# A multicenter, phase Ib study of subcutaneous administration of isatuximab in combination with pomalidomide and dexamethasone in patients with relapsed/refractory multiple myeloma

Hang Quach, Gurdeep Parmar, Enrique Ocio, H Miles Prince, Albert Oriol, Helen Crowther, Nobuhiro Tsukada, Pierre Bories, Sumit Madan, Nitya Nathwani, et al.

► To cite this version:

Hang Quach, Gurdeep Parmar, Enrique Ocio, H Miles Prince, Albert Oriol, et al. A multicenter, phase Ib study of subcutaneous administration of isatuximab in combination with pomalidomide and dexamethasone in patients with relapsed/refractory multiple myeloma. Haematologica, 2024, 109 (12), pp.4078-4082. 10.3324/haematol.2023.284730. hal-05093487

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https://nantes-universite.hal.science/hal-05093487v1

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# A multicenter, phase Ib study of subcutaneous administration of isatuximab in combination with pomalidomide and dexamethasone in patients with relapsed/refractory multiple myeloma

The availability of subcutaneous (SC) formulations for several anticancer, therapeutic agents has improved safety and convenience of treatment in patients with solid tumors as well as hematologic malignancies, including multiple myeloma.¹⁻³ Compared with intravenous (IV) administration, SC delivery of oncological agents is often preferred by patients and healthcare providers, as it improves comfort and satisfaction for patients and reduces healthcare resource utilization.²,⁴⁻⁶ To enhance convenience of administration, a SC formulation was developed for the anti-CD38 antibody isatuximab (Isa).⁷ Isa is approved for IV use in relapsed/refractory multiple myeloma (RRMM) patients in combination with pomalidomide-dexamethasone (Isa-Pd) after ≥2 prior therapies and with carfilzomib-dexamethasone after one prior therapy.⁸⁻¹²

In this first-in-human, multicenter, phase Ib study (ClinicalTrials.gov: NCT04045795), we assessed the safety, tolerability, pharmacokinetics, and efficacy of Isa administered SC at a fixed dose using an infusion pump (IP) or an investigational on-body delivery system (OBDS) compared with IV Isa administration, both in combination with Pd, in RRMM patients who had received ≥2 prior treatment lines.

Patients were randomized 2:1 to Isa SC administration by IP (Crono IP, Cane', Rivoli, Italy) at a dose of 1,000 mg (IP1000; fixed dose) or IV 10 mg/kg (cohort 1) followed by SC Isa administration by IP at a dose of 1,400 mg (IP1400; fixed dose) or IV 10 mg/kg (cohort 2), plus Pd (Online Supplementary Figure S1A). In the subsequent expansion cohort, SC Isa was administered via a single-use OBDS (Enable Injections, Inc., Cincinnati, OH, USA) (Online Supplementary Figure S1B), at the recommended phase 2 dose (RP2D) of 1,400 mg, plus Pd. SC Isa (10 mL) was delivered by IP or OBDS at a single injection site on the abdomen, which was rotated at each administration. IV and SC Isa were given weekly for 4 weeks and then biweekly in 28-day cycles, with standard doses of pomalidomide and dexamethasone.⁸ Patients received premedication with montelukast (10 mg; only in cycle 1), dexamethasone, acetaminophen, and diphenhydramine. Subsequent premedication in patients who did not experience infusion reactions after four consecutive IV or SC Isa administrations was at the investigator's discretion. Treatment with Isa-Pd continued until disease progression, an unacceptable adverse event, or other reason for discontinuation. The study was approved by the Institutional Review Board or Independent Ethics Committee at each center

and conducted following the Declaration of Helsinki and International Conference on Harmonization Good Clinical Practice guidelines. All patients provided informed consent. Primary study endpoints were safety (including dose-limiting toxicity, evaluated in cycle 1, and injection site reactions), and pharmacokinetics. Main secondary endpoints were overall response rate (according to International Myeloma Working Group criteria¹³), progression-free survival (analyzed using the Kaplan-Meier method), and CD38 receptor occupancy (measured in bone marrow plasma cells at screening and day 1 of cycle 2 pre-dose).

