Selpercatinib

A phase I/II trial (LIBRETTO-001 [NCT03157128]) evaluated the safety and efficacy of selpercatinib in adolescent and adult patients with any solid tumor type harboring an activating RET alteration. The primary end point was an objective response (complete response or partial response). The trial enrolled 55 patients with RET-altered MTC who were previously treated with vandetanib, cabozantinib, or both; and 88 patients with RET-altered MTC who were not previously treated with vandetanib or cabozantinib. Eighty two percent of previously treated patients received the recommended phase II dose of 160 mg twice daily, and 98% of previously untreated patients received 160 mg twice daily.[13]

A phase I/II trial (LIBRETTO-001 [NCT03157128]) evaluated the safety and efficacy of selpercatinib in adolescent and adult patients with any solid tumor type harboring an activating RET alteration. The primary end point was an objective response (complete response or partial response). The trial enrolled 55 patients with RET-altered MTC who were previously treated with vandetanib, cabozantinib, or both; and 88 patients with RET-altered MTC who were not previously treated with vandetanib or cabozantinib. Eighty two percent of previously treated patients received the recommended phase II dose of 160 mg twice daily, and 98% of previously untreated patients received 160 mg twice daily.[13]

For patients with RET-altered MTC who were previously treated with vandetanib or cabozantinib:

A phase I/II trial (LIBRETTO-001 [NCT03157128]) evaluated the safety and efficacy of selpercatinib in adolescent and adult patients with any solid tumor type harboring an activating RET alteration. The primary end point was an objective response (complete response or partial response). The trial enrolled 55 patients with RET-altered MTC who were previously treated with vandetanib, cabozantinib, or both; and 88 patients with RET-altered MTC who were not previously treated with vandetanib or cabozantinib. Eighty two percent of previously treated patients received the recommended phase II dose of 160 mg twice daily, and 98% of previously untreated patients received 160 mg twice daily.[13] › For patients with RET-altered MTC who were previously treated with vandetanib or cabozantinib:

The objective response rate was 69% (95% CI, 55%−81%); 9% of patients had a complete response, and 60% of patients had a partial response.

A phase I/II trial (LIBRETTO-001 [NCT03157128]) evaluated the safety and efficacy of selpercatinib in adolescent and adult patients with any solid tumor type harboring an activating RET alteration. The primary end point was an objective response (complete response or partial response). The trial enrolled 55 patients with RET-altered MTC who were previously treated with vandetanib, cabozantinib, or both; and 88 patients with RET-altered MTC who were not previously treated with vandetanib or cabozantinib. Eighty two percent of previously treated patients received the recommended phase II dose of 160 mg twice daily, and 98% of previously untreated patients received 160 mg twice daily.[13] › For patients with RET-altered MTC who were previously treated with vandetanib or cabozantinib:

At 1 year, 86% of responses were ongoing (95% CI, 67%−95%), and 100% of patients were progression-free.

A phase I/II trial (LIBRETTO-001 [NCT03157128]) evaluated the safety and efficacy of selpercatinib in adolescent and adult patients with any solid tumor type harboring an activating RET alteration. The primary end point was an objective response (complete response or partial response). The trial enrolled 55 patients with RET-altered MTC who were previously treated with vandetanib, cabozantinib, or both; and 88 patients with RET-altered MTC who were not previously treated with vandetanib or cabozantinib. Eighty two percent of previously treated patients received the recommended phase II dose of 160 mg twice daily, and 98% of previously untreated patients received 160 mg twice daily.[13]

For patients with RET-altered MTC who were not previously treated with vandetanib or cabozantinib:

A phase I/II trial (LIBRETTO-001 [NCT03157128]) evaluated the safety and efficacy of selpercatinib in adolescent and adult patients with any solid tumor type harboring an activating RET alteration. The primary end point was an objective response (complete response or partial response). The trial enrolled 55 patients with RET-altered MTC who were previously treated with vandetanib, cabozantinib, or both; and 88 patients with RET-altered MTC who were not previously treated with vandetanib or cabozantinib. Eighty two percent of previously treated patients received the recommended phase II dose of 160 mg twice daily, and 98% of previously untreated patients received 160 mg twice daily.[13] › For patients with RET-altered MTC who were not previously treated with vandetanib or cabozantinib:

