MT2025-14: A Phase 1a/1b Study of GTB-5550, a Camelid Nanobody TriSpecific Killer Engager (camB7-H3 TriKE®), in Select Advanced Solid Tumors That Failed Prior Therapy

Summary

This is a first-in-human Phase 1a/1b trial of a B7-H3-targeted natural killer (NK) cell engager, referred to as a TriSpecific Killer Engager (TriKE), for the treatment of select solid tumor cancers. To be considered for the study, a patient must be 18 years or older, have histologically or cytologically confirmed advanced/metastatic cancer that, based on literature reports, expresses B7-H3 at a high frequency, measurable disease by RECIST 1.1 (exception: mCRPC limited to bone metastasis are exempt from this requirement), meets the disease specific criteria for prior failed therapy, and refractory to, intolerant of, or ineligible for therapy options that are known to provide clinical benefit for their diagnosis.

Detailed description

Enrollment is limited to the following tumor types: * castration-resistant prostate cancer (CRPC) * breast cancer (any ER/PR or HER2 status) * pancreatic cancer * non-small cell lung cancer (NSCLC) * squamous cell carcinoma of the head and neck (SCCHN), including molecularlyconfirmed FA patients * epithelial ovarian cancer (OC), including fallopian tube and primary peritoneal cancer * bladder (urothelial) cancer (UC) * Prostate cancer requires failing at least one line of prior therapy in the castrate resistant setting. * SCCHN patients with a molecularly-confirmed diagnosis of FA are permitted to enroll on the trial if they have unresectable locally advanced or metastatic SCCHN which is ineligible for or has failed radiation therapy. All other diagnoses require failing at least two lines of prior therapy given either in the recurrent and/or metastatic setting. The camelid (cam) anti-CD16/WT IL-15/cam anti-B7-H3 Tri-Specific Killer Engager (camB7-H3 TriKE, also referred to as GTB-5550) is a single chain recombinant TriKE comprised of three components joined by flexible linkers to form a molecule: 1) an arm that engages the CD16 activating receptor (cam anti-CD16) on natural killer (NK) cells; 2) a wildtype IL-15 (WT IL-15) linker arm to drive NK cell proliferation, priming, and survival; and 3) an arm that specifically engages B7-H3 (cam anti-B7-H3) to target the tumor cells. The study is performed in two sequential components as follows: 1. Phase 1a: Dose escalation, open-label component testing up to 6 dose levels of GTB-5550 to identify the MTD using an adaptation of the BOIN design starting with 2 patient cohorts. 2. Phase 1b: Dose expansion component to confirm the MTD identified in the Phase 1a trial across 7 distinct metastatic disease cohorts (castration-resistant prostate cancer, ovarian cancer, breast cancer, head and neck cancer, non-small cell lung cancer, pancreatic cancer, and bladder cancer) and further evaluate its tolerability assuming the toxicity rates are similar across the groups. GTB-5550 is administered by subcutaneous (SQ) injection in the abdominal area for 5 consecutive days (i.e. Monday-Friday) for Cycle 1 Days 1-5 and Days 8-12, followed by 2 weeks off treatment. Starting with Cycle 2 Day 1 and beyond, treatment will be 3 times 2025LS049: GTB-5550 TriKE® for Select Advanced Solid Tumors That Failed Prior Therapy March 19, 2026 Page 27 of 86 confidential per week (but not on 3 consecutive days) for 2 weeks followed by 2 weeks off treatment. One treatment cycle equals 4 weeks (28 days). A minimum of 2 cycles is planned unless medically contraindicated or the participant wishes to discontinue earlier. Patient appropriate disease reassessment is done after 2 cycles (56 days) and every 8 weeks (+/- 1 week) thereafter. Treatment may continue until disease progression, unacceptable toxicity, patient refusal, or treatment is no longer in the best interest of the patient. Patients are followed for 12 months from the 1st dose of GTB-5550 to determine PFS and OS. The primary analysis will be intent-to-treat from the point of 1st injection of GTB-5550 both for toxicity and efficacy.

Arms & interventions

• DrugGTB-5550

  GTB-5550 is given as a subcutaneous (SQ) injection in the abdominal area at the patient-assigned dose once a day for 5 consecutive days for 2 weeks in a row (i.e. Day 1-5 and Day 8-12) followed by 2 weeks of no treatment. This 4-week period equals 1 treatment cycle, or 28 days. Starting with Cycle 2 and beyond, this will be repeated with three times per week dosing for weeks 1 and 2 of the cycle (but not on 3 consecutive days) followed by 2 weeks of no treatment.

Outcome measures

Eligibility criteria