eflornithine / Orbus Therap - LARVOL DELTA

Orbus Therapeutics Announces Publication of Phase 3 STELLAR Clinical Study Results Showing Clinically Meaningful Improvements in Rare Brain Tumor in Journal of Clinical Oncology (JCO) (GlobeNewswire) - "In the 196 patients with recurrent grade 3 IDH mutant astrocytoma subset, clinically meaningful improvements in both OS and PFS were observed; Median OS in the eflornithine + lomustine arm was 34.9 months compared to 23.5 months in the lomustine alone arm with HR = 0.64 (log rank p = 0.01); PFS showed a correlating benefit with median PFS of 15.8 months in the eflornithine + lomustine arm and 7.2 months in the lomustine alone arm with HR = 0.57 (log rank p = 0.01); The combination of eflornithine + lomustine was generally well-tolerated. The known side effect profile of eflornithine combined with lomustine was consistent with data from earlier studies and no new safety signals were identified."

P3 data • Astrocytoma

Updated results of Phase 3 STELLAR trial: Eflornithine improves overall survival and blinded independent central review determined progression free survival in patients with recurrent WHO 2021 grade 3 IDH-mutant astrocytoma (SNO 2025) - "BACKGROUND: STELLAR was a phase III randomized, open-label trial of eflornithine (ornithine decarboxylase inhibitor) with lomustine versus lomustine alone in patients with recurrent anaplastic astrocytoma (AA). The clinically meaningful OS and PFS benefits observed with eflornithine in the molecularly defined 2021 WHO CNS grade 3 astrocytomas is further confirmed and expanded based on additional molecular classification and BICR of PFS."

Clinical • P3 data • Review • Anaplastic Astrocytoma • Astrocytoma • Brain Cancer • Glioblastoma • Oncology • Solid Tumor • CDKN2A • CDKN2B

Orbus Therapeutics Highlights Phase 3 STELLAR Clinical Study Results Showing Clinically Meaningful Benefits in Rare Brain Tumor at Society for Neuro-Oncology (SNO) Annual Meeting (GlobeNewswire) - "The study enrolled a total of 343 patients who were stratified by key characteristics, including IDH mutation status....In the 196 patients with recurrent grade 3 IDH mutant astrocytoma, clinically meaningful improvements in both OS and PFS were observed. Median OS in the eflornithine + lomustine arm was 34.9 months compared to 23.5 months in the lomustine alone arm with HR = 0.64 (log rank p = 0.01). Physician determined PFS, as previously reported, showed a correlating benefit with median PFS of 15.8 months in the eflornithine + lomustine arm and 7.2 months in the lomustine alone arm with HR = 0.57 (log rank p = 0.01)."

P3 data • Astrocytoma

Updated results of Phase 3 STELLAR trial: Eflornithine improves overall survival and blinded independent central review determined progression free survival in patients with recurrent WHO 2021 grade 3 IDH-mutant astrocytoma (WFNOS 2025) - "BACKGROUND: STELLAR was a phase III randomized, open-label trial of eflornithine (ornithine decarboxylase inhibitor) with lomustine versus lomustine alone in patients with recurrent anaplastic astrocytoma (AA). The clinically meaningful OS and PFS benefits observed with eflornithine in the molecularly defined 2021 WHO CNS grade 3 astrocytomas is further confirmed and expanded based on additional molecular classification and BICR of PFS."

Clinical • P3 data • Review • Anaplastic Astrocytoma • Astrocytoma • Brain Cancer • Glioblastoma • Oncology • Solid Tumor • CDKN2A • CDKN2B

Orbus Therapeutics Announces Oral Presentation of Updated Results With Blinded Independent Central Review from the Phase 3 STELLAR Clinical Trial at the Society for Neuro-Oncology Annual Meeting (GlobeNewswire)

P3 data • Astrocytoma

Evaluation of Eflornithine Plus Temozolomide in Patients With Newly Diagnosed Glioblastoma or Astrocytoma (clinicaltrials.gov) - P1 | N=66 | Recruiting | Sponsor: Orbus Therapeutics, Inc. | Trial completion date: Dec 2024 ➔ Jun 2026 | Trial primary completion date: Dec 2024 ➔ Jun 2026

