Second Generation MUC1-CAR T Therapy Cleared for Solid Tumor Trial

The FDA has accepted Minerva Biotechnologies’ investigational new drug application for a MUC1*-targeting chimeric antigen receptor (CAR) T-cell therapy huMNC2-CAR22 for the potential treatment of solid tumors.¹

“These 1XX mutations solve the two hurdles that have thus far stood in the way of an effective CAR T treatment for solid tumor cancers: 1) CAR T cell exhaustion; and 2) failure to kill the low antigen expressing cells,” Cynthia Bamdad, PhD, chief executive and scientific officer, Minerva, said in a statement.¹ “Together with our MUC1* antibodies that recognize an epitope only available on cancer cells, huMNC2-CAR22 promises to be a big leap ahead in our fight against cancers.”

huMNC2-CAR22 will be evaluated in an ongoing phase 1/2 study (NCT04020575) alongside huMNC22-CAR44 that is currently being evaluated for the potential treatment of metastatic breast cancer. Minerva stated that CAR T-cell expansion has been observed in this trial along with best responses of stable disease and partial response with huMNC22-CAR44 treatment. However, the company has developed huMNC2-CAR22 with 1XX mutations in the CD3-z signaling domain to reduce T-cell exhaustion, increase persistence, and therefore produce a more durable response. Minerva also asserted that the 1XX mutations allow CAR cells to recognize and kill the low MUC1*-expressing cancer cells to mimize cancer recurrence.

“The ability of our antibody to bind specifically to the cancerous form of MUC1 without binding to MUC1 on normal tissues is a real breakthrough,” Bambad said in an earlier statement about the opening of the clinical trial.²

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The study, which is being conducted at City of Hope, currently has 4 planned arms of huMNC22-CAR44 treatment, the first a 3+3 dose-escalation and the other 3 evaluating the recommended phase 2 dose (RP2D) in 15 patients each with luminal (hormone receptor positive, HER2 negative), HER2+, and triple negative metastatic breast cancer. The study is primarily evaluating safety as measured by the incidence of adverse events (AEs), the maximum tolerated dose, and RP2D. Secondary end points include in vivo CAR T-cell persistence and antitumor activity.

“Demonstration of safety and early signs of efficacy of huMNC2-CAR44 represent a significant milestone for Minerva. We have a broad, deep pipeline that includes next generation CAR Ts, with enhanced in vivo persistence, and the ability to target cells with much lower antigen density, allowing us to challenge the persistence issues seen elsewhere in the field. We can now progress these to the clinic with increased confidence. We are also developing therapeutics that target the onco-embryonic growth factor, NME7, that activates the MUC1* growth factor receptor across many different types of solid tumors and the preclinical results are very encouraging,” Michael Crowther, chief business officer, Minerva, added to the earlier statement.²

Minerva is evaluating additional second generation MUC1 CAR T therapies that include a huMNC2-CAR with a secreted factor to increase persistence and huMNC2-CAR44 with an inducible localized checkpoint inhibitor. These are currently in preclinical phases of development.

REFERENCES

1. Minerva Biotechnologies gets FDA approval of IND for a MUC1*-CAR-1XX with increased persistence and ability to kill low antigen expressing cells for treatment of solid tumor cancers. News release. Minerva Biotechnologies. https://bizwire.pslgroup.com/20230109005010r1.html
2. Minerva Biotechnologies announces opening 1st-in-human phase I/II trial of a MUC1* targeting CAR T for metastatic breast cancers at City of Hope. News release. Minerva Biotechnologies. February 1, 2022. https://www.minervabio.com/news/minerva-biotechnologies-announces-opening-1st-in-human-phase-i-ii-trial-of-a-muc1-targeting-car-t-for-metastatic-breast-cancers-at-city-of-hope/