dalantercept (ACE-041) / Merck (MSD) - LARVOL DELTA

The DASH Study: A phase 1b study of dalantercept plus sorafenib in advanced hepatocellular carcinoma (ASCO-GI 2015) - Abstract #TPS495; P1/2, N=20; NCT02024087; Sponsor: Acceleron Pharma; "An open label, multi-center, dose escalating, phase 1b study to evaluate dalantercept plus sorafenib in subjects with advanced HCC is ongoing. The primary endpoint includes the evaluation of the safety and tolerability of dalantercept plus sorafenib and determination of the recommended phase 2 dose levels of the combination."

Clinical protocol • Hepatocellular Cancer • Oncology

Advancements in TGF-β Targeting Therapies for Head and Neck Squamous Cell Carcinoma. (PubMed, Cancers (Basel)) - "While preclinical data have demonstrated the great anti-tumorigenic potential of TGF-β inhibitors, the underwhelming results of ongoing and completed clinical trials highlight the difficulty actualizing these benefits into clinical practice. This topical review will discuss the relevant preclinical and clinical findings for TGF-β inhibitors in HNSCC and will explore the potential role of patient stratification in the development of this therapeutic strategy."

Journal • Review • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • TGFB1

Expression of ACVRL1 in a subset of recruited tumor-associated macrophages drives resistance to PD-1 therapy in human breast cancer (SABCS 2022) - "Despite promising preclinical results with a ligand trap (RAP-041/dalantercept), clinical trials did not show additional benefit of dalantercept when combined or contrasted with the standard of care...Finally, survival analysis determined that ACVRL1hi signature in macrophages correlated with a significantly lower survival in a 5-year follow-up in breast cancer. In conclusion, our work sheds light on the value of ALK1 as a promising dual antiangiogenic and immunomodulatory target for precision medicine in cancer."

IO biomarker • Breast Cancer • Oncology • Solid Tumor • ALK1 • TGFB1

Targeting the transforming growth factor-beta signaling pathway in the treatment of gynecologic cancer. (PubMed, Curr Cancer Drug Targets) - "There are several TGF-β inhibitors which are potential anticancer agents and are undergoing clinical trials in cancer, including galunisertib, dalantercept, and vigil. There is a growing body of data showing the potential therapeutic impact of targeting the TGF-β pathway in different cancer types, although further studies are still warranted to explore the value of this strategy and finding the most appropriate patients who could most benefit from therapy."

Journal • Cervical Cancer • Gynecologic Cancers • Oncology • Solid Tumor • TGFB1

Dalantercept in Treating Patients With Recurrent Ovarian Epithelial, Fallopian Tube, or Primary Peritoneal Cavity Cancer (clinicaltrials.gov) - P2; N=30; Completed; Sponsor: Gynecologic Oncology Group; Active, not recruiting ➔ Completed

Clinical • Trial completion • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor • MRI

Study of Dalantercept and Axitinib in Patients With Advanced Renal Cell Carcinoma (clinicaltrials.gov) - P2; N=160; Terminated; Sponsor: Acceleron Pharma Inc.; Completed ➔ Terminated; The study was terminated by the sponsor following unblinding of the Progression Free Survival endpoint.

Clinical • Trial termination • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Systemic therapy for advanced clear cell renal cell carcinoma after discontinuation of immune-oncology and VEGF targeted therapy combinations. (PubMed, BMC Urol) - "Post IO-VEGF, most patients received VEGFR-TKIs. In this setting, VEGFR-TKIs demonstrated clinical activity and remain a viable option for salvage therapy after progression on IO-VEGF."

Journal • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Acceleron’s ACE-041 combined with a VEGF inhibitor shows potent activity in preclinical model of VEGF-resistant renal cell carcinoma (Acceleron) - Acceleron presented preclinical data of ACE-041 in combination with sunitinib, inhibited tumor growth in a model of VEGF-inhibitor-resistant RCC at the AACR annual meeting 2012; P2 studies of ACE-041 in combination with VEGF inhibitors expected later in 2012

Anticipated P2 trial initiation • Data presentation • Oncology • Renal Cell Carcinoma

ALK1/VEGF combo active in advanced RCC (Cancer Network) - "'This study demonstrates that the combination of dalantercept plus axitinib is overall well tolerated with a generally non-overlapping safety profile in patients with previously treated RCC,' wrote researcher Martin H. Voss...'While it is not possible to say to what extent these findings reflect antitumor effect of axitinib vs the combination, these outcomes compare favorably to the historical ORR of 11% and median progression-free survival of 4.8 months reported for axitinib in patients pretreated with sunitinib,' the researchers wrote."

