P=N/A, N=27, Recruiting, Bristol-Myers Squibb | Not yet recruiting --> Recruiting

P2, N=72, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Jun 2024 --> Jun 2025 | Trial primary completion date: Jun 2024 --> Jun 2025

This phase 1 clinical trial demonstrates that early introduction of immunotherapy after ASCT is well tolerated and shows promising disease control in patients with MM, accompanied by favorable changes in the immune microenvironment.

P2, N=67, Active, not recruiting, Bristol-Myers Squibb | Trial completion date: Mar 2024 --> Jun 2024 | Trial primary completion date: Mar 2024 --> Jun 2024

P2, N=52, Active, not recruiting, Massachusetts General Hospital | Trial completion date: Jun 2022 --> Jun 2025 | Trial primary completion date: Jun 2022 --> Dec 2024

P1, N=19, Active, not recruiting, Massachusetts General Hospital | Phase classification: P1b --> P1 | Trial completion date: Jun 2023 --> Sep 2024 | Trial primary completion date: Jun 2023 --> Sep 2024

SLAMF7 is expressed in the interstitial components of clinical OC tissue, and higher SLAMF7 expression indicated a favorable prognosis for patients with OC. Additionally, SLAMF7 is involved in T-cell immune infiltration in OC.

In conclusion, this study highlights SLAMF7 as a regulator of macrophage function and a potential predictive biomarker of immunotherapy response in HCC. Strategies targeting CCL2 signaling to induce macrophage repolarization in HCC with low SLAMF7 might enhance the efficacy of immunotherapy.

Furthermore, the augmentation of the antitumor effects of CD16-independent NK cells upon pretreatment with Elo enhanced the expression of CRTAM, TNFRSF9, EAT-2, and FOXP3 genes and reduced the expression of HSPA6. Our results suggest that Elo directly promotes the cytotoxic function of CD16-independent NK cells against target cells, which is associated with the upregulation of the expression of several NK cell-enhancing genes.

When the cutoff value of CD4/CD8 ratio was 0.792 according to ROC curves, the two-year time to next treatment (TTNT) in the low CD4/CD8 group was significantly longer than that in the high CD4/CD8 group (80.0% vs. 15.0%, p=0.024). The change in NK cells and CD8+ Tregs predicted long-duration ERd and PD, and maintaining low CD4/8 ratio predicted long TTNT, suggesting that these lymphocyte fractions might be biomarkers for a durable therapeutic effect of ERd in myeloma patients.

P2, N=113, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Apr 2024 --> Apr 2025 | Trial primary completion date: Apr 2024 --> Apr 2025

P2, N=53, Recruiting, Medical College of Wisconsin | Trial completion date: Jan 2025 --> Jan 2026 | Trial primary completion date: Jan 2024 --> Jan 2025

Addition of elotuzumab to RVd induction or consolidation and lenalidomide maintenance in patients with transplant-eligible newly diagnosed multiple myeloma did not provide clinical benefit. Elotuzumab-containing therapies might be reserved for patients with relapsed or refractory multiple myeloma.

Further, we provide evidence that, unlike anti-CD38 CAR-T, which elicited a rapid immune reaction against hematopoietic cells in a humanized mouse model, DCAR-T showed no signs of toxicity. Thus, DCAR-T could provide a safe and efficient alternative to anti-BCMA CAR-T to treat MM patients.

P1, N=6, Enrolling by invitation, Icahn School of Medicine at Mount Sinai | Recruiting --> Enrolling by invitation | N=31 --> 6 | Trial completion date: Aug 2025 --> Aug 2027 | Trial primary completion date: Dec 2023 --> Aug 2024

P2, N=40, Active, not recruiting, Dana-Farber Cancer Institute | Trial completion date: Dec 2023 --> Mar 2024

P2, N=8, Terminated, National Institute of Allergy and Infectious Diseases (NIAID) | N=75 --> 8 | Trial completion date: Nov 2026 --> Jan 2024 | Recruiting --> Terminated | Trial primary completion date: Nov 2026 --> Jan 2024; The study was terminated early based on disease flare/lack of efficacy in the early phase of the trial.

P2, N=67, Active, not recruiting, Bristol-Myers Squibb | Trial completion date: Dec 2023 --> Mar 2024 | Trial primary completion date: Dec 2023 --> Mar 2024

P1/2, N=0, Withdrawn, University of Virginia

P1, N=31, Recruiting, Icahn School of Medicine at Mount Sinai

P1/2, N=24, Recruiting, Yale University

P1, N=22, Active, not recruiting, Massachusetts General Hospital

Although the SLAMF7-targeting antibody elotuzumab has no single- agent activity, there is clinical synergy between elotuzumab and immunomodulatory drugs in patients with relapsed/refractory disease. Daratumumab and isatuximab are CD38-targeting antibodies which have single-agent activity and a favorable safety profile, which make these agents an attractive component of combination regimens...All therapeutic antibodies may interfere with assessment of complete response. Next-generation Fc-engineered monoclonal antibodies are in development with the potential to further improve the outcome of patients with MM.

P=N/A, N=27, Not yet recruiting, Bristol-Myers Squibb

P2, N=40, Active, not recruiting, Dana-Farber Cancer Institute | Phase classification: P2a --> P2 | Trial completion date: Jun 2023 --> Dec 2023

Here, we developed a CS1 bsAb (CS1-dbBiTE) using Click chemistry to conjugate intact anti-CS1 antibody (Elotuzumab) and anti-huOKT3 antibody at their respective hinge regions...Similarly, in MM mouse xenograft studies, armed T cells exhibited effective anti-tumor efficacy highlighted by reduced tumor burden in MM.1S tumor-bearing mice compared to controls. On the basis of these findings, the rationale for CS1 targeting by human T cells armed with CS1-dbBiTE presents a potentially effective therapeutic approach for targeting MM.

