SY-5609 Receives Orphan Drug Designation From FDA in Relapsed Metastatic Pancreatic Cancer

An ongoing phase 1 trial is assessing the potential of SY-5609 plus chemotherapy in patients with advanced solid tumors, with the FDA granting orphan drug designation to the combination for patients with relapsed metastatic pancreatic cancer.

The FDA has granted orphan drug designation to SY-5609, a CDK7 inhibitor, in combination with chemotherapy for patients with relapsed metastatic pancreatic cancer, according to a press release from Syros Pharmaceuticals.

An ongoing phase 1 trial (NCT04247126) is underway investigating SY-5609 plus chemotherapy in patients who have progressed on leucovorin calcium, fluorouracil, irinotecan hydrochloride, and oxaliplatin (FOLFIRINIX). Other tumors being investigated in this trial include advanced solid tumors, breast cancer, and small cell lung cancer. The study’s safety and clinical activity data are set to read out in second half of 2022.

“This orphan drug designation underscores the urgency of our efforts to develop SY-5609 for patients with pancreatic cancer, one of the most devastating and difficult to treat malignancies,” David A. Roth, MD, chief medical officer at Syros, said in the press release. “Based on the early data we reported last year, which demonstrated single-agent activity in heavily pre-treated patients, as well as compelling preclinical data and a strong mechanistic rationale, we believe SY-5609 could deliver meaningful benefit to people with pancreatic cancer, whose tumors have otherwise eluded therapeutic intervention. We look forward to sharing initial data from the safety lead-in portion of our ongoing phase 1 study later this year.”

A total of 160 patients are estimated to be enrolled in the trial. Those who participate will be randomly assigned to receive either SY-5609 plus gemcitabine and nab-paclitaxel at approved doses. The study aims to measure efficacy such as disease control rate, progression-free survival, and safety. The treatment arms included SY-5609 monotherapy (group 1), SY-5609 plus fulvestrant (group 2), SY-5609 plus gemcitabine (group 3), and SY-5609 plus gemcitabine and nab-paclitaxel (group 4).

The primary end points include dose-limiting toxicities of SY-5609 in groups 1 and 2 and the number of participants with treatment-emergent adverse effects (TEAEs). In groups 3 and 4, the primary end points are dose-limiting toxicities and TEAEs along with progression-free survival (PFS). Secondary end points included area under the concentration vs time curve of SY-5609, apparent clearance of SY-5609, apparent volume distribution, PFS, objective response rate, and complete response rate.

Patients were included in the trial if they had advanced solid tumors for which standard curative or palliative measures do not exist or are no longer effective. Other inclusion criteria included patients who are post-menopausal with hormone receptor–positive, HER2-negative advanced or metastatic breast cancer, and those with histologically or cytologically confirmed pancreatic adenocarcinoma. Patients must also have 1 measurable lesion, have had prior toxicities resolved, and adequate bone and marrow function.

Patients were excluded from the study if they had chemotherapy or limited field radiotherapy within 2 weeks, wide field radiotherapy within 4 weeks, or nitrosoureas or mitomycin C within 6 weeks prior to the study. If patients received major surgery within 2 weeks of treatment, prior investigational treatments within 4 weeks, and noncytotoxic FDA-approved anticancer therapy within 2 previous weeks, they were excluded from enrollment.


Syros receives FDA orphan drug designation for SY-5609 for the treatment of pancreatic cancer. News Release. Syros. September 13, 2022. Accessed September 19, 2022.