15 ADC Drugs: Dosage and Usage Summary

15 ADC Drugs: Dosage and Usage Summary
Currently, there are 15 ADC drugs approved globally, among which 6 ADC drugs have been approved in China, namely Trastuzumab emtansine, Brentuximab vedotin, Trastuzumab deruxtecan, Vidofludimus, Gemtuzumab ozogamicin, and Sacituzumab govitecan.
This article provides a brief summary based on the currently approved ADC drugs worldwide, the types of tumors they are suitable for, and how to use them.
1. Trastuzumab emtansine (Target: HER-2)
· Indications
Adjuvant treatment for breast cancer: Monotherapy is suitable for HER2-positive early breast cancer patients with residual invasive lesions after receiving taxane-based neoadjuvant therapy combined with trastuzumab.
Treatment of metastatic breast cancer: Monotherapy is suitable for HER2-positive, unresectable locally advanced or metastatic breast cancer patients who have received taxane and trastuzumab therapy. Patients should meet one of the following conditions: previously treated for locally advanced or metastatic breast cancer, or experiencing disease recurrence within 6 months during or after adjuvant therapy.
· Proper Use
The recommended dosage is 3.6 mg/kg, once every 3 weeks (21 days per cycle), administered intravenously.
Trastuzumab emtansine (T-DM1) and trastuzumab are different drugs and should not be substituted in clinical applications.
Dilute in 250 ml of 0.45% or 0.9% sodium chloride; do not use 5% dextrose solution for dilution, as it can cause protein aggregation, and do not mix or dilute with other drugs. If using 0.9% sodium chloride for infusion, a 0.2/0.22μm inline polyethersulfone filter is required. Once prepared for infusion, it should be administered immediately. If not used immediately, the infusion solution can be stored in a refrigerator at 2-8°C for up to 24 hours. Do not freeze or shake the infusion bag during storage.
2. Brentuximab vedotin (Target: CD30)
· Indications
For patients with relapsed or refractory systemic anaplastic large cell lymphoma. For patients with relapsed or refractory classical Hodgkin lymphoma. For patients with primary cutaneous anaplastic large cell lymphoma or mycosis fungoides who have previously received systemic treatment.
· Proper Use
The recommended dosage is 1.8 mg/kg, administered intravenously over more than 30 minutes, once every 3 weeks. It should not be administered as a rapid IV push or bolus. It can only be administered through a dedicated IV access and should not be mixed with other drugs.
Withdraw an appropriate volume of reconstituted brentuximab vedotin into an infusion bag containing 9 mg/mL (0.9%) sodium chloride solution to achieve a final concentration of 0.4-1.2 mg/mL. The recommended dilution volume is 150 mL. 5% dextrose injection or lactated Ringer’s solution can also be used for diluting reconstituted brentuximab vedotin.
Avoid use in patients with severe renal impairment (creatinine clearance <30 ml/min).
3. Trastuzumab deruxtecan (Target: HER-2)
· Indications
For patients with HER2-overexpressing locally advanced or metastatic gastric cancer (including gastroesophageal junction adenocarcinoma) who have received at least 2 systemic chemotherapies. HER2 overexpression is defined as immunohistochemistry results of 2+ or 3+, regardless of FiSH/CiSH amplification.
· Proper Use
The recommended dosage is 2.5 mg/kg, administered intravenously every 2 weeks, for a duration of 30-90 minutes (usually recommended around 60 minutes).
No dose adjustment is needed for patients with mild liver impairment; the impact of moderate to severe liver impairment on the pharmacokinetics of this drug has not been studied; no dose adjustment is needed for patients with mild to moderate renal impairment, and there is no research data on patients with severe renal impairment.
4. Sacituzumab govitecan (Target: Trop-2)
· Indications
This drug is indicated for adult patients with unresectable locally advanced or metastatic triple-negative breast cancer who have received at least two systemic treatments (one of which is for metastatic disease).
On February 3, 2023, the FDA approved sacituzumab govitecan (SG) for adult patients with hormone receptor (HR)-positive, HER2-negative (IHC 0, 1+, or 2+/ISH -) unresectable locally advanced or metastatic breast cancer who have previously received endocrine therapy and ≥2 lines of systemic treatment (targeting metastatic disease).
· Proper Use
The recommended dosage is 10 mg/kg, administered intravenously on Day 1 and Day 8, with a treatment cycle of 21 days. The dosage should not exceed 10 mg/kg, and it can only be administered via intravenous infusion, not as a rapid IV push; the first infusion should last at least 3 hours.
The most common adverse reactions are neutropenia and diarrhea.
5. Inotuzumab ozogamicin (Target: CD22)
· Indications
Indicated for adult patients with relapsed or refractory precursor B-cell acute lymphoblastic leukemia (ALL).
· Proper Use
The recommended total dosage is 1.8 mg/m2, divided into 3 doses on Day 1 (0.8 mg/m2), Day 8 (0.5 mg/m2), and Day 15 (0.5 mg/m2). The duration of the first cycle is 3 weeks, and subsequent cycles last 4 weeks.
No adjustment of starting dose is needed for patients with mild, moderate, or severe renal impairment (creatinine clearance of 60-89 mL/min, 30-59 mL/min, or 15-29 mL/min, respectively).
6. Trastuzumab deruxtecan (Target: HER-2)
· Indications
