Table 3.

Safety and efficacy of selected late line T-cell–directed therapies not targeting BCMA*

NameTargetConstructTrial (NCT#, status)Designn% ORR (sCR, CR); median DOR in months (95% CI); median PFS in months (95% CI) at reported median follow-upSelect safety event % (G3+4%, if any)
AllBCMA-exposedAllBCMA-exposed
MCARH10922  GPRC5D Autologous CART (NCT04555551, active, not recruiting) Phase 1, open-label, single-center (MSKCC), dose escalation 17 10 71% (35% ≥ CR); 7.8 (5.7-NE); NR at 10.1 months
 		70% (40% ≥ CR); NR; NR at 10.1 months CRS 88% (6%), ICANS 6% (6%), nail changes 65%, rash 18%, infections 18% (12%), cerebellar toxicity (12%) 
BMS-986393 (CC 95266)25  GPRC5D Autologous CART (NCT04674813, recruiting) Phase 1, open-label, multienter, dose escalation 21
 		7 86%; NE; NE at 4 months 66.7%; NE; NE at 4 months CRS 65%, ICANS 12%, neutropenia 41% (NR), thrombocytopenia 35% (NR), AEs of skin 18%, nails 12%, dysgeusia/dysphagia 12% 
OriCAR-01723  GPRC5D Autologous CART (bi-epitope nanobody based) POLARIS
(NCT05016778, active, not recruiting) 		Phase 1, open-label, single-center (First Affiliated Hospital of Zhejiang University) 10 5 100% (60% ≥ CR); NE; NE at 7.8 months 100% (40% ≥ CR); NE; NE at 7.8 months CRS 100%, ICANS 0%, anemia 80% (70%), neutropenia 100% (100%), nail disorders 30% 
Anti-GPRC5D CAR T24  GPRC5D Autologous CART (Chinese Clinical Trial Register: ChiCTR2100048888) Phase 2, open-label, single-center (Hospital of Xuzhou Medical University) 33 9 91% (63% ≥ CR); NE; NE at 5.2 months 100% (40% ≥ CR); NE; NE at 5.2 months CRS 76%, ICANS 6% (3%), anemia 100% (52%), neutropenia 100% (100%), thrombocytopenia 100% (45%), nail changes 27%
 
Talquetamab20 † GPRC5D BsAb (humanized IgG4 Fc) MonumenTal-1 (NCT03399799, recruiting; NCT04634552) Phase 1/2, multienter, open-label, dose escalation and dose expansion 143 (0.4 mg/kg SC weekly), 145 (0.8 mg/kg SC q2 wk) 51 (36 CART, 18 BsAb) 0.4  mg/kg: 74.1% (33.6% ≥ CR) 9.5 (6.7-13.3); 35% at 12 months
0.8  mg/kg: 71.7% (38.7% ≥ CR); NE (13.0-NE); 54% at 12 months 		64.7% (35.3 ≥ CR %); 11.9 (4.8-NE); 38% at 12 months
(ORR 75% in patients with prior CART and 44% with prior BsAb) 		0.4 mg/kg: CRS 79% (2.1%), dysgeusia 63%, anemia 44.8% (31.5%), skin-related AEs 63%, nail disorders 51.7%, infections 57.3% (16.8%)
0.8 mg/kg: CRS 80% (0.7%), dysgeusia 46.2%, anemia 39.3% (24.8%), skin-related AEs 67.6% (0.7%), nail disorders 43.4%, infections 50.3% (11.7%)
 