Fifty-six patients with RRMM were treated with Isa-Pd: 12 with Isa IV, 12 with Isa IP1000, and 10 with Isa IP1400 (in dose-escalation); 22 patients in the expansion cohort received Isa delivered by OBDS at the RP2D (Online Supplementary Figure S1C). Two dose-limiting toxicities were observed during dose-escalation: grade 4 neutropenia (IP1000 group) and grade 3 pneumonia (IP1400 group). Both patients resumed study treatment after supportive therapy and dose modifications (pomalidomide dose reduction for the neutropenia; Isa dose omission and pomalidomide-dexamethasone dose reduction for the pulmonary infection).

The RP2D for SC administration of Isa-Pd in patients enrolled in the expansion cohort was determined based on the safety, pharmacokinetics, CD38 receptor occupancy, and efficacy results observed in the Isa IP1000 and Isa IP1400 cohorts. At final data cut-off (March 17, 2023), three (25%) patients in the IV group, three (25%) in the IP1000 group, three (30%) in the IP1400 group, and seven (32%) OBDS patients remained on treatment (Online Supplementary Figure S1C). The median follow-up was longer in the IV (33.0 months), IP1000 (38.8 months), and IP1400 (33.4 months) groups than in the OBDS (19.4 months) group, because of the sequential accrual. The patients' baseline characteristics are presented in Table 1. More patients in the IP1000 and OBDS cohorts were refractory to lenalidomide and a proteasome inhibitor than in the IV and IP1400 cohorts. The median relative dose intensity for SC Isa at the RP2D was ≥90% (97%, 95%, 91%, and 93% in the IV, IP1000, IP1400, and OBDS cohorts, respectively, due to dose delays or dose omissions).

The incidence of all-causality grade ≥3 treatment-emergent adverse events was comparable across cohorts (Table 2). Serious treatment-related adverse events occurred in 16.7%, 25.0%, 50.0%, and 13.6% of patients in the IV, IP1000, IP1400, and OBDS cohorts, respectively. No patient prematurely dis-
LETTER TO THE EDITOR

continued Isa due to a treatment-emergent adverse event. Any-grade, non-hematologic treatment-emergent adverse events reported in ≥25% of patients are listed in *Online Supplementary Table S1*. A grade ≥3 infection occurred in 25%, 25%, 30%, and 36.4% of the IV, IP1000, IP1400, and OBDS patients, respectively, including zero, one (8%), zero, and three (13.6%) patients with grade ≥3 COVID-19 in the corresponding cohorts, due to the concomitance of this trial with the pandemic. Upper respiratory tract infections (all grade 1-2) occurred in 15.6% of patients in the SC cohorts at the RP2D and in 25.0% of patients in the IV cohort with one (8.3%) grade 3 event. Grade 3-4 neutropenia (laboratory abnormality) was observed in 83.3%, 91.7%, 90.0%, and 90.9% of IV, IP1000, IP1400, and OBDS patients, respectively. However, only one (8.3%) patient in the IV cohort, two (20%) in the IP1400 cohort, and two (9.1%) in the OBDS cohort developed febrile neutropenia. Infusion reactions were in-

frequent. A single grade 2 infusion reaction was reported in the IV, IP1000, and IP1400 cohorts (≤10% of patients), at first Isa administration. Importantly, no infusion/injection reactions were observed in OBDS patients.

The median duration of injections at the RP2D was 12.6 min (range, 2.7-31.0) in IP patients and 10.0 min (range, 6.6-49.5) in OBDS patients. All OBDS injections were completed successfully with no interruptions. The local tolerability of SC Isa administration via OBDS was very good: seven (32%) patients experienced injection site reactions (according to customized MedDRA grouping), all grade 1, in 581 administrations (1.7%; 6 events of erythema, 1 hemorrhage, 1 induration, 1 plaque, 1 puncture site bruise).

