Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy Trial of BNT411

Brief summary public domain (ClinicalTrials.gov)

This first-in-human (FIH) trial aimed to establish a safe dose of BNT411 as a monotherapy and in combination with atezolizumab, carboplatin and etoposide. BNT411 is a toll-like receptor 7 (TLR7) agonist which is expected to mount broad innate and adaptive immune reactions, especially in combination with cytotoxic therapies and immune checkpoint inhibitors.

Detailed description public domain (ClinicalTrials.gov)

The first part (Part 1A) of this trial was a FIH, open-label, dose-escalation trial studying BNT411 monotherapy in patients with different types of malignant solid tumors in order to determine the safety profile of BNT411. The second part (Part 1B) aimed to determine further the safety profile of BNT411 in combination with atezolizumab, carboplatin and etoposide in patients with chemotherapy-naïve ES-SCLC. The third part (Part 2) was the expansion phase to explore BNT411 further as a monotherapy or in combination with atezolizumab, carboplatin and etoposide in select tumor indications. Different treatment schedules and other indications were planned to be explored in Part 2 of this trial, however, the sponsor decided not to continue with this part of this trial.

Posted results (ClinicalTrials.gov registry) · primary outcome public domain (ClinicalTrials.gov)

Number of Participants With Dose Limiting Toxicities (DLTs) [Cycle 1 (21 Days)]. Count Of Participants, Participants. Part 1A: BNT411 Monotherapy: DL1: 0.05 mcg/kg (n=2): 0; Part 1A: BNT411 Monotherapy: DL2: 0.15 mcg/kg (n=1): 0; Part 1A: BNT411 Monotherapy: DL3: 0.45 mcg/kg (n=1): 0; Part 1A: BNT411 Monotherapy: DL4: 1.2 mcg/kg (n=3): 0; Part 1A: BNT411 Monotherapy: DL5: 2.4 mcg/kg (n=3): 0; Part 1A: BNT411 Monotherapy: DL6: 4.8 mcg/kg (n=10): 0; Part 1A: BNT411 Monotherapy: DL6_2i: 6.0 mcg/kg (n=6): 0; Part 1A: BNT411 Monotherapy: DL6_1i: 7.2 mcg/kg (n=6): 2; Part 1A: BNT411 Monotherapy: DL7: 9.6 mcg/kg (n=5): 2; Part 1B: BNT411 Combination Dose: DL4: 1.2 mcg/kg (n=2): 0; Part 1B: BNT411 Combination Dose: DL5: 2.4 mcg/kg (n=3): 0.

Posted results (ClinicalTrials.gov registry) · primary outcome public domain (ClinicalTrials.gov)

Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (TESAEs) and Grade >=3 TEAEs [From Baseline until 60 days after last dose of study treatment (3 years and 11 months)]. Count Of Participants, Participants. TEAE: Part 1A: BNT411 Monotherapy: DL1: 0.05 mcg/kg (n=2): 2; Part 1A: BNT411 Monotherapy: DL2: 0.15 mcg/kg (n=1): 1; Part 1A: BNT411 Monotherapy: DL3: 0.45 mcg/kg (n=1): 1; Part 1A: BNT411 Monotherapy: DL4: 1.2 mcg/kg (n=3): 3; Part 1A: BNT411 Monotherapy: DL5: 2.4 mcg/kg (n=4): 4; Part 1A: BNT411 Monotherapy: DL6: 4.8 mcg/kg (n=14): 14; Part 1A: BNT411 Monotherapy: DL6_2i: 6.0 mcg/kg (n=8): 8; Part 1A: BNT411 Monotherapy: DL6_1i: 7.2 mcg/kg (n=6): 6; Part 1A: BNT411 Monotherapy: DL7: 9.6 mcg/kg (n=6): 6; Part 1B: BNT411 Combination Dose: DL4: 1.2 mcg/kg (n=3): 3; Part 1B: BNT411 Combination Dose: DL5: 2.4 mcg/kg (n=4): 4. Related TEAE: Part 1A: BNT411 Monotherapy: DL1: 0.05 mcg/kg (n=2): 2; Part 1A: BNT411 Monotherapy: DL2: 0.15 mcg/kg (n=1): 1; Part 1A: BNT411 Monotherapy: DL3: 0.45 mcg/kg (n=1): 0; Part 1A: BNT411 Monotherapy: DL4: 1.2 mcg/kg (n=3): 2; Part 1A: BNT411 Monotherapy: DL5: 2.4 mcg/kg (n=4): 1; Part 1A: BNT411 Monotherapy: DL6: 4.8 mcg/kg (n=14): 13; Part 1A: BNT411 Monotherapy: DL6_2i: 6.0 mcg/kg (n=8): 7; Part 1A: BNT411 Monotherapy: DL6_1i: 7.2 mcg/kg (n=6): 6; Part 1A: BNT411 Monotherapy: DL7: 9.6 mcg/kg (n=6): 6; Part 1B: BNT411 Combination Dose: DL4: 1.2 mcg/kg (n=3): 3; Part 1B: BNT411 Combination Dose: DL5: 2.4 mcg/kg (n=4): 4. Grade >=3 TEAE: Part 1A: BNT411 Monotherapy: DL1: 0.05 mcg/kg (n=2): 1; Part 1A: BNT411 Monotherapy: DL2: 0.15 mcg/kg (n=1): 0; Part 1A: BNT411 Monotherapy: DL3: 0.45 mcg/kg (n=1): 1; Part 1A: BNT411 Monotherapy: DL4: 1.2 mcg/kg (n=3): 0; Part 1A: BNT411 Monotherapy: DL5: 2.4 mcg/kg (n=4): 3; Part 1A: BNT411 Monotherapy: DL6: 4.8 mcg/kg (n=14): 3; Part 1A: BNT411 Monotherapy: DL6_2i: 6.0 mcg/kg (n=8): 3; Part 1A: BNT411 Monotherapy: DL6_1i: 7.2 mcg/kg (n=6): 5; Part 1A: BNT411 Monotherapy: DL7: 9.6 mcg/kg (n=6): 5; Part 1B: BNT411 Combination Dose: DL4: 1.2 mcg/kg (n=3): 3; Part 1B: BNT411 Combination Dose: DL5: 2.4 mcg/kg (n=4): 3. Related Grade >=3 TEAE: Part 1A: BNT411 Monotherapy: DL1: 0.05 mcg/kg (n=2): 0; Part 1A: BNT411 Monotherapy: DL2: 0.15 mcg/kg (n=1): 0; Part 1A: BNT411 Monotherapy: DL3: 0.45 mcg/kg (n=1): 0; Part 1A: BNT411 Monotherapy: DL4: 1.2 mcg/kg (n=3): 0; Part 1A: BNT411 Monotherapy: DL5: 2.4 mcg/kg (n=4): 0; Part 1A: BNT411 Monotherapy: DL6: 4.8 mcg/kg (n=14): 2; Part 1A: BNT411 Monotherapy: DL6_2i: 6.0 mcg/kg (n=8): 2; Part 1A: BNT411 Monotherapy: DL6_1i: 7.2 mcg/kg (n=6): 3; Part 1A: BNT411 Monotherapy: DL7: 9.6 mcg/kg (n=6): 5; Part 1B: BNT411 Combination Dose: DL4: 1.2 mcg/kg (n=3): 3; Part 1B: BNT411 Combination Dose: DL5: 2.4 mcg/kg (n=4): 3. TESAE: Part 1A: BNT411 Monotherapy: DL1: 0.05 mcg/kg (n=2): 1; Part 1A: BNT411 Monotherapy: DL2: 0.15 mcg/kg (n=1): 0; Part 1A: BNT411 Monotherapy: DL3: 0.45 mcg/kg (n=1): 1; Part 1A: BNT411 Monoth

Posted results (ClinicalTrials.gov registry) · primary outcome public domain (ClinicalTrials.gov)

Number of Participants Reporting Dose Reduction and/or Discontinuation of BNT411 Due to TEAEs [From Baseline until 60 days after last dose of study treatment (3 years and 11 months)]. Count Of Participants, Participants. Dose Reduction of BNT411: Part 1A: BNT411 Monotherapy: DL1: 0.05 mcg/kg (n=2): 0; Part 1A: BNT411 Monotherapy: DL2: 0.15 mcg/kg (n=1): 0; Part 1A: BNT411 Monotherapy: DL3: 0.45 mcg/kg (n=1): 0; Part 1A: BNT411 Monotherapy: DL4: 1.2 mcg/kg (n=3): 0; Part 1A: BNT411 Monotherapy: DL5: 2.4 mcg/kg (n=4): 0; Part 1A: BNT411 Monotherapy: DL6: 4.8 mcg/kg (n=14): 1; Part 1A: BNT411 Monotherapy: DL6_2i: 6.0 mcg/kg (n=8): 1; Part 1A: BNT411 Monotherapy: DL6_1i: 7.2 mcg/kg (n=6): 3; Part 1A: BNT411 Monotherapy: DL7: 9.6 mcg/kg (n=6): 3; Part 1B: BNT411 Combination Dose: DL4: 1.2 mcg/kg (n=3): 0; Part 1B: BNT411 Combination Dose: DL5: 2.4 mcg/kg (n=4): 0. Discontinuation of BNT411 due to TEAEs: Part 1A: BNT411 Monotherapy: DL1: 0.05 mcg/kg (n=2): 1; Part 1A: BNT411 Monotherapy: DL2: 0.15 mcg/kg (n=1): 0; Part 1A: BNT411 Monotherapy: DL3: 0.45 mcg/kg (n=1): 1; Part 1A: BNT411 Monotherapy: DL4: 1.2 mcg/kg (n=3): 0; Part 1A: BNT411 Monotherapy: DL5: 2.4 mcg/kg (n=4): 0; Part 1A: BNT411 Monotherapy: DL6: 4.8 mcg/kg (n=14): 1; Part 1A: BNT411 Monotherapy: DL6_2i: 6.0 mcg/kg (n=8): 1; Part 1A: BNT411 Monotherapy: DL6_1i: 7.2 mcg/kg (n=6): 1; Part 1A: BNT411 Monotherapy: DL7: 9.6 mcg/kg (n=6): 0; Part 1B: BNT411 Combination Dose: DL4: 1.2 mcg/kg (n=3): 1; Part 1B: BNT411 Combination Dose: DL5: 2.4 mcg/kg (n=4): 3.