Online posting

Dalantercept in Treating Patients With Recurrent Ovarian Epithelial, Fallopian Tube, or Primary Peritoneal Cavity Cancer (clinicaltrials.gov) - P2; N=30; Active, not recruiting; Sponsor: Gynecologic Oncology Group; N=56 ➔ 30

Enrollment change • Biosimilar • Gynecologic Cancers • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Ovarian Cancer • Solid Tumor

Phase II randomized study of dalantercept in combination with axitinib compared to axitinib alone as second-line treatment in patients with metastatic renal cell carcinoma (ASCO 2013) - Presentation time: Monday, Jun 3, 8:00 AM - 11:45 AM; Abstract #TPS4595; P2, N=156; NCT01727336; Sponsor: Acceleron; "The primary efficacy endpoint is PFS. Secondary endpoints are OS, TTP, ORR, DOR, DCR, and PD biomarkers on archived tumor and serum specimens including BMP9/10 and ALK1 expression"

Clinical protocol • Renal Cell Carcinoma

Novel combination 'encouraging' in advanced kidney cancer (Medscape) - P2, N=29; NCT01727336; "The preliminary median progression-free survival of 8.3 months in all dose levels combined is encouraging....Another key finding from this small phase 2 randomized trial (n = 29) was the objective response rate of 25.0% (7 partial responses of 28 patients), and stable disease was observed in 17 of 28 patients (60.7%). The disease control rate at 6 months was 57.1% (16 of 28 patients)."

P2 data • Oncology • Renal Cell Carcinoma

A phase 2, randomized trial evaluating the combination of dalantercept plus axitinib in patients with advanced clear cell renal cell carcinoma. (PubMed, Cancer) - "Although well tolerated, the addition of dalantercept to axitinib did not appear to improve treatment-related outcomes in previously treated patients with advanced RCC."

Clinical • Journal • P2 data • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Urothelial Cancer

A Phase Ib, Open-Label Study of Dalantercept, an Activin Receptor-Like Kinase 1 Ligand Trap, plus Sorafenib in Advanced Hepatocellular Carcinoma. (PubMed, Oncologist) - "The addition of dalantercept to sorafenib did not improve antitumor activity in patients with HCC. The dalantercept program in this population was discontinued."

Biomarker • Clinical • Journal

A phase II evaluation of dalantercept, a novel soluble recombinant activin receptor-like kinase 1 (ALK-1) inhibitor receptor-fusion protein, in the treatment of persistent or recurrent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma (NRG-USA 2019) - No abstract available.

P2 data

A phase II evaluation of dalantercept, a novel soluble recombinant activin receptor-like kinase 1 (ALK-1) inhibitor receptor-fusion protein, in the treatment of persistent or recurrent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma (R Burger) Gynecol Oncol 2018 (NRG-USA 2019) - No abstract available.

P2 data

NRG Oncology Semiannual Meeting - "Friday, February 8, 2019, 8:05 – 8:17 am, NRG Oncology Phase II Randomized Trial of nivolumab with or without Ipilimumab in patients with persistent or recurrent ovarian cancer; Saturday, February 9, 2019, 8: 45 AM - 9:00 AM, Active Phase I Studies (including safety lead-ins): NRG-GY007 A phase I/II study of ruxolitinib with front-line neoadjuvant and post-surgical therapy in patients with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer; 170R A phase II evaluation of dalantercept, a novel soluble recombinant activin receptor-like kinase 1 (ALK-1) inhibitor receptorfusion protein, in the treatment of persistent or recurrent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma; February 9, 2019, 10:00 AM – 12:00 PM, NRG-GY007; February 8-9, 2019, 8:00 am - 10:00 am, GOG0218 A Phase III trial of carboplatin and paclitaxel...primary peritoneal or fallopian tube cancer; Review of Active Studies: NRG-GY007; Activated for Phase I..."

CME

Study of Dalantercept and Axitinib in Patients With Advanced Renal Cell Carcinoma (clinicaltrials.gov) - P2; N=131; Completed; Sponsor: Acceleron Pharma, Inc.; Active, not recruiting ➔ Completed; Trial completion date: Dec 2018 ➔ Nov 2017; Trial primary completion date: Jun 2018 ➔ Jun 2017

Clinical • Trial completion • Trial completion date • Trial primary completion date