This study demonstrates that stem cell collection is feasible after prolonged induction with isatuximab-RVd without collection failures and might be further explored as induction therapy.

P1/2, N=0, Withdrawn, University of Virginia | N=18 --> 0 | Recruiting --> Withdrawn

P1, N=20, Active, not recruiting, Massachusetts General Hospital | Phase classification: P1b --> P1 | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Jun 2023 --> Jun 2024

P1, N=22, Active, not recruiting, Massachusetts General Hospital | Phase classification: P1b --> P1

No abstract available

P2, N=41, Active, not recruiting, Mayo Clinic | Trial completion date: Oct 2023 --> Oct 2025 | Trial primary completion date: Oct 2023 --> Oct 2024

Intravenous (IV; 16 mg/kg) or subcutaneous (1800 mg) DARA was given weekly (C1–2), then biweekly (C3–6), and monthly (≥ C7) for subcohorts B1 and B3, and weekly (C1–3) then on D1 of each 21-D (C4–8) or 28-D (≥ C9) cycle for subcohort B2; with weekly oral/IV DEX (40 mg; 20 mg > 75 y or body mass index < 18.5 kg/m2). MeziDd showed promising efficacy and a manageable safety profile in pts with RRMM and 2–4 prior lines of therapy, as did MeziEd in pts with prior anti-CD38 mAb therapy. The immune activity of MEZI was consistent with previous preclinical reports. Improved safety and efficacy may be achieved by schedule and dose adjustments.

Disease was refractory to lenalidomide in all patients, and refractory to both bortezomib and lenalidomide in 3 patients. This is the first ever report combining two different mAbs with dual targeting of CD38 and SLAMF7 in RRMM. The results demonstrate that Isa-EloPD combination is both safe and feasible with high frequency and durability of responses. Despite an anticipated reduction in number, NK cell cytotoxicity remain unaffected with the combination.

There was one grade 3 trAE: specifically, a thromboembolic event in one patient who was receiving lenalidomide and despite aspirin prophylaxis, but who fully recovered. PB and marrow transcriptome profiling along with the immunogenicity studies are in progress and will be presented. We will evaluate whether PB mononuclear cells have the potential to replace BM as a surrogate for genetic and immunological surveillance in SMM, as we anticipate that further understanding of the immune alterations among patients with SMM and the response to immunomodulatory therapy may provide insight on early intervention and prevention of progression to symptomatic disease.

MRD by NGS in the PB was less sensitive compared to the same assessment in the BM by 1-2 logs; however, PB MRD status following 4 cycles of induction therapy was strongly prognostic given its association with PFS. PB MRD status early in treatment may represent a leading indicator of early response and/or a marker of high-risk disease features, and validation of these findings may help to eventually guide intensification of therapy.

The trial investigated elotuzumab in combination with lenalidomide/bortezomib/dexamethasone induction and consolidation, followed by lenalidomide maintenance in transplant-eligible newly diagnosed MM patients and found no progression-free or overall survival advantage with the addition of elotuzumab in any treatment sequence. The efficacy of elotuzumab in MM patients may be influenced by the frequency of regulatory CD8+ T cells after induction therapy. As high levels of regulatory CD8+ T cells showed adverse progression-free survival in MM patients, the assessment of the level of regulatory CD8+ SLAMF7+ T cells could be a prerequisite for MM patients' response to elotuzumab. This study highlights the importance of T cell level-driven immunological treatment approaches when utilizing elotuzumab.

The anti SLAMF7 monoclonal antibody elotuzumab has been used with the immune modulator lenalidomide in relapsed multiple myeloma. SLAMF7 is strongly expressed in HCL. This might suggest SLAMF7 as a target for therapy with elotuzumab. SLAMF7 might also be useful as a potential biomarker for HCL.

Background: Elotuzumab, an anti-SLAMF7 monoclonal antibody, when used in combination with carfilzomib, lenalidomide, and dexamethasone (E-KRd) has shown promising results for treating multiple myeloma (MM). The study found that measuring osteolytic lesion size on sequential whole-body low-dose CT scans by two independent readers is reliable. The sum of lesion sizes can be used as a study endpoint to characterize bone remineralization. Six cycles of E-KRd treatment induce substantial bone remineralization in osteolytic lesions in patients with newly diagnosed MM.

GES scoring was repeated separately for patients receiving anti-PD1 monotherapy (nivolumab; n = 172) or mTOR inhibitor (everolimus; n = 109) monotherapy in the CheckMate-025 cohort. Conclusions We present a GES characteristic of SLAMF7+ CD8+ exhausted T cells that is associated with worse clinical outcomes in patients receiving anti-PD1 monotherapy, but not in patients receiving mTOR inhibitor monotherapy. Future work will aim to validate our findings in additional external RCC cohorts, examine the applicability of our findings to additional cancer types, and experimentally interrogate the impact of SLAMF7 signaling on CD8+ T cell function.

Furthermore, the efficacy of anti-SLAMF7 monoclonal antibodies combined with standard therapies and possible resistance mechanisms will be discussed. This review aimed to provide a detailed summary of the role of SLAMF7 in the pathogenesis of patients with MM and the rationale for further investigation into SLAMF7-mediated molecular pathways associated with MM development.