Slightly lower exposure (C<sub>max</sub>, AUC<sub>last</sub>) was observed during the 1-week dosing period after SC administration than after IV administration, in agreement with slower SC absorption of monoclonal antibodies such as Isa (*Online Supplementary*

<table><caption>**Table 1.** Patients' demographics and baseline characteristics.<sup>a</sup></caption><thead><tr><th>Characteristics</th><th>Isa IV 10 mg/kg + Pd N=12</th><th>Isa IP1000 + Pd N=12</th><th>Isa IP1400 (RP2D) + Pd N=10</th><th>Isa OBDS (RP2D) + Pd N=22</th></tr></thead><tbody><tr><td>Age in years, median (range)</td><td>69.5 (46-83)</td><td>67.0 (50-78)</td><td>72.5 (63-83)</td><td>64.5 (43-82)</td></tr><tr><td>Weight, kg, median (range)</td><td>73.5 (61.3-123)</td><td>70.3 (50.4-93.9)</td><td>86.9 (54.1-96.3)</td><td>71.4 (47.3-104)</td></tr><tr><td>ISS stage at study entry, N (%)</td><td></td><td></td><td></td><td></td></tr><tr><td>I</td><td>4 (33.3)</td><td>8 (66.7)</td><td>4 (40.0)</td><td>11 (50.0)</td></tr><tr><td>II</td><td>6 (50.0)</td><td>4 (33.3)</td><td>6 (60.0)</td><td>9 (40.9)</td></tr><tr><td>III</td><td>2 (16.7)</td><td>0</td><td>0</td><td>2 (9.1)</td></tr><tr><td>Bone marrow plasma cells at baseline, %, median (range)</td><td>7.5 (1-37)</td><td>9.0 (0-95)</td><td>18.5 (0-43)</td><td>10.5 (0-55)</td></tr><tr><td>Beta-2 microglobulin, mg/L, median</td><td>2.9</td><td>2.7</td><td>3.6</td><td>3.0</td></tr><tr><td>Plasmacytoma, N (%)</td><td>2 (16.7)</td><td>3 (25.0)</td><td>1 (10.0)</td><td>4 (18.2)</td></tr><tr><td>Bone lesions present, N (%)</td><td>8 (66.7)</td><td>10 (83.3)</td><td>9 (90.0)</td><td>19 (86.4)</td></tr><tr><td>eGFR (MDRD equation), N (%)</td><td></td><td></td><td></td><td></td></tr><tr><td>≥90 mL/min/1.73 m²</td><td>4 (33.3)</td><td>4 (33.3)</td><td>1 (10.0)</td><td>2 (9.1)</td></tr><tr><td>60≤ eGFR <90 mL/min/1.73 m²</td><td>5 (41.7)</td><td>6 (50.0)</td><td>5 (50.0)</td><td>14 (63.6)</td></tr><tr><td>30≤ eGFR <60 mL/min/1.73 m²</td><td>3 (25.0)</td><td>2 (16.7)</td><td>4 (40.0)</td><td>6 (27.3)</td></tr><tr><td>Number of prior lines of therapy</td><td></td><td></td><td></td><td></td></tr><tr><td>Median (range)</td><td>3.5 (2-7)</td><td>3.0 (2-6)</td><td>2.5 (1-4)</td><td>3.0 (2-6)</td></tr><tr><td>1, N (%) of patients</td><td>0</td><td>0</td><td>1 (10.0)</td><td>0</td></tr><tr><td>2, N (%) of patients</td><td>3 (25.0)</td><td>4 (33.3)</td><td>4 (40.0)</td><td>4 (18.2)</td></tr><tr><td>≥3, N (%) of patients</td><td>9 (75.0)</td><td>8 (66.7)</td><td>5 (50.0)</td><td>18 (81.8)</td></tr><tr><td>Refractory to, N (%)</td><td></td><td></td><td></td><td></td></tr><tr><td>Lenalidomide</td><td>7 (58.3)</td><td>11 (91.7)</td><td>7 (70.0)</td><td>21 (95.5)</td></tr><tr><td>PI</td><td>7 (58.3)</td><td>9 (75.0)</td><td>5 (50.0)</td><td>16 (72.7)</td></tr><tr><td>IMiD and PI</td><td>6 (50.0)</td><td>8 (66.7)</td><td>4 (40.0)</td><td>16 (72.7)</td></tr><tr><td>Daratumumab</td><td>0</td><td>2 (16.7)</td><td>0</td><td>1 (4.5)</td></tr></tbody></table>