Posted results (ClinicalTrials.gov registry) · primary outcome public domain (ClinicalTrials.gov)

Maximal Tolerated Dose (MTD) of BNT411 [Cycle 1 (21 days)]. Number, microgram/kilogram (mcg/kg). All Participants (n=42): 6.0.

Posted results (ClinicalTrials.gov registry) · primary outcome public domain (ClinicalTrials.gov)

Recommended Phase 2 Dose (RP2D) of BNT411 [Cycle 1 (21 days)]. Number, microgram/kilogram (mcg/kg). All Participants (n=42): 4.8.

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Pharmacokinetics (PK) Assessment for BNT411: Area Under the Concentration Time Curve (AUC0-last) [Part 1A: Cycle 1 Day 1; Cycle 2 Day 1; Part 1B: Cycle 1 Day 2; Cycle 2 Day 2 (each cycle duration=21 days)]. Mean, hours (h)*picogram (pg)/milliliters (mL) (Standard Deviation). Cycle 1 Day 1: Part 1A: BNT411 Monotherapy: DL1: 0.05 mcg/kg (n=2): 187.3477 (NA) [Standard deviation could not be calculated as only 1 participant was available for the analysis.]; Part 1A: BNT411 Monotherapy: DL2: 0.15 mcg/kg (n=1): 1477.6656 (NA) [Standard deviation could not be calculated as only 1 participant was available for the analysis.]; Part 1A: BNT411 Monotherapy: DL3: 0.45 mcg/kg (n=1): 3123.7583 (NA) [Standard deviation could not be calculated as only 1 participant was available for the analysis.]; Part 1A: BNT411 Monotherapy: DL4: 1.2 mcg/kg (n=3): 4724.5276 (3433.94480); Part 1A: BNT411 Monotherapy: DL5: 2.4 mcg/kg (n=4): 9445.2536 (3902.75812); Part 1A: BNT411 Monotherapy: DL6: 4.8 mcg/kg (n=14): 18735.9783 (11750.72661); Part 1A: BNT411 Monotherapy: DL6_2i: 6.0 mcg/kg (n=7): 22365.2916 (8763.37410); Part 1A: BNT411 Monotherapy: DL6_1i: 7.2 mcg/kg (n=6): 49384.9308 (31393.75269); Part 1A: BNT411 Monotherapy: DL7: 9.6 mcg/kg (n=6): 29680.3554 (12850.18934). Cycle 2 Day 1: Part 1A: BNT411 Monotherapy: DL1: 0.05 mcg/kg (n=2): 327.1261 (143.16329); Part 1A: BNT411 Monotherapy: DL2: 0.15 mcg/kg (n=1): 3341.8368 (NA) [Standard deviation could not be calculated as only 1 participant was available for the analysis.]; Part 1A: BNT411 Monotherapy: DL3: 0.45 mcg/kg (n=1): 2313.8369 (NA) [Standard deviation could not be calculated as only 1 participant was available for the analysis.]; Part 1A: BNT411 Monotherapy: DL4: 1.2 mcg/kg (n=3): 4635.3150 (3330.49325); Part 1A: BNT411 Monotherapy: DL5: 2.4 mcg/kg (n=4): 11745.1614 (2871.09499); Part 1A: BNT411 Monotherapy: DL6: 4.8 mcg/kg (n=14): 20998.2267 (11223.40206); Part 1A: BNT411 Monotherapy: DL6_2i: 6.0 mcg/kg (n=7): 18392.6594 (7546.26734); Part 1A: BNT411 Monotherapy: DL6_1i: 7.2 mcg/kg (n=6): 26266.1125 (18091.16303); Part 1A: BNT411 Monotherapy: DL7: 9.6 mcg/kg (n=6): 28693.3094 (7377.64393). Cycle 1 Day 2: Part 1B: BNT411 Combination Dose: DL4: 1.2 mcg/kg (n=3): 3604.2235 (1804.20847); Part 1B: BNT411 Combination Dose: DL5: 2.4 mcg/kg (n=4): 6258.0743 (1565.55574). Cycle 2 Day 2: Part 1B: BNT411 Combination Dose: DL4: 1.2 mcg/kg (n=3): 3543.6926 (4508.63205); Part 1B: BNT411 Combination Dose: DL5: 2.4 mcg/kg (n=4): 3369.5271 (NA) [Standard deviation could not be calculated as only 1 participant was available for the analysis.].