Forimtamig (RG6234)21† GPRC5D BsAb (2:1 humanized antibody) (NCT04557150, recruiting) Phase 1, multienter, dose escalation and dose expansion 51 (IV), 57 (SC) 11 (IV), 12 (SC) (21 evaluable) IV: 71.4% (34.7% ≥ CR); 10.8 (0-17.6); NR at 11.6 months
SC: 63.6% (25.5% ≥ CR); 12.5 (1.2-12.5); NR at 8 months 		IV: 50%; NR; NR
SC: 54.5%; NR; NR
 		IV: CRS IV 82.4% (2.0%), ICANS 9.8% (2.0%), skin toxicity 78.4% (11.8%), hair and nail toxicity 23.5%, infections 56.9% (19.6%)
SC: CRS 78.9% (1.8%), ICANS 12.3% (3.6%), skin 86% (22.8%), hair and nail toxicity 28.1%, infections 37.0% (24.1%) 
Cevostamab26† FCRH5 BsAb (Humanized IgG1 Fc) GO39775 (NCT03275103, recruiting) Phase 1, multienter, fixed-duration of 17 cycles; 90 and 160 mg dose expansion cohorts 161 (86 90 mg and 44 160 mg target dose level evaluable patients)† 54 (27 CART, 13 BsAb, 27 ADC)—some patients had multiple BCMA therapies 90 mg: 36.1% (9.6% ≥ CR); 11.5 (6.0-18.4; NR at 14.3 months
160 mg: 56.7% (8.4% ≥ CR); NR; NR at 6.5 months 		All: 36.4%
CART: 44.4%
BsAbs: 33.3%
ADCs: 50.0%
 		CRS 80.7% (1.2%), ICANS 14.3% (0.6%), infections 42.5% (18.8%), neurological/psychiatric 40.6% (3.8%), anemia 31.9% (21.9%) 
NameTargetConstructTrial (NCT#, status)Designn% ORR (sCR, CR); median DOR in months (95% CI); median PFS in months (95% CI) at reported median follow-upSelect safety event % (G3+4%, if any)
AllBCMA-exposedAllBCMA-exposed
MCARH10922  GPRC5D Autologous CART (NCT04555551, active, not recruiting) Phase 1, open-label, single-center (MSKCC), dose escalation 17 10 71% (35% ≥ CR); 7.8 (5.7-NE); NR at 10.1 months
 		70% (40% ≥ CR); NR; NR at 10.1 months CRS 88% (6%), ICANS 6% (6%), nail changes 65%, rash 18%, infections 18% (12%), cerebellar toxicity (12%) 
BMS-986393 (CC 95266)25  GPRC5D Autologous CART (NCT04674813, recruiting) Phase 1, open-label, multienter, dose escalation 21
 		7 86%; NE; NE at 4 months 66.7%; NE; NE at 4 months CRS 65%, ICANS 12%, neutropenia 41% (NR), thrombocytopenia 35% (NR), AEs of skin 18%, nails 12%, dysgeusia/dysphagia 12% 
OriCAR-01723  GPRC5D Autologous CART (bi-epitope nanobody based) POLARIS
(NCT05016778, active, not recruiting) 		Phase 1, open-label, single-center (First Affiliated Hospital of Zhejiang University) 10 5 100% (60% ≥ CR); NE; NE at 7.8 months 100% (40% ≥ CR); NE; NE at 7.8 months CRS 100%, ICANS 0%, anemia 80% (70%), neutropenia 100% (100%), nail disorders 30% 
Anti-GPRC5D CAR T24  GPRC5D Autologous CART (Chinese Clinical Trial Register: ChiCTR2100048888) Phase 2, open-label, single-center (Hospital of Xuzhou Medical University) 33 9 91% (63% ≥ CR); NE; NE at 5.2 months 100% (40% ≥ CR); NE; NE at 5.2 months CRS 76%, ICANS 6% (3%), anemia 100% (52%), neutropenia 100% (100%), thrombocytopenia 100% (45%), nail changes 27%
 
Talquetamab20 † GPRC5D BsAb (humanized IgG4 Fc) MonumenTal-1 (NCT03399799, recruiting; NCT04634552) Phase 1/2, multienter, open-label, dose escalation and dose expansion 143 (0.4 mg/kg SC weekly), 145 (0.8 mg/kg SC q2 wk) 51 (36 CART, 18 BsAb) 0.4  mg/kg: 74.1% (33.6% ≥ CR) 9.5 (6.7-13.3); 35% at 12 months
0.8  mg/kg: 71.7% (38.7% ≥ CR); NE (13.0-NE); 54% at 12 months 		64.7% (35.3 ≥ CR %); 11.9 (4.8-NE); 38% at 12 months
(ORR 75% in patients with prior CART and 44% with prior BsAb) 		0.4 mg/kg: CRS 79% (2.1%), dysgeusia 63%, anemia 44.8% (31.5%), skin-related AEs 63%, nail disorders 51.7%, infections 57.3% (16.8%)
0.8 mg/kg: CRS 80% (0.7%), dysgeusia 46.2%, anemia 39.3% (24.8%), skin-related AEs 67.6% (0.7%), nail disorders 43.4%, infections 50.3% (11.7%)
 
Forimtamig (RG6234)21† GPRC5D BsAb (2:1 humanized antibody) (NCT04557150, recruiting) Phase 1, multienter, dose escalation and dose expansion 51 (IV), 57 (SC) 11 (IV), 12 (SC) (21 evaluable) IV: 71.4% (34.7% ≥ CR); 10.8 (0-17.6); NR at 11.6 months
SC: 63.6% (25.5% ≥ CR); 12.5 (1.2-12.5); NR at 8 months 		IV: 50%; NR; NR
SC: 54.5%; NR; NR
 		IV: CRS IV 82.4% (2.0%), ICANS 9.8% (2.0%), skin toxicity 78.4% (11.8%), hair and nail toxicity 23.5%, infections 56.9% (19.6%)
SC: CRS 78.9% (1.8%), ICANS 12.3% (3.6%), skin 86% (22.8%), hair and nail toxicity 28.1%, infections 37.0% (24.1%) 
Cevostamab26† FCRH5 BsAb (Humanized IgG1 Fc) GO39775 (NCT03275103, recruiting) Phase 1, multienter, fixed-duration of 17 cycles; 90 and 160 mg dose expansion cohorts 161 (86 90 mg and 44 160 mg target dose level evaluable patients)† 54 (27 CART, 13 BsAb, 27 ADC)—some patients had multiple BCMA therapies 90 mg: 36.1% (9.6% ≥ CR); 11.5 (6.0-18.4; NR at 14.3 months
160 mg: 56.7% (8.4% ≥ CR); NR; NR at 6.5 months 		All: 36.4%
CART: 44.4%
BsAbs: 33.3%
ADCs: 50.0%
 		CRS 80.7% (1.2%), ICANS 14.3% (0.6%), infections 42.5% (18.8%), neurological/psychiatric 40.6% (3.8%), anemia 31.9% (21.9%) 

AE, adverse event; RP2D, recommended phase 2 dose.

*

Nonexhaustive list of select ongoing trials (search May 18, 2023)—for a comprehensive list, please visit clinicaltrials.gov.

†

Updated data presented during ASH 2021, ASH 2022, or ASCO 2023 meetings.

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