Indicated for adult patients with unresectable or metastatic HER2-positive breast cancer who have previously received more than 2 HER2-targeted therapies; adult patients with unresectable or metastatic HER-2 low-expressing (IHC 1+ or IHC 2+/ISH-) breast cancer who relapsed during or within six months after completing adjuvant chemotherapy; and patients with locally advanced or metastatic HER-2 positive gastric or gastroesophageal junction adenocarcinoma who have previously received trastuzumab-based regimens.
On February 24, 2023, the NMPA issued an approval for the first HER2 ADC “Trastuzumab deruxtecan” by Daiichi Sankyo/AstraZeneca in China, for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have previously received one or more anti-HER2 drug treatments.
· Proper Use
The recommended dosage is 5.4 mg/kg, administered intravenously every 3 weeks until disease progression or unacceptable toxicity. Do not administer as a rapid IV push or rapid injection; the first infusion should last no less than 90 minutes, and if well tolerated, subsequent infusions should last no less than 30 minutes.
7. Gemtuzumab ozogamicin (Target: CD33)
· Indications
Indicated for acute myeloid leukemia (AML).
· Proper Use
The recommended dosage is 3 mg/m2, for intravenous infusion only, not for rapid intravenous injection; it is best completed via a large vein over 2 hours.
8. Moxetumomab pasudotox (Target: CD22)
· Indications
Indicated for the treatment of adult patients with relapsed or refractory hairy cell leukemia (HCL).
· Proper Use
The recommended dosage is 0.04 mg/kg, administered intravenously for more than 30 minutes on Days 1, 3, and 5 of a 28-day cycle, until six cycles of treatment are completed or disease progression occurs, or unacceptable toxicity is observed. It is not recommended for patients with severe renal impairment.
9. Polatuzumab vedotin (Target: CD79b)
· Indications
Indicated for adult patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) who have received at least two prior treatments.
· Proper Use
The recommended dosage is 1.8 mg/kg administered intravenously every 21 days, in combination with bendamustine and rituximab for 6 cycles. Antihistamines and antipyretics should be administered at least 30 minutes before Polatuzumab vedotin.
10. Enfortumab vedotin (Target: Nectin-4)
· Indications
Indicated for adult patients with locally advanced or metastatic urothelial carcinoma who have previously received PD-1 or PD-L1 inhibitors, and for patients treated with platinum-based chemotherapy in neoadjuvant/adjuvant, locally advanced, or metastatic settings.
· Proper Use
The recommended dosage is 1.25 mg/kg (maximum dosage 125 mg), administered intravenously over 30 minutes on Days 1, 8, and 15 of a 28-day cycle, until disease progression or unacceptable toxicity occurs.
Avoid use in patients with moderate to severe liver impairment.
11. Belantamab mafodotin (Target: B cell maturation antigen)
· Indications
Indicated for adult patients with relapsed or refractory multiple myeloma who have previously received at least 4 therapies (including anti-CD38 monoclonal antibodies, proteasome inhibitors, and immunomodulators).
· Proper Use
The recommended dosage is 2.5 mg/kg, administered intravenously every 3 weeks for approximately 30 minutes, until disease progression or unacceptable toxicity occurs; based on adverse reactions, the recommended dosage is 1.9 mg/kg intravenously every 3 weeks; discontinue if unable to tolerate the 1.9 mg/kg dosage.
12. Cetuximab saratolacan (Target: EGFR)
· Indications
Indicated for the treatment of unresectable locally advanced or recurrent head and neck cancer.
13. Loncastuximab tesirine (Target: CD19)
· Indications
Indicated for adult patients with relapsed or refractory (R/R) large B-cell lymphoma (LBCL), including diffuse large B-cell lymphoma (DLBCL), DLBCL originating from low-grade lymphoma, and high-grade cell lymphoma.
14. Tisotumab vedotin-tftv
· Indications
Indicated for the treatment of adult patients with relapsed or metastatic cervical cancer that progressed during or after chemotherapy.
· Proper Use
The recommended dosage is 2 mg/kg (up to 200 mg for patients ≥100 kg), administered intravenously every 3 weeks, over 30 minutes, until disease progression or unacceptable toxicity occurs.
15. Mirvetuximab soravtansine (Target: Folate receptor α)
· Indications
Indicated for adult patients with folate receptor α (FRα) positive platinum-resistant ovarian epithelial cancer, fallopian tube cancer, or primary peritoneal cancer who have previously received 1-3 lines of systemic treatment.

Conclusion

Currently, there are 15 ADC drugs approved globally, with 5 approved in China. It is believed that with the continuous development and progress of drugs, more ADC drugs will be approved in China, bringing treatment hope to more cancer patients.

Author: Jin Haobing;Editor: Cai Yuhan

Cover Image: Zcool Hailuo PLUS

Submission: [email protected]

15 ADC Drugs: Dosage and Usage Summary

References

1. Fu Z, Li S, Han S, et al. Antibody drug conjugate: the “biological missile” for targeted cancer therapy. [J]. Signal Transduct Target Ther, 2022.

2. Expert consensus on clinical application of antibody-drug conjugates for malignant tumors (2020 edition)

3. Drug instructions

4. Guidelines for clinical application of new anti-tumor drugs (2022 edition)

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