The objective response rate was 73% (95% CI, 62%−82%); 11% of patients had a complete response, and 61% of patients had a partial response.[13][Level of evidence C2]

A phase I/II trial (LIBRETTO-001 [NCT03157128]) evaluated the safety and efficacy of selpercatinib in adolescent and adult patients with any solid tumor type harboring an activating RET alteration. The primary end point was an objective response (complete response or partial response). The trial enrolled 55 patients with RET-altered MTC who were previously treated with vandetanib, cabozantinib, or both; and 88 patients with RET-altered MTC who were not previously treated with vandetanib or cabozantinib. Eighty two percent of previously treated patients received the recommended phase II dose of 160 mg twice daily, and 98% of previously untreated patients received 160 mg twice daily.[13] › For patients with RET-altered MTC who were not previously treated with vandetanib or cabozantinib:

At 1 year, 91% of responses were ongoing (95% CI, 72%−97%), and 92% of patients were progression-free.

A phase I/II trial (LIBRETTO-001 [NCT03157128]) evaluated the safety and efficacy of selpercatinib in adolescent and adult patients with any solid tumor type harboring an activating RET alteration. The primary end point was an objective response (complete response or partial response). The trial enrolled 55 patients with RET-altered MTC who were previously treated with vandetanib, cabozantinib, or both; and 88 patients with RET-altered MTC who were not previously treated with vandetanib or cabozantinib. Eighty two percent of previously treated patients received the recommended phase II dose of 160 mg twice daily, and 98% of previously untreated patients received 160 mg twice daily.[13]

Treatment-related adverse events (any grade) occurred in 94% of patients.

A phase I/II trial (LIBRETTO-001 [NCT03157128]) evaluated the safety and efficacy of selpercatinib in adolescent and adult patients with any solid tumor type harboring an activating RET alteration. The primary end point was an objective response (complete response or partial response). The trial enrolled 55 patients with RET-altered MTC who were previously treated with vandetanib, cabozantinib, or both; and 88 patients with RET-altered MTC who were not previously treated with vandetanib or cabozantinib. Eighty two percent of previously treated patients received the recommended phase II dose of 160 mg twice daily, and 98% of previously untreated patients received 160 mg twice daily.[13] › Treatment-related adverse events (any grade) occurred in 94% of patients.

Grade 3 adverse events were observed in 28% of patients, and grade 4 adverse events were observed in 2% of patients.

A phase I/II trial (LIBRETTO-001 [NCT03157128]) evaluated the safety and efficacy of selpercatinib in adolescent and adult patients with any solid tumor type harboring an activating RET alteration. The primary end point was an objective response (complete response or partial response). The trial enrolled 55 patients with RET-altered MTC who were previously treated with vandetanib, cabozantinib, or both; and 88 patients with RET-altered MTC who were not previously treated with vandetanib or cabozantinib. Eighty two percent of previously treated patients received the recommended phase II dose of 160 mg twice daily, and 98% of previously untreated patients received 160 mg twice daily.[13] › Treatment-related adverse events (any grade) occurred in 94% of patients.

The most frequent adverse events were dry mouth (46%), hypertension (43%), diarrhea (38%), fatigue (38%), increased aspartate aminotransferase level (35%), nausea (35%), and constipation (35%).

A phase I/II trial (LIBRETTO-001 [NCT03157128]) evaluated the safety and efficacy of selpercatinib in adolescent and adult patients with any solid tumor type harboring an activating RET alteration. The primary end point was an objective response (complete response or partial response). The trial enrolled 55 patients with RET-altered MTC who were previously treated with vandetanib, cabozantinib, or both; and 88 patients with RET-altered MTC who were not previously treated with vandetanib or cabozantinib. Eighty two percent of previously treated patients received the recommended phase II dose of 160 mg twice daily, and 98% of previously untreated patients received 160 mg twice daily.[13] › Treatment-related adverse events (any grade) occurred in 94% of patients.

Thirty percent of patients had dose reductions because of treatment-related adverse events, and 2% of patients discontinued the drug because of adverse events.