<footnote><sup>a</sup>Adult patients with relapsed/refractory multiple myeloma with measurable disease were enrolled if they had received ≥2 prior therapies, had experienced disease progression, and had adequate hematologic, liver, and renal functions. Among key exclusion criteria, patients were not enrolled if they had not achieved a minimal response or better to ≥1 previous treatment lines, were refractory/intolerant to anti-CD38 therapy, had progressed after initial response to anti-CD38 therapy, could not tolerate thromboprophylaxis, or had an excess risk of bleeding. Isa: isatuximab; IV: intravenous; Pd: pomalidomide-dexamethasone; IP: infusion pump; RP2D: recommended phase 2 dose; OBDS: on-body delivery system; ISS: International Staging System; eGFR: estimated glomerular filtration rate; MDRD: Modification of Diet in Renal Disease equation; PI: proteasome inhibitor; IMiD: immunomodulatory drug.</footnote>
LETTER TO THE EDITOR

Table S2). However, similar or higher trough concentrations (C<sub>trough</sub>) at the end of the weekly dosing period – the best pharmacokinetic predictor of efficacy after IV Isa administration¹⁴ – were reached with SC Isa 1,400 mg (IP or OBDS) compared with IV Isa 10 mg/kg. Consistently, the mean C<sub>trough</sub> after multiple dosing was higher in the OBDS than the IV cohort (363 µg/mL and 202 µg/mL, respectively, at day 1 of cycle 3) (*Online Supplementary Table S2*).

High CD38 receptor occupancy saturation was reached by Isa on bone marrow plasma cells in all cohorts. Mean CD38 receptor occupancy (day 1 of cycle 2) was 76.0%, 79.8%, 80.5%, and 77.7% in the IV, IP1000, IP1400, and OBDS patients, respectively. Median decreases in the percentage of cells expressing CD38 versus baseline (49.4% for bone marrow plasma cells; 75.3% for bone marrow natural killer cells) and in CD38 receptor density versus baseline (85.2% on bone marrow plasma cells and 72.6% on bone marrow natural killer cells) were observed after treatment with Isa (day 1 of cycle 2).

Best overall responses are presented in Table 3. The overall response rate was 66.7% in the IV cohort, 66.7% and 80.0% in the IP1000 and IP1400 groups, respectively, and 72.7% for OBDS patients, with a median progression-free survival of 22.0 months, 17.4 months, not reached, and 20.6 months, respectively.

Our results show that the safety and efficacy of Isa administered SC at the RP2D of 1,400 mg, plus Pd, were consistent

with those with IV administration in this study and in the ICARIA-MM trial, with no new safety signals identified.⁸ Infusion reactions were infrequent (≤10%), occurring only at the first injection of Isa in the IV and IP cohorts. This incidence rate of infusion reactions was lower than that observed in the IV Isa trials with the same triplet combination (e.g., 38% in ICARIA-MM).⁸ Notably, premedication was modified in our study by adding montelukast in the first cycle. No infusion reactions were reported in patients who received SC Isa via OBDS, thus demonstrating the safety of this delivery route in the context of combination treatment with an immunomodulatory drug and low-dose dexamethasone. Furthermore, Isa SC administration via OBDS was very well tolerated locally, with only 1.7% of 581 administrations being associated with injection site reactions (all grade 1). Isa was administered IV by weight-based dosing and SC as a flat dose. A low-to-moderate variability was observed for all Isa pharmacokinetic parameters regardless of administration route (IV or SC), dose, or SC delivery modality (by IP or OBDS), supporting the feasibility of switching to a flat dose for SC Isa administration. Although evaluated in a few subjects, analysis of patient-reported outcomes showed a high level of confidence and satisfaction after treatment with SC Isa via OBDS (*data not shown*), indicating acceptance of this delivery approach in clinical practice. Further randomized, confirmatory trials in larger numbers of patients, such as the phase III study IRAKLIA (ClinicalTrials.gov NCT05405166),

