Table 1.
Summary of clinical trials of BiTE/BiAb therapy.
| Agents (target) | Trial and participant data | Protocol | Efficacy | Safety |
|---|---|---|---|---|
| Teclistamab (JNJ-64007957) BCMA x CD3 |
1. Phase 1/2 (NCT03145181 and NCT04557098). 2. RRMM, n= 165. 3. Median age: 64 years (range: 33-84). 4. Prior lines of Tx: 5 (2-14) 5. EMD: 17%. 6. Prior HSCT: 81.8% 7. Refractory to anti-CD38 MoAb: 89.7%. 8. Triple/Penta refractory: 77.6%/30.3%. |
1. Once-weekly SC teclistamab at a dose of 1.5 mg/kg (step-up doses of 0.06 and 0.3 mg/kg). | 1. ORR: 63% (104/165), including 97 ≥ VGPR, 65≥ CR. 2. Median time to the first/best response: 1.2/3.8 months. 3. MRD- (10-5): 26.7% (44/165). 4. mPFS/mOS: 11.3/18.3 months. |
1. AEs (any/Gr 3 or 4): 100%/94.5%. 2. Neutropenia (70.9%), anemia (52.1%), thrombocytopenia (40%). 3. Infection: 76.4%, including 44.8% of Gr 3/4. 4. Hypogammaglobulinemia: 74.5%. 5. CRS: 72.1% (most Gr 1 or 2). 6. Neurotoxicity: 14.5% (most Gr 1 or 2), including headache (8.5%). |
| Elranatamab (PF-06863135) BCMA x CD3 |
1. Phase 1 (MagnetisMM-1, NCT03269136) 2. RRMM, n=58 3. Median age: 64 years (range: 32-86). 4. Prior lines of Tx: 6 5. Triple refractory: 98% 6. Prior HSCT: 45%. 7. Prior BCMA-targeted Tx: 22%. 8. Black/African American or Asian: 26%. |
Dosing: Part 1: 80, 130, 215, 360, 600, and 1000μg/kg weekly Parts 1.1 and 2A: single 600μg/kg or equivalent fixed dose of 44mg first, followed 1 week later by 1000μg/kg or equivalent fixed dose of 76mg weekly (Q1W) or every 2 weeks (Q2W) thereafter. LEN or POM combination therapy: single priming dose (32mg), followed 1 week later by the 44mg Q1W thereafter plus LEN (25mg) or POM (4mg) on Days 1 to 21 of a 28-day cycle |
14 patients with confirmed responses. 1. ORR Part 1 (215-1000μg/kg): 70% (14/20), including 6 CR/sCR. At RP2D dose: 83% (5/6) Prior BCMA-targeted Tx: 75% (3/4). 2. Median time to response: 22 days. |
TEAEs: 1. CRS: 48 (83%), none higher than Gr 2. 2. Lymphopenia (n=37, 64%; Gr 3/Gr 4:12%/52%), neutropenia (n=37, 64%; Gr 3/Gr 4:31%/29%), anemia (n= 32, 55%; Gr 3/Gr 4: 38%/0%), injection site reaction (53%), and thrombocytopenia (52%). 3. 2 DLT: 1 Gr 4 thrombocytopenia (part 1.1), 1 Gr4 neutropenia (POM). |
| Linvoseltamab (REGN 5458) BCMA x CD3 |
1. Phase 1/2 (NCT03761108). 2. RRMM, n=73. 3. Median age: 64 years (range: 42-81). 4. 20.5% patients≥ 75 years). 5. Prior lines of Tx: 5 (2-17). 6. Penta refractory: 38.4%. 7. Prior auto-HSCT: 64.4%. |
1. Weekly doses of REGN5458, followed by a maintenance phase administered every 2 weeks (doses ranging from 3-800 mg). | 1. ORR: At 200-800 dose levels: 75.0% (18/24) At all dose levels, 86.5% (32/37) of all responders achieved VGPR and 43.2% (n=16) of responders had a CR or SCR. 2. Estimated DOR ≥8 months: 90.2% |
