> Jul 2023 | Trial primary completion date: Nov 2022 --> Feb 2023

Combining xentuzumab, an insulin-like growth factor (IGF) ligand-neutralizing antibody, with ET and everolimus, suggested progression-free survival (PFS) benefit in pts with advanced HR+ BC and non-visceral disease . Xentuzumab plus abemaciclib and fulvestrant demonstrated encouraging disease control in pts with advanced HR+ BC with visceral and non-visceral disease . The safety profile was manageable, and consistent with the known profiles of the three agents.

P2, N=100, Recruiting, Boehringer Ingelheim | Active, not recruiting --> Recruiting

P2, N=103, Active, not recruiting, Boehringer Ingelheim | Recruiting --> Active, not recruiting

P1, N=148, Recruiting, Boehringer Ingelheim | Trial completion date: Jan 2023 --> Apr 2023 | Trial primary completion date: Aug 2022 --> Nov 2022

P1, N=164, Active, not recruiting, Boehringer Ingelheim | Trial completion date: Nov 2020 --> Jul 2021

P1, N=148, Recruiting, Boehringer Ingelheim | Trial completion date: Jun 2022 --> Jan 2023 | Trial primary completion date: Jan 2022 --> Aug 2022

P1, N=148, Recruiting, Boehringer Ingelheim | Suspended --> Recruiting

P2, N=80, Suspended, Boehringer Ingelheim | Recruiting --> Suspended

P1, N=164, Active, not recruiting, Boehringer Ingelheim | Trial completion date: Jan 2020 --> Sep 2020