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

PK Assessment for BNT411: Clearance (CL) [Part 1A: Cycle 1 Day 1; Cycle 2 Day 1; Part 1B: Cycle 1 Day 2; Cycle 2 Day 2 (each cycle duration=21 days)]. Mean, liters (L)/hours (h) (Standard Deviation). Cycle 1 Day 1: Part 1A: BNT411 Monotherapy: DL1: 0.05 mcg/kg (n=1): 27.6502 (NA) [Standard deviation could not be calculated as only 1 participant was available for the analysis.]; Part 1A: BNT411 Monotherapy: DL2: 0.15 mcg/kg (n=1): 8.3063 (NA) [Standard deviation could not be calculated as only 1 participant was available for the analysis.]; Part 1A: BNT411 Monotherapy: DL3: 0.45 mcg/kg (n=1): 13.1362 (NA) [Standard deviation could not be calculated as only 1 participant was available for the analysis.]; Part 1A: BNT411 Monotherapy: DL4: 1.2 mcg/kg (n=3): 36.6351 (34.63090); Part 1A: BNT411 Monotherapy: DL5:2.4 mcg/kg (n=4): 21.1677 (8.41500); Part 1A: BNT411 Monotherapy: DL6: 4.8 mcg/kg (n=14): 23.6285 (9.44317); Part 1A: BNT411 Monotherapy: DL6_2i: 6.0 mcg/kg (n=7): 24.7574 (24.89704); Part 1A: BNT411 Monotherapy: DL6_1i: 7.2 mcg/kg (n=5): 13.4479 (6.36326); Part 1A: BNT411 Monotherapy: DL7: 9.6 mcg/kg (n=6): 24.4680 (9.09568). Cycle 2 Day 1: Part 1A: BNT411 Monotherapy: DL2: 0.15 mcg/kg (n=1): 3.5213 (NA) [Standard deviation could not be calculated as only 1 participant was available for the analysis.]; Part 1A: BNT411 Monotherapy: DL3: 0.45 mcg/kg (n=1): 17.6849 (NA) [Standard deviation could not be calculated as only 1 participant was available for the analysis.]; Part 1A: BNT411 Monotherapy: DL4: 1.2 mcg/kg (n=3): 28.0090 (14.49788); Part 1A: BNT411 Monotherapy: DL5:2.4 mcg/kg (n=4): 13.9638 (2.28039); Part 1A: BNT411 Monotherapy: DL6: 4.8 mcg/kg (n=14): 22.2684 (13.53332); Part 1A: BNT411 Monotherapy: DL6_2i: 6.0 mcg/kg (n=7): 25.7574 (14.62545); Part 1A: BNT411 Monotherapy: DL6_1i: 7.2 mcg/kg (n=5): 20.8883 (3.90723); Part 1A: BNT411 Monotherapy: DL7: 9.6 mcg/kg (n=6): 21.9203 (10.72759). Cycle 1 Day 2: Part 1B: BNT411 Combination Dose: DL4: 1.2 mcg/kg (n=2): 20.5762 (10.33093); Part 1B: BNT411 Combination Dose: DL5: 2.4 mcg/k (n=4): 30.8326 (5.92557). Cycle 2 Day 2: Part 1B: BNT411 Combination Dose: DL4: 1.2 mcg/kg (n=2): 14.3209 (NA) [Standard deviation could not be calculated as only 1 participant was available for the analysis.]; Part 1B: BNT411 Combination Dose: DL5: 2.4 mcg/k (n=4): 38.3186 (NA) [Standard deviation could not be calculated as only 1 participant was available for the analysis.].

