112: Pharmacokinetics & Safety of Teclistamab Administered in the Arm or Thigh of Patients With Relapsed/Refractory Multiple Myeloma in MajesTEC-1

Statement of Purpose, Innovation or Hypothesis: Teclistamab (tec) is the first B-cell maturation antigen×CD3 bispecific antibody (IgG-4 PAA) approved for the treatment of patients (pts) with triple-class exposed relapsed/refractory multiple myeloma (RRMM). In the population that received the recommended phase 2 dose (RP2D) in MajesTEC-1, the abdomen was the preferred injection site. Factors such as regional differences in the composition of the hypodermis, blood and lymph flow, pre-systemic catabolism, and neonatal Fc receptor binding can influence absorption and relative bioavailability of drugs. Based on published data on the assessment of injection site–based pharmacokinetics (PK) of therapeutic biologics, immunoglobulins are less likely to show site-dependent PK compared with peptides/small proteins and non-immunoglobulin proteins (Zou et al, J Control Release, 2021). Hence, we hypothesized that there would be no differences in tec exposure when administered in anatomic sites other than the abdomen. To assess the impact of injection site on tec disposition, tec subcutaneous administration in the abdomen, arm, and thigh was evaluated in the phase 1/2 MajesTEC-1 study (NCT03145181/NCT04557098).

Description of Methods & Materials: Administration of tec in the arm or thigh was evaluated in specific cohorts in MajesTEC-1. Tec was administered subcutaneously at the RP2D dose (1.5 mg/kg weekly, preceded by 2 step-up doses (ie, 0.06 and 0.3 mg/kg). Serum samples were collected to evaluate tec serum concentrations, and PK parameters were determined for cycles 1 and 3 using non-compartmental analysis (NCA). Cytokine release syndrome (CRS) was graded per Lee et al, Blood, 2014 criteria, and local injection site reactions (ISRs) were graded per CTCAE v.4.03. Rates of CRS and ISRs were evaluated through cycle 3 day 7 to remain consistent with the period in which arm/thigh administration occurred.

Data & Results: Tec administration in the arm or thigh was evaluated in 12 pts (6 per cohort). Serum concentrations following tec administration in the arm or thigh during cycles 1–3 and NCA PK parameters were comparable with those observed in pts who received tec in the abdomen at the RP2D in phase 1 (n=40). Incidence of CRS was 66.7% (4/6) and 83.3% (5/6) when tec was administered in the arm or thigh, respectively. Most CRS events were grade 1 (no grade ≥3 events were observed) and had a median duration of 2 days. ISRs were observed in 50% (3/6; all grade 1) and 0% of pts receiving tec in the arm or thigh, respectively.

Interpretation, Conclusion or Significance: Despite the small number of pts in this cohort, clinical experience with tec administration in the arm or thigh showed that exposure was comparable with that observed in pts receiving tec in the abdomen. CRS events were low grade, manageable, and in general comparable with the phase 1 RP2D population in MajesTEC-1. No ISRs occurred in the thigh administration cohort. The arm administration cohort had a comparable rate of ISRs vs the phase 1 RP2D population. Overall, current clinical data suggest that the arm and thigh are viable alternative injection sites for tec in pts with RRMM.

Disclosures: NQC, LK, KC, TS, CH, AZ, KQ, and YG are employees of Janssen. NT is a contracted employee of Johnson & Johnson.

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Additional Information/Authors: Acknowledgements: This study was funded by Janssen Research & Development, LLC. Medical writing support was provided by Ashley Thoma, PharmD, of Eloquent Scientific Solutions, and funded by Janssen Global Services, LLC.