1. AEs: 73 (100%), including 31 Gr 3 (42.5%) and 24 Gr 4 (32.9%). 2. Fatigue (n= 33, 45.2%), CRS (n= 28, 38.4%) 3. CRS: Gr 1 in 25 pts and Gr 2 in 3 pts. 4. No Gr ≥3 neurotoxicity events 5. Nausea: 24 (32.9%) |
| TNB-383B (ABBV-383) BCMA x CD3 |
1. Phase1 (NCT03933735). 2. RRMM, n=124. (ESC, n=73; ESP (60mg), n=51) 3. Median age: 68 years (range: 35-92). 3. Prior lines of Tx: 5 (3-15). 4. Triple/penta-refractory: 82%/35 (≥ 40mg: 81%/41). 5. Prior HSCT: 81% (≥ 40mg ESC+ EXP: 83%). |
1. IV infusion over 1–2 hours every 3 weeks (Q3W). 2. Dose range: 0.025–120 mg 3. RP2D: 60mg |
Evaluable, n=122 1. ORR: ≥ 40mg ESC + EXP (n=79): 68%, 43 ≥VGPR (54%), 13CR, 16sCR. 60mg EXP: 59% (29/49), 19 ≥VGPR (39%), 7CR, 4sCR. 2. PFS All: 10.4 months ≥ 40mg ESC + EXP/60mg EXP: NR/NR |
Evaluable, n=124 1. Three DLTs (Gr 4 thrombocytopenia, 60mg; Gr 3 CRS, 90 mg and 120 mg) 3. TEAEs: CRS (n= 71, 57%), neutropenia (n= 46, 37%), and fatigue (n= 37, 30%). 3. Infection (≥ Gr3): Pneumonia, COVID-19, sepsis (all n=19, 6%) 4. Seven deaths from TEAEs. |
| Alnuctamab (CC-93269) BCMA x CD3 |
1. Phase1 (NCT03486067). 2. RRMM, n=19 (received Tx). 3. Median age: 64 years (range: 51-78). 4. Prior lines of Tx: 6 (3-12). 5. Prior auto-HSCT: 73.7%. 6. Prior allo-HSCT: 10.5%. 7. Prior lenalidomide/bortezomib: 100%/100%. 8. Prior carfilzomib: 84.2%. 9. Prior pomalidomide: 84.2%. 10. Prior daratumumab: 94.7%. |
IV CC-93269 on days 1, 8, 15, and 22 of cycles 1 to 3, on days 1 and 15 of cycles 4 to 6, and on day 1 of cycle 7 (28-day cycle, up to 2 tears) | 1. ORR: <6 mg: No response. ≥ 6mg: 83.3% (10/12) (MRD-: 75%). |
1. Gr 3-4 AE: 15 (78.9%) 2. Common AEs: Neutropenia (52.6%), anemia (42.1%), infections (26.3%), thrombocytopenia (21.1%). 3. CRS: 89.5% (n=17), including 11 Gr 1 and 2 Gr2. 4. One death due to CRS (≥ 6mg cohort). |
| Talquetamab (JNJ-64407564) GPRC5D x CD3 |
1. Phase 1 (MonumenTAL-1, NCT03399799). 2. RRMM, n=74. 405 μg/kg QW (n=30). 800 μg/kg Q2W (n = 44). 3. Prior lines of Tx: 6 (405)/5 (800). 4. Triple exposed: 100% (405)/98% (800). Triple refractory: 77% (405)/75% (800). |
1. 405 μg/kg SC QW or 800 μg/kg SC Q2W | ORR (405/800) 1. 70% (21/30)/64% (28/44) 2. ≥ VGPR:57%/52% |
AEs (405/800) 1. Cytopenia: 67%/36% (Gr 3/4: 53%/23%). 2. Infections: 47%/34% (Gr 3/4: 7%/9%). 3. CRS: 77%/80% (Gr 3: 3%/0%) 4. Skin-related and nail disorder: 83%/75% (skin exfoliation: 37%/39%, all Gr 1 and 2). 5. Dysgeusia: 63%/57%. |
| RG6234 (RO7425781) GPRC5D x CD3 |
