Introduction/Background Recurrent disease after secondary cytoreductive surgery for ovarian cancer (OC) is frequent. Radspherin is a novel alpha-emitting therapy. Alpha particles have high linear energy transfer and a radiation range < 100 µm (3–10 cell diameters), generating highly effective radiation with non-repairable double-strand DNA breaks in affected cells, killing micrometastasis and free-floating tumour cells after surgical resection, and reduced risk of toxicity compared with beta or gamma radiation.
Methodology Here we report on the phase 1 study (NCT03732768) evaluating the recommended dose and safety of Radspherin in patients with a secondary R0 resection of platinum-sensitive recurrent epithelial OC. Radspherin is injected intraperitoneally two days after surgery. Dose escalation was performed at 1–2-4–7-MBq. Safety interim analysis after completion of the dose-limiting toxicity (DLT) period is presented here.
Results 14 patients were enrolled in the dose escalation cohort. Median age was 66 (56–77). Median peritoneal cancer index was 7 (3–16). The 7MBq dose was selected as recommended dose as no DLT was observed. A total of 91 adverse events (AEs) were reported, where 98% were grade 1 or 2 and only 2 were grade 3. Three grade 1 AEs in two patients were reported as possibly related to both Radspherin and CRS (night sweats (2), fatigue (1)). Five serious AEs (SAEs) were reported (compression fracture, ileus, paralytic ileus, small intestinal obstruction, intestinal obstruction), according to the investigator not related to Radspherin, but three were related to surgery. One grade 2 event of procedural complication (leakage during administration) was reported as SAE because being medically important. No complications have been identified during follow-up of the patient.
Conclusion All dose levels were well tolerated, DLT was not reached and the highest dose of 7MBq was selected for the expansion cohort. No deaths occurred and only one SAE related to Radspherin administration was reported.
Disclosures Y. Wang has no conflict of interest to report.
E. Van Nieuwenhuysen reports Grants/research support from Amgen, Eli Lilly and consulting fees from Regeneron, Oncoinvent and AstraZeneca.
T. Skeie-Jensen has no conflicts to report.
T. Van Gorp reports grants/research support from Amgen, Roche and AstraZeneca; consulting fees from AstraZeneca, Eisai, GSK, Immunogen, MSD/Merck, OncXerna Therapeutics, Seagen and Tubulis; travel expenses from GSK, Pharmamar, MSD and Immunogen.
AK. Aksnes reports other support as employee from Oncoinvent.
K. Myren reports other support as employee from Oncoinvent.
I. Vergote reports grants/reseach support from Oncoinvent, Amgen and Roche; consulting fees from Agenus, Akesobio, AstraZeneca, Bristol Myers Squibb, Deciphera Pharmaceuticals, Eisai, Elevar Therapeutics, F Hoffmann-La Roche, Genmab, GSK, Immunogen, Jazzpharma, Karyopharm, Mersana, MSD, Novocure, Novartis, Oncoinvent, OncXerna, Sanofi, Regeneron, Seagen, Sotio, Verastem Oncology, Zentalis; travel expenses from Karyopharm, Genmab and Novocure.
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