<table><caption>**Table 2.** Safety summary.ª</caption><thead><tr><th>Adverse events, N (%)</th><th>Isa IV 10 mg/kg + Pd N=12</th><th>Isa IP1000 + Pd N=12</th><th>Isa IP1400 (RP2D) + Pd N=10</th><th>Isa OBDS (RP2D) + Pd N=22</th><th>Isa OBDS and IP1400 (RP2D) + Pd N=32</th></tr></thead><tbody><tr><td>Any TEAE<sup>b</sup></td><td>12 (100)</td><td>12 (100)</td><td>10 (100)</td><td>22 (100)</td><td>32 (100)</td></tr><tr><td>Grade 3 or 4 TEAE</td><td>12 (100)</td><td>11 (91.7)</td><td>9 (90.0)</td><td>22 (100)</td><td>31 (96.9)</td></tr><tr><td>Treatment-related grade 3 or 4 TEAE</td><td>10 (83.3)</td><td>11 (91.7)</td><td>8 (80.0)</td><td>18 (81.8)</td><td>26 (81.3)</td></tr><tr><td>Grade 5 TEAE</td><td>0</td><td>0</td><td>0</td><td>2 (9.1)<sup>c</sup></td><td>2 (6.3)</td></tr><tr><td>Any serious TEAE</td><td>9 (75.0)</td><td>9 (75.0)</td><td>7 (70.0)</td><td>13 (59.1)</td><td>20 (62.5)</td></tr><tr><td>Any serious treatment-related TEAE</td><td>2 (16.7)</td><td>3 (25.0)</td><td>5 (50.0)</td><td>3 (13.6)</td><td>8 (25.0)</td></tr><tr><td>TEAE leading to definitive treatment discontinuation</td><td>0</td><td>0</td><td>0</td><td>2 (9.1)</td><td>2 (6.3)</td></tr><tr><td>TEAE leading to premature treatment discontinuation</td><td>0</td><td>2 (16.7)</td><td>4 (40.0)</td><td>2 (9.1)</td><td>6 (18.8)</td></tr><tr><td>Isatuximab</td><td>0</td><td>0</td><td>0</td><td>0</td><td>0</td></tr><tr><td>Pomalidomide</td><td>0</td><td>2 (16.7)</td><td>3 (30.0)</td><td>0</td><td>3 (9.4)</td></tr><tr><td>Dexamethasone</td><td>0</td><td>1 (8.3)</td><td>3 (30.0)</td><td>2 (9.1)</td><td>5 (15.6)</td></tr></tbody></table>

<footnote>ªThe safety population comprised all patients who received at least one dose or part of a dose of study drugs. ᵇAdverse events were monitored and graded by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. ᶜTwo patients in the cohort of patients given treatment via an on-body delivery system definitively discontinued treatment due to fatal treatment-emergent adverse events: a cardio-respiratory arrest not related to study treatment and treatment-related Listeria meningitis. Isa: isatuximab; IV: intravenous; Pd: pomalidomide-dexamethasone; IP: infusion pump; RP2D: recommended phase 2 dose; OBDS: on-body delivery system; TEAE: treatment-emergent adverse event.</footnote>
<table><caption>**Table 3.** Best overall response with subcutaneous or intravenous isatuximab in combination with pomalidomide and dexamethasone.ª</caption><thead><tr><th>Response</th><th>Isa IV 10 mg/kg<br>+ Pd<br>N=12</th><th>Isa IP1000<br>+ Pd<br>N=12</th><th>Isa IP1400 (RP2D)<br>+ Pd<br>N=10</th><th>Isa OBDS (RP2D)<br>+ Pd<br>N=22</th><th>Isa OBDS and<br>IP1400 (RP2D)<br>+ Pd<br>N=32</th></tr></thead><tbody><tr><td>Overall response rate, b %</td><td>66.7</td><td>66.7</td><td>80.0</td><td>72.7</td><td>75.0</td></tr><tr><td>Complete response or better</td><td>16.7</td><td>25.0</td><td>30.0</td><td>22.7</td><td>25.0</td></tr><tr><td>Very good partial response</td><td>33.3</td><td>16.7</td><td>10.0</td><td>27.3</td><td>21.9</td></tr><tr><td>Partial response</td><td>16.7</td><td>25.0</td><td>40.0</td><td>22.7</td><td>28.1</td></tr><tr><td>Very good partial response or better, c %</td><td>50.0</td><td>41.7</td><td>40.0</td><td>50.0</td><td>46.9</td></tr></tbody></table>