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

PK Assessment for BNT411: Volume of Distribution (Vd) [Part 1A: Cycle 1 Day 1; Cycle 2 Day 1; Part 1B: Cycle 1 Day 2; Cycle 2 Day 2 (each cycle duration=21 days)]. Mean, liters (L) (Standard Deviation). Cycle 1 Day 1: Part 1A: BNT411 Monotherapy: DL1: 0.05 mcg/kg (n=1): 75.5414 (NA) [Standard deviation could not be calculated as only 1 participant was available for the analysis.]; Part 1A: BNT411 Monotherapy: DL2: 0.15 mcg/kg (n=1): 47.0697 (NA) [Standard deviation could not be calculated as only 1 participant was available for the analysis.]; Part 1A: BNT411 Monotherapy: DL3: 0.45 mcg/kg (n=1): 108.1691 (NA) [Standard deviation could not be calculated as only 1 participant was available for the analysis.]; Part 1A: BNT411 Monotherapy: DL4: 1.2 mcg/kg (n=3): 296.6890 (313.18628); Part 1A: BNT411 Monotherapy: DL5: 2.4 mcg/kg (n=4): 220.7140 (74.05373); Part 1A: BNT411 Monotherapy: DL6: 4.8 mcg/kg (n=14): 232.0475 (100.19550); Part 1A: BNT411 Monotherapy: DL6_2i: 6.0 mcg/kg (n=7): 168.7668 (145.45978); Part 1A: BNT411 Monotherapy: DL6_1i: 7.2 mcg/kg (n=5): 156.7781 (77.21878); Part 1A: BNT411 Monotherapy: DL7: 9.6 mcg/kg (n=6): 222.3040 (85.88236). Cycle 2 Day 1: Part 1A: BNT411 Monotherapy: DL2: 0.15 mcg/kg (n=1): 18.6963 (NA) [Standard deviation could not be calculated as only 1 participant was available for the analysis.]; Part 1A: BNT411 Monotherapy: DL3: 0.45 mcg/kg (n=1): 159.4620 (NA) [Standard deviation could not be calculated as only 1 participant was available for the analysis.]; Part 1A: BNT411 Monotherapy: DL4: 1.2 mcg/kg (n=3): 194.0698 (97.37669); Part 1A: BNT411 Monotherapy: DL5: 2.4 mcg/kg (n=4): 127.2646 (21.21154); Part 1A: BNT411 Monotherapy: DL6: 4.8 mcg/kg (n=14): 187.7812 (96.09022); Part 1A: BNT411 Monotherapy: DL6_2i: 6.0 mcg/kg (n=7): 163.0226 (44.35908); Part 1A: BNT411 Monotherapy: DL6_1i: 7.2 mcg/kg (n=5): 186.4341 (31.41644); Part 1A: BNT411 Monotherapy: DL7: 9.6 mcg/kg (n=6): 148.4863 (125.70109). Cycle 1 Day 2: Part 1B: BNT411 Combination Dose: DL4: 1.2 mcg/kg (n=2): 132.8456 (22.90794); Part 1B: BNT411 Combination Dose: DL5: 2.4 mcg/kg (n=4): 205.7365 (14.86844). Cycle 2 Day 2: Part 1B: BNT411 Combination Dose: DL4: 1.2 mcg/kg (n=2): 125.7815 (NA) [Standard deviation could not be calculated as only 1 participant was available for the analysis.]; Part 1B: BNT411 Combination Dose: DL5: 2.4 mcg/kg (n=4): 243.8492 (NA) [Standard deviation could not be calculated as only 1 participant was available for the analysis.].

