Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

ALL > ADCs > Flashcards

ADCs Flashcards

1
Q

How do you convert from HNSTD to a Ph 1 starting dose?

A

Divide HNSTD by 6 (NHPs) or 10 (rodents)

For HED (human equivalent dose), then divide by 3.1

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Mylotarg
(generic name, approval year, indication, target, payload, DAR, dose)

A

Gemtuzumab ozogamicin
2000 (CD33+ AML)
CD33
Calicheamicin
DAR 0-6 (average 2)
0.08 mg/kg

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Adcetris
(generic name, approval year, indication, target, payload, DAR, dose)

A

Brentuximab vedotin
2011 (HL, ALCL, PTCL)
CD30
MMAE
DAR 3-4 (average 3.2)
1.8 mg/kg

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Enhertu
(generic name, approval year, indication, target, payload, DAR, dose)

A

Trastuzumab deruxtecan
2019 (met and adj/neoadj breast, HER2-low breast; NSCLC, gastric/GEJ)
HER2
DXd
DAR 7-9 (average 7.7)
5.4 mg/kg

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

DatoDX
(generic name, approval year, indication, target, payload, DAR, dose)

A

Datopotamab deruxtecan
2024 (expected, DS/AZ)
TROP2
DXd
DAR 4
6 mg/kg

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Rank order ADCs for dose/cycle

A

Besponsa:
Mylotarg: 0.08 mg/kg
Zynlonta: 0.15 mg/kg
Padcev: 1.25 mg/kg
Polivy: 1.8 mg/kg
Adcetris: 1.8 mg/kg
Tivdak: 2 mg/kg
Kadcyla (T-DM1): 3.6 mg/kg
Enhertu: 5.4 mg/kg
DatoDx: 6 mg/kg

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Approved ADCs (target, payload, DAR)

3 DNA damaging agents
6 microtubule inhibitors
2 topo1 inhibitors

A

DNA damaging agents:
Besponsa (inotuzumab ozogamicin): CD22, calicheamicin, 6
Mylotarg (gemtuzumab ozogamicin): CD33, calicheamicin, 2-3
Zynlonta (loncastuximab tesirine): CD19, SGD199/PBD, 2.3

Microtubule inhibitors:
Polivy (polatuzumab vedotin): CD79b, MMAE, 3.5
Adcetris (brentuximab vedotin): CD30, MMAE, 4
Tivdak (tisotumab vedotin): TF, MMAE, 4
Padcev (enfortumab vedotin): Nectin4, MMAE, 3.8
Kadcyla (trastuzumab emtansine): HER2, DM1, 3.5
Blenrep (belantamab mafadotin): BCMA, MMAF/auristatin, 4

Topo1 inhibitors:
Enhertu (trastuzumab deruxtecan): HER2, DXd, 8
Trodelvy (sacituzumab govitecan): TROP2, SN-38 (camptothecin), 7.6
DatoDx (datopotamab deruxtecan): TROP2, DXd, 4

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Who are the two main CEACAM5 competitors?

A

M9140 (Merck-KGaA), glucuronidase cleavable linker, exatecan, DAR8, silent Fc

SAR445953 (Sanofi/Seagen/Pfizer), exatecan, DAR8

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Key highlights from M9140 at ASCO ‘24?

A
  • 40 pts treated (0.6-3.2 mg/kg)
  • Primarily heme tox
  • MTD was 2.8 mg/kg (2.4 and 2.8 mg/kg being taken forwarded into randomized expansion study)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What are HNSTDs demonstrated with SYNtecan-E ADCs?

A

30 mg/kg (IBI343, Claudin18-2-SYNtecanE)

50 mg/kg (MGC026, B7H3-SYNtecanE) - in Ph 1/2 dose escalation

90 mg/kg (IBI3001, bispecific B7H3/EGFR-SYNtecanE) - no clinical data

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What is IBI343?

What dose did IBI343 reach in Ph 1, and in which indications?

What dose is being planned for Ph 3?

A

Claudin18.2-SYNtecan-E from Innovent Biologics

10 mg/kg in GC/GEJ

Ph 3 trial is at 6 mg/kg

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What was reported about SAR’953 at ASCO ‘24?