ªThe efficacy population included all treated patients who had a baseline and at least one post-baseline efficacy assessment as well as patients with early disease progression. ᵇOverall response rate was defined as the proportion of patients with stringent complete response, complete response, very good partial response, and partial response, using the International Myeloma Working Group response criteria. ᶜMinimal residual disease negativity rate (at a 10⁻⁵ sensitivity threshold; exploratory endpoint) was centrally assessed by a next-generation sequencing clonoSEQ assay (Adaptive Biotechnologies, Seattle, WA, USA) in bone marrow aspirates from patients with confirmed very good partial response or better. Minimal residual disease negativity was achieved by one (8.3%) IV patient, none in the IP1000 cohort, two (20.0%) in the IP1400 cohort, and two (9.1%) in the OBDS cohort (4 patients with complete response and 1 with very good partial response). Isa: isatuximab; IV: intravenous; Pd: pomalidomide-dexamethasone; IP: infusion pump; RP2D: recommended phase 2 dose; OBDS: on-body delivery system.

are currently assessing efficacy, safety, and patient-reported outcomes with SC Isa administration via OBDS versus IV Isa, plus Pd in RRMM.

In conclusion, our findings show that SC administration of Isa plus Pd is comparable to IV administration and a promising, convenient treatment approach for patients with RRMM.

## Authors

Hang Quach,¹ Gurdeep Parmar,² Enrique M. Ocio,³ H. Miles Prince,⁴ Albert Oriol,⁵ Helen Crowther,⁶ Nobuhiro Tsukada,⁷ Pierre Bories,⁸ Sumit Madan,⁹ Nitya Nathwani,¹⁰ Kazutaka Sunami,¹¹ Dorothee Semiond,¹² Disa Yu,¹² Paul Cordero,¹³ Sandrine Macé,¹⁴ Florence Suzan¹⁴ and Philippe Moreau¹⁵

¹Clinical Hematology Service, St Vincent's Hospital, University of Melbourne, Melbourne, Australia; ²Illawarra Cancer Care Center, Wollongong, Australia; ³Hospital Universitario Marqués de Valdecilla (IDIVAL), Universidad de Cantabria, Santander, Spain; ⁴Molecular Oncology and Cancer Immunology, Epworth HealthCare and University of Melbourne, Melbourne, Australia; ⁵Institut Català d'Oncologia and Institut Josep Carreras, Hospital Germans Trias i Pujol, Barcelona, Spain; ⁶Department of Hematology, Blacktown and Mount Druitt Hospitals, Blacktown, Australia; ⁷Department of Hematology, Japanese Red Cross Medical Center, Tokyo, Japan; ⁸Early Phase Unit, Institut Claudius Regaud, Institut Universitaire du Cancer de Toulouse, Toulouse, France; ⁹Banner MD Anderson Cancer Center, Gilbert, AZ, USA; ¹⁰Department of Hematology, City of Hope National Medical Center, Duarte, CA, USA; ¹¹Department of Hematology, National Hospital Organization Okayama Medical Center, Okayama, Japan; ¹²Research & Development, Sanofi, Cambridge, MA, USA; ¹³Research & Development, Sanofi, Reading, UK; ¹⁴Research & Development, Sanofi, Vitry-sur-Seine, France; ¹⁵Department of Hematology, University Hospital of Nantes, Nantes, France.