Trial completion date • Trial primary completion date • Astrocytoma • Brain Cancer • Glioblastoma • Oncology • Solid Tumor

PHASE 3 STELLAR STUDY SHOWS EFLORNITHINE IMPROVES OVERALL SURVIVAL (OS) AND PROGRESSION FREE SURVIVAL (PFS) IN PATIENTS WITH RECURRENT 2021 WHO ASTROCYTOMA, IDH-MUTANT GRADE 3 (SNO 2024) - "STELLAR was a phase III randomized, open-label trial of eflornithine (ornithine decarboxylase inhibitor) with lomustine versus lomustine alone, originally for patients with recurrent AA. However, as the WHO definition of AA evolved during trial conduct (e.g., excluding IDH wild-type disease), we determined results in both the original ITT population and by revised molecularly defined WHO 2021 diagnoses in pre-planned analyses .METHOD Key eligibility: age ≥ 18, AA (2016 WHO criteria), first recurrence ≥ 6 months after radiation and temozolomide, KPS ≥ 70, no imaging findings consistent with grade 4 glioblastoma...CONCLUSION There was no difference in OS between arms in the ITT analysis. However, medically meaningful and statistically significant OS and PFS benefits were observed with eflornithine in the pre-planned analysis of patients with molecularly defined 2021 WHO CNS grade 3 astrocytoma."

Clinical • Late-breaking abstract • P3 data • Anaplastic Astrocytoma • Astrocytoma • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

Combination of Eflornithine and Lomustine Demonstrates Clinically Meaningful Improvements in Overall Survival (OS) and Progression Free Survival (PFS) in Patients with Recurrent Astrocytoma, IDH Mutant Grade 3 (GlobeNewswire) - P3 | N=343 | STELLAR (NCT02796261) | Sponsor: Orbus Therapeutics, Inc. | "The primary efficacy endpoint, overall survival (OS) in the intention-to-treat population of 343 patients had a hazard ratio (HR) = 0.94 and was not statistically significant; In the 194 patients with recurrent grade 3 IDH mutant astrocytoma, clinically meaningful improvements in both OS and PFS were observed; Median OS in the eflornithine + lomustine arm was 34.9 months compared to 23.5 months in the lomustine alone arm with HR = 0.64 (log rank p = 0.016); PFS showed a correlating benefit with median PFS of 15.8 months in the eflornithine + lomustine arm and 7.2 months in the lomustine alone arm with HR = 0.58 (log rank p = 0.015); The combination of eflornithine and lomustine was generally well-tolerated....The results from the Phase 3 STELLAR study will be presented at an upcoming medical conference."

P3 data • Astrocytoma • Oncology • Solid Tumor

Evaluation of Eflornithine Plus Temozolomide in Patients With Newly Diagnosed Glioblastoma (clinicaltrials.gov) - P1 | N=66 | Recruiting | Sponsor: Orbus Therapeutics, Inc. | Phase classification: P1b ➔ P1

Phase classification • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

Amgen and US WorldMeds: A Tale of Data and Two FDA Adcomm Meetings (BioSpace) - "Despite the lack of a randomized controlled trial for US WorldMeds’ investigational drug, the FDA’s Oncologic Drugs Advisory Committee in a potentially precedent-setting decision found that the company provided adequate data to support its benefit in high-risk neuroblastoma. In a 14-6 vote, the adcomm determined that US WorldMeds provided enough evidence from a Phase II study to conclude that eflornithine hydrochloride (DFMO) boosts event-free survival in its target pediatric patient population."

ODAC • Neuroblastoma

Orbus Therapeutics Announces First Patient Enrolled in Phase 1 Clinical Study in Newly Diagnosed Glioblastoma (GlobeNewswire) - "Orbus Therapeutics Inc...announced today that the first patient has been enrolled in its Phase 1b study combining temozolomide and eflornithine in patients newly diagnosed with glioblastoma....The Phase 1b study is an open-label, single arm, dose-limiting toxicity clinical trial that will include approximately 8 leading neuro-oncology clinical trial centers in the United States."

