After chat with FDA, ImmunoGen delays pivotal top-line data on blood cancer ADC to 2024

ImmunoGen is rethinking the pivotal program for blood cancer antibody-drug conjugate (ADC) pivekimab sunirine.

After talking to the FDA, the biotech is focusing its phase 2 trial on patients without prior or concomitant hematologic malignancy (PCHM), causing the top-line data drop to slip two years, from 2022 to 2024.

Massachusetts-based ImmunoGen originally designed the phase 2 CADENZA trial to enroll patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN), regardless of whether they had PCHM. However, after seeing data from the first 10 patients, six of whom had PCHM, and talking to the FDA, the biotech is focusing its primary efficacy analysis for the CD123-targeting ADC on patients with de novo disease. 

The change will delay the delivery of top-line data. ImmunoGen went into 2022 aiming to report top-line data from CADENZA in the second half of the year. The narrowing of the focus of the trial will require the enrollment of additional de novo patients, pushing the top-line data out to 2024.

ImmunoGen made the change after seeing a divergence between the outcomes of de novo and PCHM patients. While the biotech has seen complete responses in PCHM patients, it now argues the presence of the prior or concomitant malignancy will stop full hematological recovery in most people. As such, ImmunoGen thinks complete response with partial hematological recovery is meaningful in PCHM.

Of the six PCHM patients in CADENZA, four experienced some form of complete response, including with partial hematological recovery. The problem? ImmunoGen chose complete response or clinical complete response (CR/CRc) as the primary endpoint of the study. Two of the four de novo patients had a CR/CRc, but pivekimab looks less able to trigger such responses in PCHM. 

The revised study will use CR/CRc in de novo BPDCN patients as the primary endpoint, with duration of response as a key secondary endpoint. So far, ImmunoGen has enrolled six de novo patients in CADENZA and expects to enroll up to 20 such patients for the efficacy analysis while continuing to explore the use of the therapy in PCHM. The need to enroll extra de novo patients has delayed the readout.

ImmunoGen had $373.9 million in cash and equivalents at the end of the June, but the delay will still put the readout toward the end of its cash runway, which was slated to fund operations into 2024 at the last count. 

The ADC is designed to deliver a DNA-acting IGN payload with high potency against leukemic blasts to cells that express CD123. While ImmunoGen is initially targeting BPDCN, it sees potential to expand use of the wholly owned molecule to acute myeloid leukemia.