A

No data reported yet, only study design: three-part Phase 1 trial with 410 patients. Part A is dose escalation, Part B is dose and schedule optimization (evaluating 2 schedules), and Part C is expansion cohorts in CRC, GC/GEJ, NSCLC (sq/non-sq), PDAC and SCLC.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What is MRG004A?

A

TF-ADC (Synaffix GC-HS with MMAE payload from Lepu Biopharma)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

How do you convert from mg/m2 to mg/kg?

A

Humans: divide by 37

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

How does exatecan compare to other TOPO1i?

A

Exatecan is a precursor to DXd, which is a more potent camptothecin (TOP1 inhibitor) analog relative to topotecan and irinotecan

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What is SN-38?

A

A TOPO1i, an active metabolite of irinotecan (1000x more potent than irinotecan)

17
Q

What is the difference between Kadcyla and Enhertu?

A

Kadcyla: trastuzumab-emtansine (DM1) (approved 2013). Approved for HER2+ mBC, and adjuvant HER2+ BC

Enhertu: trastuzumab-deruxtecan (DXd) (approved 2019) - in Ph 3, doubled 12-month PFS rate compared to Kadcyla (2021). Approved for mHER2+ (including HER2-low), NSCLC, GC/GEJ

18
Q

What are the main classes of ADC payloads?

A

Most potent:
- DNA damaging agents (PBD, calicheamicin)
- Microtubule inhibitorss (maytasine, auristatin)
- Topo I inhibitors (DXd, SN-38)

19
Q

What does self-immolative mean?

A

At low pH the linker will decompose and release free payload

20
Q

Which solid tumors are we going for with KIVU-107 and KIVU-305?

Which would likely already have received CPI?

A

NSCLC, CRC, gastric, PDAC, ovarian (we will try to enrol more CRC for KIVU-305)

NSCLC and gastric: all get CPI
CRC: only if MSI-hi
PDAC: rare unless on clinical trial

21
Q

What is the only other ADC (in addition to IBI343) that comes close to 6 mg/kg in humans?

What was the MTD for that ADC?

A

DS-1062 (TROP2, daiichi Sankyo, DXd, tetrapeptide-linker)

MTD 8 mg/kg (due to ILD signal), then moved forward with 6 mg/kg

22
Q

What is a potential MSI-hi artifact in CRC?

A

Cytotoxic drugs may perform better than expected right after CPI (a known phenomenon)

23
Q

What are DNA topoisomerases, and what’s the difference between TOP1 and TOP2?

A

Essential enzymes that stabilize DNA supercoiling and resolve when DNA gets coiled or supercoiled. Topoisomerases help by cutting the DNA strand, letting it unwind or untangle, and then rejoining it

TOP1 makes temporary single-strand cut; TOP2 makes temporary double-strand cut

24
Q

What’s the difference between a provisional- and non-provisional patent application?

A

Provisional patent: initial step that provides a filing date without starting official patent examination process. Lasts for 12 months.

Non-provisional patent: formal application that begins the examination process. Must be filed within 12 months of provisional application to benefit from provisional filing date.

25
Q

When are patents published?

A

18 months after the earliest filing date (whether provisional or non-provisional)

26
Q

What’s the typical timeline for a patent application?

A

International phase:
0: provisional patent filed (claiming priority date of initial filing)
0-1 year: file non-provisional patent in specific country (or an international application under the PCT) within this year
At 1.5 year: PCT application is published

National phase:
At 2.5 years (30/31 months from priority date): applicant must enter national phase in each country where they seek patent protection

27
Q

What were the limitations of ABBV-647?

A

~20% ORR in NSCLC and OvCa
MMAE-driven tox
Half-life ~3 days

28
Q

Indications for KIVU-107?

A

Potential indications: NSCLC, OvCa, gastric, CRC, endometrial

29
Q

Indications for KIVU-305?

A

CRC, gastric, NSCLC

30
Q

Average cost to bring a drug to market?

A

US$2.5 billion

31
Q
A

ALL (2 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions