FDA Grants Orphan Drug Designation to Sotigalimab for Soft Tissue Sarcoma

The FDA has granted an orphan drug designation to sotigalimab as a potential therapeutic option for patients with soft tissue sarcoma.

The FDA has granted an orphan drug designation to sotigalimab (APX005M) as a potential therapeutic option for patients with soft tissue sarcoma, according to announcement from Apexigen Inc., the drug developer.1

A novel, humanized monoclonal antibody, sotigalimab was designed stimulate antitumor immune response and to target CD40, which is a key co-stimulatory receptor that serves to activate innate and adaptive immune systems. When sotigalimab binds to CD40 on antigen-presenting cells, it induces a multifaceted immune response that brings several components of the immune system together to attack the cancer.

The safety and efficacy of the agent in combination with standard-of-care doxorubicin is being evaluated in patients with advanced soft tissue sarcomas as part of a phase 2 clinical trial (NCT03719430) that is estimated to enroll a total of 27 participants.2

“We are pleased to receive orphan drug designation for sotigalimab, an important step toward addressing the medical need that exists for patients with sarcoma,” Xiaodong Yang, MD, PhD, president, and chief executive officer of Apexigen, Inc., stated in a press release. “There are currently limited treatment options available for patients with soft tissue sarcoma, so we are excited by the emerging data from our ongoing phase 2 study in this indication, coupled with data across our broad clinical development program, that suggest sotigalimab may provide superior clinical benefit.”

To be eligible for enrollment to the phase 2 trial, patients must have histologically confirmed advanced soft tissue sarcoma, measurable disease that is locally advanced and unresectable or metastatic, an ECOG performance status of 0 to 1, normal left ventricular systolic function, and acceptable laboratory parameters.

Patients could not have received prior chemotherapy, immunotherapy, radiotherapy, or another investigational agent for a malignancy within the 21 days before study registration. Patients also could not have previously received anthracycline chemotherapy or a CD40 agonist, nor could they have received whole pelvis radiation or radiotherapy of the mediastinal or pericardial area.

The primary objective of the trial is objective response rate, and key secondary objectives include determining the recommended dose for the combination, evaluating the adverse effects (AEs) that occur with the regimen, and examining progression-free survival. Investigators will also evaluate changes in immune cell infiltrates in baseline and on-study biopsies and the expression of CD40 in baseline biopsies.

Previously, the agent was evaluated in combination with chemotherapy and with or without nivolumab (Opdivo) in the treatment of patients with metastatic pancreatic adenocarcinoma, as part of a phase 1b trial (NCT03214250).3

The non-randomized trial enrolled patients who were 18 years of age with untreated metastatic pancreatic adenocarcinoma, an ECOG performance status of 0 to 1, and measurable disease per RECIST v1.1 criteria.

Study participants received intravenous gemcitabine at a dose of 1000 mg/m2 and intravenous nab-paclitaxel (Abraxane) at a dose of 125 mg/m2. Participants in cohorts B1 and C1 received intravenous sotigalimab at 0.1 mg/kg; those in cohorts B2 and C2 received the agent at 0.3 mg/kg. Those in cohorts C1 and C2 also receied intravenous nivolumab at a dose of 240 mg.

The primary end points of the trial were incidence of AEs in all participants who were given at least 1 dose of any study drug, incidence of dose-limiting toxicities (DLT) in all who experienced a DLT or received at least 2 doses of gemcitabine plus nab-paclitaxel and 1 dose of sotigalimab during cycle 1, and to establish the recommended phase 2 dose (RP2D) of sotigalimab.

A total of 42 patients underwent screening between August 22, 2017, and July 10, 2018; of these patients, 30 were enrolled to the trial and received at least 1 dose of a study drug.

Twenty-four patients were determined to be evaluable for DLTs at a median follow-up of 17.8 months (range, 16.0-19.4). Responses were experienced by 58% of 24 DLT-evaluable patients; this included 4 patients in cohort B1, 4 in cohort C1, 4 in cohort C2, and 2 in cohort B2.

Two DLTs were experienced by 2 patients in cohorts B2 and C1; these effects were both febrile neutropenia and they were grade 3 and grade 4, respectively. The most common grade 3 or 4 treatment-related AEs included decreased lymphocyte count (67%), anemia (37%), and decreased neutrophil count (30%). Of the 30 patients, 47% had a treatment-related serious AE. The serious AE that was reported most frequently was pyrexia (20%). Two chemotherapy-related deaths because of AEs were reported; 1 patient in cohort B1 had sepsis and 1 patient in cohort C1 had septic shock.

The RP2D for sotigalimab was established to be 0.3 mg/kg.

Sotigalimab is also being evaluated in phase 2 clinical trials as a potential therapeutic option for patients with esophageal and gastroesophageal junction cancers, melanoma, rectal cancer, and sarcoma in multiple combinations with immunotherapy, chemotherapy, radiation therapy, or a cancer vaccine.


  1. Apexigen receives orphan drug designation from the FDA for sotigalimab (APX005M) for the treatment of soft tissue sarcoma. News release. Apexigen, Inc. August 5, 2021. Accessed August 5, 2021. https://bit.ly/2Vwx3lY
  2. APX005M and doxorubicin in advanced sarcoma. ClinicalTrials.gov. Updated April 19, 2021. Accessed August 5, 2021. https://clinicaltrials.gov/ct2/show/NCT03719430
  3. O’Hara MH, O’Reilly EM, Varadhachary G, et al. CD40 agonistic monoclonal antibody APX005M (sotigalimab) and chemotherapy, with or without nivolumab, for the treatment of metastatic pancreatic adenocarcinoma: an open-label, multicentre, phase 1b study. Lancet Oncol. 2021;22(1):118-131. doi:10.1016/S1470-2045(20)30532-5