Novel Agent Shows Early Activity in Phase 2 Recurrent Thymoma Study

Investigators of the phase 2 trial (NCT05104736) are assessing PT-112 in patients with thymoma and thymic carcinoma.

PT-112, a novel small molecule inhibitor of ribosome biogenesis, fulfilled the pre-specified efficacy requirement of a phase 2 trial (NCT05104736) assessing the agent among a small cohort of patients with recurrent thymoma, according to a press release from the developer, Promontory Therapeutics Inc.1

Among 10 patients who were evaluable for tumor response, partial responses (PRs) occurred in 3 (30%). The reported objective response rate (ORR) appeared to numerically surpass that of recent phase 2 monotherapy data in the public domain related to current off-label therapies.

Investigators reported that treatment with PT-112 was well-tolerated, as there were no new safety signals. Patients who received PT-112 at the recommended phase 3 dose experienced enduring disease control without symptomatic toxicities, and no patients discontinued treatment due to toxicity.

Enrollment of patients with recurrent thymoma in the phase 2 trial remains ongoing at the National Cancer Institute.

According to the press release, those with recurrent thymoma have limited standard-of-care treatment options; there are no currently approved regimens for this disease in the US, EU, or Japan. Patients with recurrent thymoma may experience a risk of paraneoplastic autoimmune diseases, which consequently raises the possibility of immune-related adverse effects (IRAEs) that can occur during T-cell therapy. With early observations pointing towards a lack of increased new-onset IRAEs in patients who receive PT-112, developers believe the agent may offer a new immunomodulatory therapy that does not heighten the risk of immune toxicity.

Investigators of the phase 2 trial are assessing PT-112 in patients with thymoma and thymic carcinoma.2 The study investigators noted that PT-112, an investigational metallo-pyrophosphate conjugate, may provide a unique set of properties related to cellular interaction and molecular antitumor mechanisms, which include resistance towards DNA repair pathways and facilitation of immunogenic cell death.

Patients will receive PT-112 intravenously in 28-day cycles, including 360 mg/m2 on days 1 and 15 in cycle 1 and 250 mg/m2 on day 1 of each subsequent cycle until progressive disease, intolerable AEs, or a maximum of 8 years.

The trial’s primary end point is ORR per RECIST v1.1 criteria. Secondary end points include overall survival, progression-free survival, duration of response, and safety.

Patients 18 years and older with histologically confirmed thymoma or thymic carcinoma, at least 1 prior line of platinum-based chemotherapy, and measurable disease based on 1 or more measurable lesions per RECIST v1.1 guidelines are eligible for enrollment on the trial. Other eligibility criteria include having an ECOG performance status of 0 or 1 and adequate organ and marrow function. Those with previously treated brain or central nervous system metastases are eligible for enrollment if they have recovered from any acute toxicities associated with radiotherapy and do not require treatment with steroids.

Those with concurrent treatment with a non-permitted agent or major surgery within 14 days of enrollment are ineligible for study entry. Patients are also unable to enroll if they have active infection requiring systemic therapy, significant acute or chronic infections, use of hormonal agents as anti-cancer therapy within 14 days of enrollment, or uncontrolled intercurrent illness.

Data presented at the 2025 American Association for Cancer Research Annual Meeting (AACR) showed that among the first 15 patients with thymic epithelial tumors, PT-112 monotherapy correlated with significant increases in CD8- and CD4-positive cells as well as natural killer cells.3

“In line with prior non-clinical and clinical findings, data from these ongoing phase 2 trials show that PT-112 induces robust signals of immune activation and [immunogenic cell death] across the adaptive and innate immune systems and are indicative that PT-112’s immune effects play a significant role in its anti-cancer mechanism,” Arun Rajan, MD, of the National Cancer Institute in Bethesda, Maryland, wrote with coauthors.3

References

1. Promontory Therapeutics announces interim efficacy requirement reached on phase 2 study of PT-112 monotherapy in patients with recurrent thymoma. News release. Promontory Therapeutics Inc. December 22, 2025. Accessed December 22, 2025. https://tinyurl.com/ytshpd9b
2. PT-112 in subjects with thymoma and thymic carcinoma. ClinicalTrials.gov. Updated September 19, 2025. Accessed December 22, 2025. https://tinyurl.com/2se2tm9k
3. Rajan A, Ames TD, Celades-Errando C, et al. Anti-cancer immune effects of PT-112 monotherapy across two disease indications. Abstract presented at: 2025 American Association for Cancer Research Annual Meeting; April 25-30, 2025; Chicago, IL. Abstract 5819.