Trial status • CNS Tumor • Glioblastoma • Glioma • Oncology

Evaluation of Eflornithine Plus Temozolomide in Patients With Newly Diagnosed Glioblastoma (clinicaltrials.gov) - P1b | N=60 | Recruiting | Sponsor: Orbus Therapeutics, Inc.

New P1 trial • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

STELLAR: Study to Evaluate Eflornithine + Lomustine vs Lomustine in Recurrent Anaplastic Astrocytoma (AA) Patients (clinicaltrials.gov) - P3; N=343; Active, not recruiting; Sponsor: Orbus Therapeutics, Inc.; Trial completion date: Dec 2022 ➔ Jun 2023; Trial primary completion date: Dec 2022 ➔ Jun 2023

Trial completion date • Trial primary completion date • Anaplastic Astrocytoma • Astrocytoma • Brain Cancer • Oncology • Solid Tumor • MRI

Orbus Therapeutics’ Phase 3 Eflornithine STELLAR Study Reaches Full Patient Enrollment (GlobeNewswire) - "Orbus Therapeutics Inc...announced that patient enrollment of its Phase 3 STELLAR clinical study of eflornithine in patients with recurrent anaplastic astrocytoma is complete. The STELLAR study completed full enrollment with a total of 343 patients....'We look forward to conducting an interim analysis for superiority in 2022.'"

Enrollment closed • P3 data • Anaplastic Astrocytoma • Astrocytoma • CNS Tumor • Oncology • Solid Tumor

STELLAR: Study to Evaluate Eflornithine + Lomustine vs Lomustine in Recurrent Anaplastic Astrocytoma (AA) Patients (clinicaltrials.gov) - P3; N=343; Active, not recruiting; Sponsor: Orbus Therapeutics, Inc.; Recruiting ➔ Active, not recruiting; Trial completion date: Dec 2021 ➔ Dec 2022; Trial primary completion date: Dec 2021 ➔ Dec 2022

Clinical • Enrollment closed • Trial completion date • Trial primary completion date • Anaplastic Astrocytoma • Astrocytoma • Brain Cancer • Oncology • Solid Tumor • MRI

Orbus Therapeutics Granted European Patent for Method of Use for Eflornithine (GlobeNewswire) - "Orbus Therapeutics Inc., a private, late-stage biopharmaceutical company focused on the development and commercialization of therapies that treat rare diseases, announced that it has been granted patent No. 3432872 entitled 'Compositions and Methods for Use of Eflornithine and Derivatives and Analogs thereof to Treat Cancers, Including Gliomas,' by the European Patent Office (EPO)."

Patent • Brain Cancer • Glioma • Oncology

Orbus Therapeutics Announces Positive Outcome of Pre-Planned Interim Futility Analysis for Phase 3 Eflornithine STELLAR Study (GlobeNewswire) - "Orbus Therapeutics Inc...today announced a positive outcome of the pre-planned interim analysis for futility in its Phase 3 STELLAR clinical study of eflornithine in patients with recurrent anaplastic astrocytoma...For this pre-planned interim analysis for futility, the IDMC’s recommendation to continue the study was to be based upon the hazard ratio in the STELLAR study being less than one. Based on its review of the efficacy and safety data, the IDMC recommended that the STELLAR study proceed without any modifications...We expect to complete full enrollment of patients in the STELLAR study in the second half of 2021, and our next pre-planned interim analysis, which will test superiority, is expected to occur in 2022."

DSMB • Enrollment status • Anaplastic Astrocytoma • Astrocytoma • Oncology

STELLAR: Study to Evaluate Eflornithine + Lomustine vs Lomustine in Recurrent Anaplastic Astrocytoma (AA) Patients (clinicaltrials.gov) - P3; N=340; Recruiting; Sponsor: Orbus Therapeutics, Inc.; Trial completion date: Jun 2020 ➔ Dec 2021; Trial primary completion date: Jun 2020 ➔ Dec 2021

Clinical • Trial completion date • Trial primary completion date • Anaplastic Astrocytoma • Astrocytoma • Brain Cancer • Oncology • Solid Tumor

Eflornithine plus Sulindac for Prevention of Progression in Familial Adenomatous Polyposis. (PubMed, N Engl J Med) - P3 | "In this trial involving patients with familial adenomatous polyposis, the incidence of disease progression was not significantly lower with the combination of eflornithine and sulindac than with either drug alone. (Funded by Cancer Prevention Pharmaceuticals; ClinicalTrials.gov number, NCT01483144; EudraCT number, 2012-000427-41.)."

