The US Food and Drug Administration (FDA) has issued a complete response letter (CRL) to Spectrum Pharmaceuticals regarding the new drug application (NDA) for poziotinib, a tyrosine kinase inhibitor being investigated for patients with previously treated, locally advanced or metastatic non-small cell lung cancer (NSCLC) with HER2 exon 20 insertion mutations.

According to the CRL, the application could not be approved in its present form, as additional data, including a randomized controlled trial, would be required prior to making a decision. The NDA currently includes data from cohort 2 of the open-label, phase 2 ZENITH20 trial ( Identifier: NCT03318939).

Findings from the study, which included 90 participants, showed a confirmed objective response rate of 27.8%. Partial response was observed in 25 patients, and the disease control rate was 70%. Drug interruption occurred in 87% of patients, with 12% (n=11) permanently discontinuing treatment. In September, the FDA’s Oncologic Drugs Advisory Committee (ODAC) voted 9-4 that the current benefits of poziotinib did not outweigh the risks.

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“While we are not surprised by the CRL given the ODAC recommendation in September, we are disappointed. After multiple interactions with the FDA since ODAC, and following careful consideration, we have made the strategic decision to immediately de-prioritize the poziotinib program,” said Tom Riga, president and chief executive officer of Spectrum Pharmaceuticals. “We continue to believe that poziotinib could present a meaningful treatment option for patients with this rare form of lung cancer, for whom other therapies have failed.”

Data presented at ESMO Congress 2022 suggested that poziotinib was active in patients with the G778_P780dup HER2 exon 20 insertion mutation. Of the 14 evaluable patients, 12 had a partial response, resulting in an ORR of 85.7%. The ORR was reported to be 100% in previously treated patients from cohort 2.


Spectrum Pharmaceuticals receives complete response letter from US Food and Drug Administration for poziotinib; reaffirms focus on the commercialization of Rolvedon™ (eflapegrastim-xnst) injection. News release. November 25, 2022. Accessed November 28, 2022.

This article originally appeared on MPR