Cure Alveolar Soft Part Sarcoma International (iCureASPS)

Multi-Arm Study to Test the Efficacy of Immunotherapeutic Agents in Multiple Sarcoma Subtypes
NCT02815995
https://clinicaltrials.gov/ct2/show/NCT02815995
Durvalumab and Tremelimumab
Durvalumab[1] is an FDA-approved immunotherapy for cancer, developed by Medimmune/AstraZeneca.[2] It is a human immunoglobulin G1 kappa (IgG1κ) monoclonal antibody that blocks the interaction of programmed cell death ligand 1 (PD-L1) with the PD-1 and CD80 (B7.1) molecules.

Tremelimumab (formerly ticilimumab, CP-675,206) is a fully human monoclonal antibody against CTLA-4. It is an immune checkpoint blocker. Previously in development by Pfizer,[1] it is now in investigation by MedImmune, a wholly owned subsidiary of AstraZeneca.Tremelimumab aims to stimulate an immune system attack on tumors.

We just learned that this trial is now open for more ASPS patients. They had previously close the trial for ASPS patients because only two were allowed of one type, but since both patients responses have been positive, the Sarcoma team at MD Anderson is now looking for more ASPS patients!
the name of the trial:
Multi-Arm Study to Test the Efficacy of Immunotherapeutic Agents in Multiple Sarcoma Subtypes
NCT02815995
https://clinicaltrials.gov/ct2/show/NCT02815995
there is a contact info in the link above.

There are two drugs combo tested - one targets (PD-L1) with the PD-1 and CD80 (B7.1) molecules and the other targets CTLA-4.

Ivan has received a PM today so I decided to post it FYI -
"I am an investigator at MD Anderson and wanted to make this community aware of our ongoing trial with durvalumab and tremelimumab that is open to ASPS patients with positive results so far. ClinicalTrials.gov Identifier: NCT02815995."
so they are actively enrolling ASPS patients, if you have no other options, you can apply incl. international patients.

Response to Immune Checkpoint Inhibition in Two Patients with Alveolar Soft-Part Sarcoma.
This is in Canada :)

Citation
Cancer Immunol Res. 2018 Sep;6(9):1001-1007. doi: 10.1158/2326-6066.CIR-18-0037. Epub 2018 Jul 17.


Abstract
Alveolar soft-part sarcoma (ASPS) is a morphologically distinctive mesenchymal tumor characterized by a canonical ASPL-TFE3 fusion product. In the metastatic setting, standard cytotoxic chemotherapies are typically ineffective. Studies have suggested modest clinical response to multitargeted receptor tyrosine kinase inhibitors. Here, we report sustained partial responses in two patients with immune checkpoint inhibition treated with either durvalumab (anti-PD-L1) alone or in combination with tremelimumab (anti-CTLA-4), which appeared unrelated to tumor immune infiltrates or mutational burden. Genomic analysis of these patients, and other cases of ASPS, demonstrated molecular mismatch-repair deficiency signatures. These findings suggest that immune checkpoint blockade may be a useful therapeutic strategy for ASPS. Cancer Immunol Res; 6(9); 1001-7.

https://www.ncbi.nlm.nih.gov/m/pubmed/30018044/

Response to Immune Checkpoint Inhibition in Two Patients with Alveolar Soft-Part Sarcoma


Results

Case histories of two patients on immunotherapy

Patient 1 was a 22-year-old female who in 2014 identified a growing lesion on her dorsal left hand. Imaging revealed a destructive lesion in the 4th/5th metacarpals and the presence of multifocal pulmonary metastases. Biopsy demonstrated a neoplasm composed of polygonal cells with a nested architecture. IHC was positive for TFE3, and molecular testing confirmed the presence of the ASPSCR1–TFE3 fusion product, consistent with ASPS. The patient was treated with a multikinase inhibitor against Aurora A, VEGFRs, and FGFRs (April 2014–July 2014) with progression at the primary site. Subsequently, preoperative radiation was delivered followed by palliative ray amputation. Upon pulmonary progression, between December 2014 and May 2015, she was treated sequentially without benefit on trials with an OX40 agonist and then a NOTCH inhibitor. After further progression, the patient was treated within the D4190C00010 trial, which investigates the combination of durvalumab and tremelimumab (NCT02261220). Treatment was started on June 18, 2015. On October 5, 2015, CT images demonstrated 30% reduction in the sum of target lesions as per Response Evaluation Criteria in Solid Tumors (RECIST; Fig. 1). After 4 cycles of combination treatment, the patient was admitted with an immune-related (irAE) grade 4 diarrhea requiring treatment with intravenous methylprednisolone. A colonoscopy demonstrated features of colitis requiring a 4-month prednisolone taper and drug hold from August 2015 until March 2016. Despite being off therapy for 8 months, the patient continued to have ongoing response in her target lesions with tumor reduction of 53% on March 10, 2016. Given the absence of residual irAE, the patient was retreated with durvalumab from March 22, 2016, until May 31, 2016, completing the treatment as per protocol. On the last follow-up in January 2018, continual response was demonstrated with 73% tumor reduction despite being off therapy for >18 months.