Tevimbra
tislelizumab
Species
Monkey
Longest study
13 wk
Genotox
Not conducted Not conducted
Carcinogenicity
Not conducted Not conducted
Repro
Conducted Conducted
First dose
Not conducted Not stated publicly
Speciesopen answer page →
Species
Cynomolgus monkey only
“The toxicity of tislelizumab was assessed in several studies in cynomolgus monkeys, the relevant species.”
Why that species
Binds human and cynomolgus PD-1 but not murine PD-1
“From the results shown, tislelizumab seems to specifically bind to PD-1 (and to cynomolgus PD-1, but not to murine PD-1) with KD in the order of 0.1-0.2 nM.”
Surrogate molecule
No surrogate; the clinical antibody was tested in cynomolgus monkey
“The toxicity of tislelizumab was assessed in several studies in cynomolgus monkeys, the relevant species.”
Study lengthopen answer page →
Longest pivotal study
13 weeks
“The Applicant performed a first repeat-dose toxicology study in monkeys (P14-057-CD), where 0/3/10/30 mg/kg tislelizumab was administered IV once biweekly for 13 weeks to 6 animals/sex/group followed by a 6-week recovery period”
Pivotal GLP studies
Cynomolgus monkey 13-week IV studies, 3-60 mg/kg every 2 weeks (7 doses)
“In repeat-dose toxicology studies in cynomolgus monkeys with intravenous dose administration for 13 weeks at doses of 3, 10, 30 or 60 mg/kg every 2 weeks for 13 weeks (7 dose administrations)”
Route in tox
IV; two single SC doses in males in the second study
“Doses of 0/30/60 mg/kg tislelizumab was administered IV once every two weeks for 13 weeks to 3 animals/sex/group or as two single doses (14 days apart to 3 males only) via subcutaneous injection (SQ).”
Skipped studiesopen answer page →
Genotoxicity
Not conducted (ICH S9)
“No studies have been performed to assess the potential of tislelizumab for carcinogenicity or genotoxicity in line with ICH guideline S9.”
Carcinogenicity
Not conducted (ICH S9)
“No studies have been performed to assess the potential of tislelizumab for carcinogenicity or genotoxicity in line with ICH guideline S9.”
Reproductive & developmental
No dedicated studies; PD-1/PD-L1 role in materno-fetal tolerance implies risk of abortion or stillbirth
“Given the role of the PD-1/PD-L1 pathway in maintaining materno-fetal tolerance, treatment with tislelizumab during pregnancy may lead to abortion or still births.”
Safety pharmacology
Incorporated into repeat-dose monkey studies; no respiratory, neural or cardiovascular effects
“Safety pharmacology parameters were incorporated in the toxicology studies and no effects were noted on parameters evaluating respiratory, neural or cardiovascular system.”
First doseopen answer page →
First-in-human starting dose
Not stated in public reviews
Why it's blank
The public FDA and EMA reviews of Tevimbra don't say how the first human dose was chosen. That rationale is in the IND, which is confidential, so it is missing for most approved products.
How it's usually set for monoclonal antibodies
ADCs with cytotoxic payloads follow the S9 rules (1/10 STD10 or 1/6 HNSTD of the ADC, scaled by body surface area). For immune agonists, a MABEL-based start dose should be considered instead.
“For example, for cytotoxic payloads, the starting clinical dose can be determined using either 1/10th the Severely Toxic Dose (STD) in 10% of animals (STD10) in rodents or 1/6th the Highest Non- Severely Toxic Dose (HNSTD) in non-rodents, for the ADC based on body surface area, depending on which is the most appropriate and/or sensitive species.”
This product's starting point
NOAEL / key findings: NOAEL 30 mg/kg Q2W, 4.3-6.6x human exposure at 200 mg; no treatment-related toxicity or histopathology (EMA assessment report, p. 30)
NOAEL / key findings
NOAEL 30 mg/kg Q2W, 4.3-6.6x human exposure at 200 mg; no treatment-related toxicity or histopathology
“no apparent treatment-related toxicity or histopathological changes were observed at doses up to 30 mg/kg every 2 weeks, corresponding to 4.3 to 6.6 times the exposure in humans with the clinical dose of 200 mg.”
Risksopen answer page →
Immune & cytokine safety
In vitro immunotoxicity/cytokine release assays: only neutralising ADA and possible enhanced recall response
“Beside the potential of tislelizumab to induce neutralising ADA and to possibly induce an enhanced recall response to the re-challenge antigen, no other toxicities were detected.”
Biodistribution & persistence
No specific tissue cross-reactivity in cynomolgus monkey or human tissues
“No specific tissue-cross reactivity with tislelizumab was noted in cynomolgus monkey or human tissues.”
Modality-specific risk
Increased infection severity and enhanced inflammatory responses from PD-1/PD-L1 blockade
“In animal models, inhibition of PD-L1/PD-1 signaling resulted in an increased severity of some infections and enhanced inflammatory responses.”