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

PK Assessment for BNT411: Maximum Plasma Concentration (Cmax) [Part 1A: Cycle 1 Day 1; Cycle 2 Day 1; Part 1B: Cycle 1 Day 2; Cycle 2 Day 2 (each cycle duration=21 days)]. Mean, picogram/milliliters (pg/mL) (Standard Deviation). Cycle 1 Day 1: Part 1A: BNT411 Monotherapy: DL1: 0.05 mcg/kg (n=2): 152.0 (NA) [Standard deviation could not be calculated as only 1 participant was available for the analysis.]; Part 1A: BNT411 Monotherapy: DL2: 0.15 mcg/kg (n=1): 1020.0 (NA) [Standard deviation could not be calculated as only 1 participant was available for the analysis.]; Part 1A: BNT411 Monotherapy: DL3: 0.45 mcg/kg (n=1): 2437.0 (NA) [Standard deviation could not be calculated as only 1 participant was available for the analysis.]; Part 1A: BNT411 Monotherapy: DL4: 1.2 mcg/kg (n=3): 3229.3 (1847.84); Part 1A: BNT411 Monotherapy: DL5: 2.4 mcg/kg (n=4): 8191.3 (3211.56); Part 1A: BNT411 Monotherapy: DL6: 4.8 mcg/kg (n=14): 13005.9 (4681.33); Part 1A: BNT411 Monotherapy: DL6_2i: 6.0 mcg/kg (n=7): 20404.6 (8137.20); Part 1A: BNT411 Monotherapy: DL6_1i: 7.2 mcg/kg (n=6): 31596.8 (10260.05); Part 1A: BNT411 Monotherapy: DL7: 9.6 mcg/kg (n=6): 25967.7 (10270.43). Cycle 2 Day 1: Part 1A: BNT411 Monotherapy: DL1: 0.05 mcg/kg (n=2): 254.0 (57.98); Part 1A: BNT411 Monotherapy: DL2: 0.15 mcg/kg (n=1): 2163.0 (NA) [Standard deviation could not be calculated as only 1 participant was available for the analysis.]; Part 1A: BNT411 Monotherapy: DL3: 0.45 mcg/kg (n=1): 1520.0 (NA) [Standard deviation could not be calculated as only 1 participant was available for the analysis.]; Part 1A: BNT411 Monotherapy: DL4: 1.2 mcg/kg (n=3): 2947.3 (1281.14); Part 1A: BNT411 Monotherapy: DL5: 2.4 mcg/kg (n=4): 8104.7 (1473.43); Part 1A: BNT411 Monotherapy: DL6: 4.8 mcg/kg (n=14): 14804.4 (6042.78); Part 1A: BNT411 Monotherapy: DL6_2i: 6.0 mcg/kg (n=7): 13800.0 (3642.80); Part 1A: BNT411 Monotherapy: DL6_1i: 7.2 mcg/kg (n=6): 19551.8 (16904.30); Part 1A: BNT411 Monotherapy: DL7: 9.6 mcg/kg (n=6): 22547.8 (7933.89). Cycle 1 Day 2: Part 1B: BNT411 Combination Dose: DL4: 1.2 mcg/kg (n=3): 2880.33 (2065.462); Part 1B: BNT411 Combination Dose: DL5: 2.4 mcg/kg (n=4): 5598.25 (766.713). Cycle 2 Day 2: Part 1B: BNT411 Combination Dose: DL4: 1.2 mcg/kg (n=3): 2993.95 (4214.427); Part 1B: BNT411 Combination Dose: DL5: 2.4 mcg/kg (n=4): 2900.00 (NA) [Standard deviation could not be calculated as only 1 participant was available for the analysis.].

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

PK Assessment for BNT411: Time to Reach Cmax (Tmax) [Part 1A: Cycle 1 Day 1; Cycle 2 Day 1; Part 1B: Cycle 1 Day 2; Cycle 2 Day 2 (each cycle duration=21 days)]. Median, hours (h) (Full Range). Cycle 1 Day 1: Part 1A: BNT411 Monotherapy: DL1: 0.05 mcg/kg (n=2): 0.7667 (NA to NA) [Full range could not be calculated as only 1 participant was available for the analysis.]; Part 1A: BNT411 Monotherapy: DL2: 0.15 mcg/kg (n=1): 0.5000 (0.500 to 0.500); Part 1A: BNT411 Monotherapy: DL3: 0.45 mcg/kg (n=1): 0.5667 (NA to NA) [Full range could not be calculated as only 1 participant was available for the analysis.]; Part 1A: BNT411 Monotherapy: DL4: 1.2 mcg/kg (n=3): 0.6500 (0.533 to 0.683); Part 1A: BNT411 Monotherapy: DL5: 2.4 mcg/kg (n=4): 0.5417 (0.500 to 0.600); Part 1A: BNT411 Monotherapy: DL6: 4.8 mcg/kg (n=14): 0.5917 (0.500 to 0.867); Part 1A: BNT411 Monotherapy: DL6_2i: 6.0 mcg/kg (n=7): 0.6000 (0.550 to 0.700); Part 1A: BNT411 Monotherapy: DL6_1i: 7.2 mcg/kg (n=6): 0.5417 (0.500 to 0.717); Part 1A: BNT411 Monotherapy: DL7: 9.6 mcg/kg (n=6): 0.6000 (0.500 to 0.667). Cycle 2 Day 1: Part 1A: BNT411 Monotherapy: DL1: 0.05 mcg/kg (n=2): 0.5750 (0.567 to 0.583); Part 1A: BNT411 Monotherapy: DL2: 0.15 mcg/kg (n=1): 0.5000 (0.500 to 0.500); Part 1A: BNT411 Monotherapy: DL3: 0.45 mcg/kg (n=1): 0.5833 (NA to NA) [Full range could not be calculated as only 1 participant was available for the analysis.]; Part 1A: BNT411 Monotherapy: DL4: 1.2 mcg/kg (n=3): 0.5833 (0.583 to 0.700); Part 1A: BNT411 Monotherapy: DL5: 2.4 mcg/kg (n=4): 0.5000 (0.500 to 0.583); Part 1A: BNT411 Monotherapy: DL6: 4.8 mcg/kg (n=14): 0.6000 (0.500 to 0.817); Part 1A: BNT411 Monotherapy: DL6_2i: 6.0 mcg/kg (n=7): 0.6167 (0.583 to 0.617); Part 1A: BNT411 Monotherapy: DL6_1i: 7.2 mcg/kg (n=6): 0.6333 (0.567 to 0.667); Part 1A: BNT411 Monotherapy: DL7: 9.6 mcg/kg (n=6): 0.6417 (0.600 to 0.750). Cycle 1 Day 2: Part 1B: BNT411 Combination Dose: DL4: 1.2 mcg/kg (n=3): 0.5833 (0.500 to 1.017); Part 1B: BNT411 Combination Dose: DL5: 2.4 mcg/kg (n=4): 0.6000 (0.500 to 0.850). Cycle 2 Day 2: Part 1B: BNT411 Combination Dose: DL4: 1.2 mcg/kg (n=3): 13.1083 (0.633 to 25.583); Part 1B: BNT411 Combination Dose: DL5: 2.4 mcg/kg (n=4): 0.5833 (NA to NA) [Full range could not be calculated as only 1 participant was available for the analysis.].

