ESMO 2023 BioNTech Data
BNT211: Dose-Depend Increase in Adverse Events, Further Evaluation Ongoing
to Determine RP2D
Phase 1/2 FIH study (NCT04503278): Baseline characteristics and safety
Haanen J. et al. Presented at ESMO 2023. Abstract #LBA35.
Cohort
Patient baseline characteristics
DL0(n=2)
DL1 (n=4)
DL1+ CARVac (n=4)
DL2 (n=13)1
DL2+ CARVac (n=14)²
DL3 (n=7)
Total (n=44)
Age, years
55.5 (50-61)
54.5 (36-62)
1/1
3/1
51.0 (42-65)
2/2
45.0 (30-69)
7/6
48.0 (26-60)
50.5 (29-63)
8/6
4/3
48.0 (26-69)
25/19
Gender, male/female
Indication, n
Epithelial ovarian cancer (EOC)
1
1
2
6
Germ cell tumor (GCT)
1
Other indications³
0
3
1
1
5
2
563
232
17
16
CLDN6 2+/3+ cells, %
82.5 (80-85)
97.5 (80-100)
97.5 (50-100)
95.0 (80-100)
Prior treatment lines
3.0 (2-4)
4.0 (3-7)
4.0 (2-9)
4.0 (2-7)
100 (70-100)
4.0 (2-9)
80.0 (50-100)
3.5 (2-6)
11
95 (50-100)
4.0 (2-9)
Treatment and safety outcome
Duration of follow-up, days
321.5 (242-401)
44.5 (22-87)
90.5 (13-189)
71.5 (30-317)
120.5 (9-199)
90 (44-121)
94.5 (9-401)
CARVac injections4, n
ΝΑ
NA
3 (1-5)
ΝΑ
4 (1-7)
ΝΑ
4 (1-7)
Patients with TEAEs >G3 related to IMPS5, n
1
1
1
12
9
6
30
Patients with TESAES related to IMPs 6, n
1
0
0
4
4
5
14
Patients with DLTs7, n
0
0
0
1
2
1
4
Patients with CRS8, n
Patients with ICANS9, n
Deaths 10, n
1
0
0
2
6
9
LO
5
0
3
Data cut-off: 10 Sep 2023. 1 Cohort includes 3 patients dosed with 5x107 CAR-T. 2 Cohort includes 1 patient that did not reach full dose (2×107) and 1 patient treated that received full dose after 50% reduced lymphodepletion. 3 Other indications: 4 patients with lung cancer (different subtypes), 3 with desmoplastic round cell
tumors, 2 with esophageal cancer, 1 with endometrial carcinoma and 1 with sinonasal carcinoma. 4 Crossover of patients is not indicated, as option was enabled by safety review committee decision after dose decision for monotherapy cohort without impacting efficacy read out. 5 Most TEAES 2G3 were attributed to CAR-T
IMP (27/30). Most frequent TEAEs were laboratory findings (43.2%) including decreased blood cell counts, elevated liver function tests as well as levels of bilirubin and ferritin. Accordingly, cytopenia (25%) together with immune system (7%) and hepatobiliary disorders (5%) were reported frequently. 6 Most frequent non-
related TESAES were infections. 7 DLTs include 2 cases of pancytopenia, 1 case of hemophagocytic lymphohistiocytosis and 1 case of liver toxicity together with sepsis. 8 CRS was limited to G1-2 for 21/23 patients with 1 G3 and 1 G4 event. 9 Neurotoxicity was mild and self-limiting in 2 patients. 10 Most patient deaths
(11/12) were related to disease progression and 1 patient died from sepsis. Values given as median (range). CAR = chimeric antigen receptor; CLDN6 = claudin-6; CRS = cytokine release syndrome; DL = dose level; DLT = dose-limiting toxicity; G = Grade; ICANS immune effector cell-associated neurotoxicity syndrome;
IMP investigational medicinal product; TESAE treatment-emergent (serious) adverse event.
0
2
1
2
1
4
0
0
23
2
12
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