Correspondence:
H. QUACH - Hang.Quach@svha.org.au

https://doi.org/10.3324/haematol.2023.284730

Received: April 19, 2024.

Accepted: August 5, 2024.

Early view: August 15, 2024.

Published under a CC BY license

<figure><img src="image_2.png" /></figure>

## Disclosures

HQ has received research funding from Amgen, Bristol Myers Squibb, GlaxoSmithKline, Karyopharm, and Sanofi and has provided consulting/advisory services for Amgen, Antengene, Beigene, Bristol Myers Squibb, GlaxoSmithKline, Janssen Cilag, Karyopharm, Sanofi, and Takeda. GP has played a consulting/advisory role for Janssen. EMO has received honoraria from Amgen, Bristol Myers Squibb/Celgene, GlaxoSmithKline, Janssen, Oncopeptides, Pfizer, Regeneron, Sanofi, and Takeda; has provided consulting/advisory services for AbbVie, Amgen, Bristol Myers Squibb/Celgene, GlaxoSmithKline, Janssen, Menarini/Stemline Therapeutics, Oncopeptides, Pfizer, Sanofi, and Takeda; participated in speakers' bureau for Janssen; and received travel/accommodation expenses from Bristol Myers Squibb, GlaxoSmithKline, Janssen, and Lilly. HMP, HC, PB, and NN have no conflicts of interest to disclose. AO has played consulting/advisory roles for Amgen, Bristol Myers Squibb, GlaxoSmithKline, Janssen Cilag, Pfizer, and Sanofi. NT has provided consulting/advisory services and participated in speakers' bureau for Sanofi. SM has received research funding from Harpoon Therapeutics and Sanofi; played consulting/advisory roles for Karyopharm, Pfizer, Sanofi, and Takeda; and participated in speakers' bureau for Bristol Myers Squibb, GlaxoSmithKline, Janssen, and Karyopharm. KS has received research funding from AbbVie, Alexion Pharma, Astellas-Amgen, Bristol-Myers Squibb, Celgene, Daiichi Sankyo, GlaxoSmithKline, Janssen, MSD,
Novartis, Ono Pharmaceutical, Sanofi, and Takeda; and played consulting/advisory roles for Bristol-Myers Squibb, Celgene, Janssen, Ono Pharmaceutical, Sanofi, and Takeda. DS is employed by Sanofi and holds patents, royalties, other intellectual property, and Sanofi stock and/or stock options. DY, PC, SM, and FS are employed by Sanofi and may hold stock and/or stock options. PM has received honoraria from or provided consulting/advisory services for AbbVie, Amgen, Celgene, Janssen, Oncopeptides, Roche, and Sanofi.

Contributions

PM, DS, PC, SM, and FS contributed to the conception/design of this study. All authors contributed to collecting and/or analyzing data, as well as the development and final approval of the manuscript.

Acknowledgments

The authors thank the participating patients and their caregivers, the study centers, and the study investigators for their contributions to the study. The authors also thank Honghong Dong, MS, of Sanofi Research & Development, Bridgewater NJ, USA, for her contribution

to the statistical analyses for this study, and BioCytex (a Stago Group company) for their contribution to the immunophenotyping analyses. The on-body delivery system was manufactured by Enable Injections, Inc. Medical writing support was provided by S. Mariani, MD, PhD of Envision Pharma Group.

Funding

This study was funded by Sanofi. The medical writing support was also funded by Sanofi.

Data-sharing statement

Qualified researchers may request access to patient-level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient-level data will be anonymized and study documents will be redacted to protect the privacy of our trial participants. Further details on Sanofi's data-sharing criteria, eligible studies, and process for requesting access can be found at: https://www.vivli.org/.

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