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

PK Assessment for BNT411: Trough Concentration (Ctrough) [Part 1A: Start of infusion on Cycle 1 Day 8, Day 15, Day 22, Day 43; Day 85; Part 1B: Start of infusion on Cycle 1 Day 8, Day 15, Day 23, Day 44 (each cycle duration=21 days)]. Mean, picogram/milliliters (pg/mL) (Standard Deviation). Cycle 1 Day 8: Part 1A: BNT411 Monotherapy: DL1: 0.05 mcg/kg (n=2): 0.000 (NA) [Standard deviation could not be calculated as only 1 participant was available for the analysis.]; Part 1A: BNT411 Monotherapy: DL2: 0.15 mcg/kg (n=1): 0.000 (NA) [Standard deviation could not be calculated as only 1 participant was available for the analysis.]; Part 1A: BNT411 Monotherapy: DL3: 0.45 mcg/kg (n=1): 0.000 (NA) [Standard deviation could not be calculated as only 1 participant was available for the analysis.]; Part 1A: BNT411 Monotherapy: DL4: 1.2 mcg/kg (n=3): 0.000 (0.0000); Part 1A: BNT411 Monotherapy: DL5: 2.4 mcg/kg (n=4): 0.000 (NA) [Standard deviation could not be calculated as only 1 participant was available for the analysis.]; Part 1A: BNT411 Monotherapy: DL6: 4.8 mcg/kg (n=8): 0.476 (0.9789); Part 1A: BNT411 Monotherapy: DL6_2i: 6.0 mcg/kg (n=6): 0.000 (0.0000); Part 1A: BNT411 Monotherapy: DL6_1i: 7.2 mcg/kg (n=2): 0.000 (0.0000); Part 1A: BNT411 Monotherapy: DL7: 9.6 mcg/kg (n=4): 0.000 (0.0000); Part 1B: BNT411 Combination Dose: DL4: 1.2 mcg/kg (n=2): 0.0 (0.00); Part 1B: BNT411 Combination Dose: DL5: 2.4 mcg/kg (n=4): 0.0 (NA) [Standard deviation could not be calculated as only 1 participant was available for the analysis.]. Cycle 1 Day 15: Part 1A: BNT411 Monotherapy: DL1: 0.05 mcg/kg (n=2): 8.400 (11.8794); Part 1A: BNT411 Monotherapy: DL3: 0.45 mcg/kg (n=1): 0.000 (NA) [Standard deviation could not be calculated as only 1 participant was available for the analysis.]; Part 1A: BNT411 Monotherapy: DL4: 1.2 mcg/kg (n=3): 0.000 (0.0000); Part 1A: BNT411 Monotherapy: DL5: 2.4 mcg/kg (n=4): 0.253 (0.5050); Part 1A: BNT411 Monotherapy: DL6: 4.8 mcg/kg (n=8): 0.168 (0.4123); Part 1A: BNT411 Monotherapy: DL6_2i: 6.0 mcg/kg (n=6): 0.580 (0.6722); Part 1A: BNT411 Monotherapy: DL6_1i: 7.2 mcg/kg (n=2): 1.350 (0.2970); Part 1A: BNT411 Monotherapy: DL7: 9.6 mcg/kg (n=4): 1.655 (0.5303); Part 1B: BNT411 Combination Dose: DL4: 1.2 mcg/kg (n=2): 0.0 (NA) [Standard deviation could not be calculated as only 1 participant was available for the analysis.]; Part 1B: BNT411 Combination Dose: DL5: 2.4 mcg/kg (n=4): 0.0 (0.00). Cycle 1 Day 22: Part 1A: BNT411 Monotherapy: DL1: 0.05 mcg/kg (n=2): 0.000 (0.0000); Part 1A: BNT411 Monotherapy: DL3: 0.45 mcg/kg (n=1): 0.000 (NA) [Standard deviation could not be calculated as only 1 participant was available for the analysis.]; Part 1A: BNT411 Monotherapy: DL4: 1.2 mcg/kg (n=3): 51.500 (72.8320); Part 1A: BNT411 Monotherapy: DL5: 2.4 mcg/kg (n=4): 0.000 (0.0000); Part 1A: BNT411 Monotherapy: DL6: 4.8 mcg/kg (n=8): 0.000 (0.0000); Part 1A: BNT411 Monotherapy: DL6_2i: 6.0 mcg/kg (n=6): 0.000 (0.0000); Part 1A: BNT411 Monotherapy: DL6

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

PK Assessment for BNT411: Terminal Elimination Half-life (T1/2) [Part 1A: Cycle 1 Day 1; Cycle 2 Day 1; Part 1B: Cycle 1 Day 2; Cycle 2 Day 2 (each cycle duration=21 days)]. Mean, hours (h) (Standard Deviation). Cycle 1 Day 1: Part 1A: BNT411 Monotherapy: DL1: 0.05 mcg/kg (n=1): 1.8937 (NA) [Standard deviation could not be calculated as only 1 participant was available for the analysis.]; Part 1A: BNT411 Monotherapy: DL2: 0.15 mcg/kg (n=1): 3.9279 (NA) [Standard deviation could not be calculated as only 1 participant was available for the analysis.]; Part 1A: BNT411 Monotherapy: DL3: 0.45 mcg/kg (n=1): 5.7077 (NA) [Standard deviation could not be calculated as only 1 participant was available for the analysis.]; Part 1A: BNT411 Monotherapy: DL4: 1.2 mcg/kg (n=3): 5.2525 (0.99582); Part 1A: BNT411 Monotherapy: DL5: 2.4 mcg/kg (n=4): 7.4679 (1.87347); Part 1A: BNT411 Monotherapy: DL6: 4.8 mcg/kg (n=14): 7.4600 (4.30673); Part 1A: BNT411 Monotherapy: DL6_2i: 6.0 mcg/kg (n=7): 5.1189 (1.23014); Part 1A: BNT411 Monotherapy: DL6_1i: 7.2 mcg/kg (n=5): 8.7346 (4.71577); Part 1A: BNT411 Monotherapy: DL7: 9.6 mcg/kg (n=6): 6.2721 (0.48131). Cycle 2 Day 1: Part 1A: BNT411 Monotherapy: DL2: 0.15 mcg/kg (n=1): 3.6803 (NA) [Standard deviation could not be calculated as only 1 participant was available for the analysis.]; Part 1A: BNT411 Monotherapy: DL3: 0.45 mcg/kg (n=1): 6.2500 (NA) [Standard deviation could not be calculated as only 1 participant was available for the analysis.]; Part 1A: BNT411 Monotherapy: DL4: 1.2 mcg/kg (n=3): 4.9020 (0.57744); Part 1A: BNT411 Monotherapy: DL5: 2.4 mcg/kg (n=4): 6.3386 (0.73577); Part 1A: BNT411 Monotherapy: DL6: 4.8 mcg/kg (n=14): 6.0603 (1.18916); Part 1A: BNT411 Monotherapy: DL6_2i: 6.0 mcg/kg (n=7): 4.9479 (1.51079); Part 1A: BNT411 Monotherapy: DL6_1i: 7.2 mcg/kg (n=5): 6.2166 (0.45957); Part 1A: BNT411 Monotherapy: DL7: 9.6 mcg/kg (n=6): 4.5667 (2.07892). Cycle 1 Day 2: Part 1B: BNT411 Combination Dose: DL4: 1.2 mcg/kg (n=2): 4.8989 (1.68795); Part 1B: BNT411 Combination Dose: DL5: 2.4 mcg/kg (n=4): 4.7244 (0.68988). Cycle 2 Day 2: Part 1B: BNT411 Combination Dose: DL4: 1.2 mcg/kg (n=2): 6.0880 (NA) [Standard deviation could not be calculated as only 1 participant was available for the analysis.]; Part 1B: BNT411 Combination Dose: DL5: 2.4 mcg/kg (n=4): 4.4110 (NA) [Standard deviation could not be calculated as only 1 participant was available for the analysis.].