1. Phase 1 (NCT04557150). 2. RRMM, n= 41 (IV, 0.006mg to 10mg) 3. Median age:63 4. Prior lines of Tx: 5 (2-15) 5. HR-cytogenetics: 58% (17/29) 6. Triple/Penta refractory: 67%/36% 7. Prior BCMA-direct Tx: 14.6% (6/41) |
1. Weekly step-up doses followed by a q2w regimen at a peak ‘target dose’ for up to 1 year. | Efficacy evaluable, n=34 1.ORR: 68% (50% ≥ VGPR) 2. Median time to first response: 1.3 months. |
1. CRS: 85.4% (Gr1: 56.1%, Gr2: 24.4%, Gr3: 2.4%). 2. CNS toxicity: 7.3% 3. Gr 3/4: Thrombocytopenia (19.5%), anemia (12.2%), neutropenia (9.8%). 4. Infection: 46.3%, one died of an E. coli sepsis (not related to RG6234). 5. Skin-related AEs: 66% (Gr3: 7.3%), dysgeusia/ageusia (36.6%, all Gr1/2), dry mouth (36.6%, all Gr1/2), dysphagia (17.1%, all Gr1/2), and nail changes (12.2%, all Gr1/2). |
| Cevostamab (BFCR4350A) FcRH5 x CD3 |
1. Phase 1 (NCT03275103). 2. RRMM, n=160. 3. Median age: 64 years (range: 33-82). 4. Prior lines of Tx: 6 (2-18). 5. Triple refractory: 85% 6. ≥ 1 prior CAR-T: 17.5% 7. ≥ 1 prior BiAb: 8.1% 8.≥ 1 prior ADC: 16.9% 9.≥ 1 anti-BCMA: 33.8% |
1. Single set-up cohort (SS): set-up dose (0, 05-3.6mg) on cycle (C) 1 day (D) 1, target dose (0.15-198 mg) on C1D8. 2. Double set-up cohort (DS): set-up dose on C1D1 (0.3-1.2mg) and C1D8 (3.6mg), target dose (60-160mg) on C1D15. 3. IV cevostamab was administered on a 21-day cycle, up to a total of 17 cycles. |
1. Responses (+) at the 20-198mg target dose level. 2. Median time to response: 29 days 3.ORR: 160mg level: 54.5% (24/44). 90mg level: 36.7% (22/60). 4. ORR (> 90mg) Prior CAR-T: 44.4% (4/9). Prior BiAb: 33.3 (3/9). Prior ADC: 50% (7/14). Prior anti-BCMA Tx: 36.4% (8/22). |
1. ≥1 TEAE: 99.4%. 2. CRS: 80% (128/160), only 2 Gr 3. 3. Most CRS (83.4%) resolved within 2 days. 4. ICANS: 13.1% 5. Any SAE: 55.6% (Tx related: 25%) 6. Any Gr 5 AE: 15% (Tx related: 0.6%). |
ADC, antibody-drug conjugate; AE, adverse event; CAR-T, chimeric antigen receptor T cell; CNS, central nervous system; CR, complete remission; CRS, cytokine releasing syndrome; DLT, dose-limiting toxicity; EMD, extramedullary disease; ESC, dose escalation; EXP, dose expansion; Gr, grade; HR, high-risk; HSCT, hematopoietic stem cell transplantation; ICANS, immune effector cell-associated neurotoxicity syndrome; IMiDs, immunomodulatory drugs; IV, intravenous; MoAb, monoclonal antibody; MRD, minimal residual disease; NR, non-reached; ORR, overall (objective) response rate; PI, proteasome inhibitor; PR, partial response; RP2D, Recommended Phase 2 Dose; SAE, serious AE; SC, subcutaneous; TEAE, treatment emerged AE; Tx, treatment; URI, upper respiratory tract infection; VGPR, very good partial response.