Elotuzumab is an approved monoclonal antibody targeting SLAMF7 on plasma and NK cells that enhances the activity of lenalidomide, pomalidomide, and bortezomib in multiple myeloma (MM)...Prior therapies included: pomalidomide (33%), daratumumab (25%), and isatuximab (4%)...Common grade ≥3 adverse events were neutropenia (33%); infections, any (33%); lung infection (27%); hypophosphatemia (19%); and thrombocytopenia (15%). Elo-PVd is one of the first trials of a quadruplet regimen in relapsed/refractory MM incorporating a monoclonal antibody to show efficacy across diverse prior treatments, including triple class exposed with prior anti-CD38 monoclonal antibody.

P1, N=7, Active, not recruiting, Icahn School of Medicine at Mount Sinai | Recruiting --> Active, not recruiting | N=24 --> 7 | Trial completion date: Jun 2026 --> Dec 2025 | Trial primary completion date: Jun 2025 --> Nov 2025

P1/2, N=142, Active, not recruiting, SWOG Cancer Research Network | Trial completion date: Sep 2024 --> Mar 2025

P2, N=38, Completed, Mayo Clinic | Active, not recruiting --> Completed

P1/2, N=49, Recruiting, Omar Nadeem, MD | Not yet recruiting --> Recruiting

Human Th1-like Vγ9Vδ2 (γδ) T cells, important effectors against tumors, can be expanded and activated ex vivo by the aminobisphosphonate zoledronic acid in combination with IL-2. These results demonstrate that SLAMF7 is highly expressed in both MM cells and OCs, and that the ex vivo-expanded γδ T cells can exert ELO-mediated ADCC against SLAMF7-expressing MM cells and OCs besides their direct cytotoxic activity. Further study is warranted for the innovative utilization of γδ T cells.

P3, N=222, Recruiting, Stichting European Myeloma Network | Active, not recruiting --> Recruiting | N=109 --> 222

Our results suggest that elotuzumab-containing regimens represent valuable therapeutic options for PI/IMiD-exposed patients with RRMM. In contrast, elotuzumab's role in frontline settings remains limited.

P1, N=24, Recruiting, Icahn School of Medicine at Mount Sinai | Enrolling by invitation --> Recruiting | Trial completion date: Aug 2027 --> Jun 2026 | Trial primary completion date: Aug 2024 --> Jun 2025

P3, N=109, Active, not recruiting, Stichting European Myeloma Network | Recruiting --> Active, not recruiting | N=222 --> 109

Hence, providing SLAMF7 signals during antigen recognition of CD8+ T cells enhanced their overall magnitude, particularly in responses towards low-affinity antigens, resulting in a significant boost in their proliferation and cytotoxic capacity. Overall, we have identified and characterized a potent initiator of the cytotoxic T lymphocyte response program and revealed advanced mechanisms to improve CD8+ T-cell response decisions against weak viral or tumor-associated antigens, thereby strengthening our defense against such adversaries.

P2, N=40, Completed, Dana-Farber Cancer Institute | Active, not recruiting --> Completed | Trial completion date: Jul 2024 --> Jan 2024

P2, N=38, Active, not recruiting, Mayo Clinic | Trial completion date: Oct 2025 --> Oct 2024 | Trial primary completion date: Oct 2024 --> Feb 2024

P2, N=15, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025

P1, N=22, Active, not recruiting, Massachusetts General Hospital | Trial completion date: Sep 2025 --> Sep 2026 | Trial primary completion date: Jun 2024 --> Jun 2025

P1, N=20, Active, not recruiting, Massachusetts General Hospital | Trial completion date: Dec 2025 --> Jun 2026 | Trial primary completion date: Jun 2024 --> Jul 2025

These results demonstrate that UCARTCS1 has potent anti-MM activity against MM cell lines and primary MM cells, as well as in an MM xenograft model and support the evaluation of UCARTCS1 in patients with advanced MM.

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

P1/2, N=49, Not yet recruiting, Omar Nadeem, MD

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

P2, N=15, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting

P1/2, N=142, Active, not recruiting, SWOG Cancer Research Network | Trial completion date: Jun 2024 --> Sep 2024

Not available.

In their BM niche, MM cells adhere to FBs sustaining immune evasion, drug resistance and the undetectable endurance of tumor cells known as minimal residual disease (MRD). Here, we describe the novel bi-specific designed ankyrin repeat protein (DARPin) α-FAPx4-1BB (MP0310) with FAP-dependent 4-1BB agonistic activity. Therefore, α-FAPx4-1BB enhanced both the adhesion of daratumumab-treated NK cells on FBs as well as their activation by improving release of CD107a and perforin, hence MM cell killing via antibody-mediated cell cytotoxicity (ADCC). Interestingly, α-FAPx4-1BB significantly potentiated daratumumab-mediated ADCC in the presence of FBs, suggesting that it may overcome the BM FBs' immunosuppressive effect. Overall, we speculate that treatment with α-FAPx4-1BB may represent a valuable strategy to improve mAb-induced NK cell activity fostering MRD negativity in MM patients through the eradication of latent MRD cells.

We found that by effectively "decorating" the surface of solid tumors with SLAMF7, these nanovesicles directly induced potent and specific antitumor immunity and remodeled the immunosuppressive TME, sensitizing the tumors to programmed cell death protein 1 (PD-1) blockade. Our findings highlight the potential of SLAMF7-targeted multifunctional bispecific nanovesicles as an anticancer strategy with implications for designing next-generation targeted cancer therapies.

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

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