Journal • P3 data • Gastrointestinal Disorder • Oncology

Assessment of the skin efficacy and acceptability of a cosmetic product in the treatment of the forearm hypertrichosis in female patients. (PubMed, J Cosmet Dermatol) - "The study shows that a cosmetic formulation based on capryloyl glycine 4% is highly effective in reducing several parameters related to hair growth and hair thickness vs placebo, thus showing efficacy in the treatment of hypertrichosis."

Clinical • Journal • Aesthetic Medicine • Dermatology

Orbus Therapeutics Receives U.S. Patent for Eflornithine Formulations (GlobeNewswire) - "Orbus Therapeutics Inc...announced that it has been granted patent No. 10,786,470 entitled “Formulations for Administration of Eflornithine,” by the United States Patent and Trademark Office (USPTO)."

Patent • Brain Cancer • Oncology

Study of DFMO in Combination With Bortezomib for Relapsed or Refractory Neuroblastoma (clinicaltrials.gov) - P1/2; N=16; Active, not recruiting; Sponsor: Giselle SaulnierSholler; Trial completion date: Dec 2020 ➔ Dec 2021; Trial primary completion date: Dec 2020 ➔ Dec 2021

Clinical • Combination therapy • Trial completion date • Trial primary completion date • Neuroblastoma • Oncology • Solid Tumor

Effect of eflornithine on mutation frequency in temozolomide-treated U87MG cells. (PubMed, Oncotarget) - "The current chemotherapy options include nitrosoureas (e.g., lomustine) and the imidazotetrazine-class monofunctional DNA alkylating agent, temozolomide (TMZ). It was shown that TMZ significantly increased the frequency of mutations in U87MG glioblastoma cells while DFMO-treated cells showed mutation frequency statistically similar to that of the untreated cells on the respective treatment days. The findings of this study provide evidence to support the hypothesis that DFMO may inhibit progression of DNA mutations caused by alkylating chemotherapy agents, such as TMZ."

Journal • Glioblastoma • Glioma • Oncology • Solid Tumor

Irinotecan Hydrochloride, Temozolomide, and Dinutuximab With or Without Eflornithine in Treating Patients With Relapsed or Refractory Neuroblastoma (clinicaltrials.gov) - P2; N=95; Recruiting; Sponsor: Children's Oncology Group; Suspended ➔ Recruiting

Clinical • Enrollment open • Ganglioneuroblastoma • Neuroblastoma • Oncology • Solid Tumor

[VIRTUAL] Sulindac and Eflornithine Combination Delays the Need for Lower Gastrointestinal Surgery in Familial Adenomatous Polyposis: CPP FAP-310 Trial (ACG 2020) - "A total of 158 patients in the CPP FAP-310 trial fit the criteria for this LGI disease progression assessment. FAP disease progression was observed in 2/54 (3.7%), 9/53 (17.0%), and 10/51 (19.6%) patients in the combination, sulindac, and eflornithine arms, respectively, corresponding to risk reductions of 80% (hazard ratio [HR]=0.20; 95% CI: 0.05-0.80; p=0.02) and 83% (HR=0.17; 95%CI: 0.04-0.70; p=0.01) between combination and sulindac alone or eflornithine alone, respectively (Figure). The need for surgery as determined by the endoscopist occurred in 0, 7 (13.2%), and 8 (15.7%) patients in the combination, sulindac, and eflornithine arms, respectively, corresponding to risk reductions approaching 100% both between the combination and sulindac arms (HR=0.00; 95%CI: 0.00-0.48; p=0.005) and between the combination and eflornithine arms (HR=0.00; 95%CI: 0.00-0.44; p=0.003)."

Colonic Polyps • Gastrointestinal Disorder