FDA Grants Tentative Approval to PNT2003 for GEP-NETs

The FDA granted tentative approval to PNT2003 (lutetium Lu 177 dotatate), a radioequivalent version of lutetium Lu 177 dotatate (Lutathera), for the treatment of adult patients with somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs), according to a news release from the developer, Lantheus Holdings, Inc.¹

The regulatory decision followed the acceptance of an abbreviated new drug application (ANDA) that included a paragraph IV certification.^2,3 This approval sought to provide a therapeutic alternative for patients with cancer of the foregut, midgut, and hindgut. While PNT2003 met all required quality, safety, and efficacy standards for approval, the tentative status indicated that the product was subject to existing patent protections or exclusivity periods associated with the reference drug.

The clinical efficacy supporting the initial approval of reference lutetium Lu 177 dotatate in GEP-NETs was primarily established through the phase 3 NETTER-1 trial (NCT01578239), which compared the radiopharmaceutical plus octreotide (Sandostatin) against octreotide alone.⁴ In this study, the use of lutetium Lu 177 dotatate resulted in a significant improvement in progression-free survival (PFS; HR, 0.21; 95% CI: 0.13-0.32). At the time of the primary analysis, the median PFS for the group receiving lutetium Lu 177 dotatate had not been reached, while the control group—which received high-dose, long-acting octreotide—experienced a median PFS of 8.5 months.

Further evidence came from the ERASMUS Medical Center (MC) trial, a single-arm study involving 1214 patients. In the subset of 360 patients with GEP-NETs, the objective response rate (ORR) per RECIST v1.1 criteria was 16%. Moreover, 3 complete responses were observed in this subset of patients.

“As the first radioequivalent to [lutetium Lu 177 dotatate] to receive FDA tentative approval, PNT2003 marks an important step forward in Lantheus’ work to advance treatment options for patients with GEP-NETs,” Mary Anne Heino, chief executive officer of Lantheus, said in the news release.¹ “This milestone comes at a time when advances in imaging and evolving clinical guidelines are enabling the identification of more patients who stand to benefit from targeted radiopharmaceutical therapies. As the leading radiopharmaceutical-focused company, we remain committed to meeting this growing demand and look forward to making PNT2003 available to patients pending final FDA approval.”

In the NETTER-1 trial, patients in the experimental arm received lutetium Lu 177 dotatate at a dose of 7.4 GBq (200 mCi) every 8 weeks for a total of 4 doses. This was administered in conjunction with long-acting octreotide at 30 mg given every 4 weeks. The control group received long-acting octreotide intramuscularly at a dose of 60 mg every 4 weeks.

The NETTER-1 trial enrolled 229 patients with progressive, somatostatin receptor-positive midgut NETs. All patients included in the study had tumors that were well-differentiated and demonstrated somatostatin receptor expression on imaging.

The second study, the ERASMUS MC trial, was an open-label, single-arm, single-institution study conducted in the Netherlands. This trial assessed 1214 patients with somatostatin receptor-positive tumors who received lutetium Lu 177 dotatate at the same dose of 7.4 GBq (200 mCi) every 6 to 13 weeks for up to 4 doses. Within this larger cohort, 360 patients were identified as having GEP-NETs.

The primary end point for the NETTER-1 trial was PFS, as determined by a blinded independent radiology committee (BICR) using RECIST v1.1 criteria. Secondary end points included ORR and safety. For the ERASMUS MC trial, the primary end points were ORR, PFS, and overall survival.

In the NETTER-1 trial, the most common grade 3 or 4 AEs reported at the time of the approval included lymphopenia (44%), increased GGT (20%), and vomiting (7%). Additionally, myelodysplastic syndrome events were reported in 2.7% of patients in the radiopharmaceutical arm.

References

1. Lantheus receives FDA tentative approval for lutetium Lu 177 dotatate (PNT2003), radioequivalent to LUTATHERA®. News release. Lantheus Holdings, Inc. March 2, 2026. Accessed March 2, 2026. https://tinyurl.com/mryt82jx
2. Lantheus announces acceptance of its first-to-file ANDA for generic LUTATHERA® (Lutetium Lu 177 Dotatate). News release. Lantheus Holdings, Inc. January 11, 2024. Accessed March 2, 2026. https://tinyurl.com/2p9jpcv6
3. Patent certifications and suitability petitions. FDA. Updated February 9, 2026. Accessed March 2, 2026. https://tinyurl.com/5h92d8uk
4. FDA approves lutetium Lu 177 dotatate for treatment of GEP-NETS. News release. FDA. January 26, 2018. Accessed March 2, 2026. https://tinyurl.com/4w3vms7y