DATOPOTAMAB DERUXTECAN-DLNK INJ,LYPHL

Clinical Criteria Summary

Absolute neutrophil count (ANC) <1,500/mm3 (unless Duffy null phenotype) or platelets <100,000/mm3
Severe renal impairment: CrCl <30 mL/minute
Severe hepatic impairment: total bilirubin >1.5 times ULN and any AST/ALT; or total bilirubin >3 times ULN and any AST/ALT if liver metastases
Symptomatic or unstable brain metastases
History of interstitial lung disease (ILD)/pneumonitis requiring steroids, or active ILD/pneumonitis
Uncontrolled or significant cardiac disease: Baseline Left Ventricular Ejection Fraction (LVEF) < 50% via MUGA or echocardiography; uncontrolled hypertension or arrhythmia; myocardial infarction or unstable angina within prior 6 months; symptomatic Congestive Heart Failure (New York Heart Assoc. Class 2 - 4); mean corrected QT interval > 470 msec
Clinically significant corneal disease
Prior treatment with topoisomerase I inhibitor (e.g. fam-trastuzumab deruxtecan or irinotecan) or Trop-2-directed therapy (e.g. sacituzumab govitecan)
Known pregnancy
Lactating

Unresectable or metastatic, hormone receptor (HR)-positive, human epidermal growth factor 2 (HER2)-negative (IHC 0, IHC 1+, or IHC 2+/ISH-) breast cancer after prior endocrine-based therapy and chemotherapy for unresectable or metastatic disease
Locally advanced or metastatic epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) after prior EGFR-directed therapy and platinum-based chemotherapy

In-person baseline ophthalmic exam (visual acuity testing, slit lamp examination, intraocular pressure, and fundoscopy) prior to treatment initiation
Able to administer preservative-free lubricant eye drops at least four times daily and as needed throughout the duration of treatment with datopotamab deruxtecan
Able to avoid wearing contact lenses, unless otherwise directed by ophthalmologist
Able to administer steroid-containing mouthwash (dexamethasone oral solution 0.1 mg/mL) four times daily and as needed throughout the duration of treatment with datopotamab deruxtecan
Care is provided by a VA/VA Community Care oncology provider
Eastern Cooperative Oncology Group (ECOG) performance status 0-1
Goals of care and role of Palliative Care consult have been discussed and documented

Females who can become pregnant and males with partners who can become pregnant: Counseling provided on risks vs benefits and use of effective contraception during therapy and for 7 months after stopping treatment for women and 4 months after for men.

Unresectable or metastatic, hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative (IHC 0, IHC 1+, or IHC 2+/ISH-) breast cancer after prior endocrine-based therapy and chemotherapy for unresectable or metastatic disease
Locally advanced or metastatic epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) after prior EGFR-directed therapy and platinum-based chemotherapy
Currently under accelerated approval based on objective response rate (ORR) and duration of response from the TROPION-Lung05 and TROPION-Lung01 trials

≥18 years of age
ECOG performance status 0-1
Breast cancer: Inoperable or metastatic HR+/HER2- breast cancer; 1-2 prior lines of chemotherapy in the inoperable/metastatic setting; progression on or unsuitable for endocrine therapy
NSCLC: Advanced or metastatic NSCLC with actionable genomic alterations (EGFR, ALK, ROS1, NTRK, BRAF, MET exon 14 skipping, RET); 1-2 prior lines of cytotoxic therapies (at least 1 platinum-containing regimen) and 1-2 prior lines of targeted therapies for actionable mutations

History of interstitial lung disease (ILD)/pneumonitis requiring steroids or active ILD/pneumonitis
Uncontrolled or significant cardiac disease
Clinically significant corneal disease
Prior treatment with topoisomerase I inhibitors, Trop-2-directed therapy, or same investigator choice chemotherapy (ICC) [breast cancer] / prior treatment with docetaxel [NSCLC Lung01]
Untreated or symptomatic CNS metastases
KRAS mutations without other aforementioned alterations [NSCLC]
Embryo-fetal toxicity: Can cause fetal harm in a pregnant woman; effective contraception required

Pre-medications recommended to be given 30-60 minutes prior to each infusion: Diphenhydramine 25-50mg PO/IV or equivalent, Acetaminophen 650-1,000mg PO/IV or equivalent, and a 5-HT3 serotonin antagonist or other appropriate antiemetic PO/IV
Patient should hold ice chips in mouth throughout the duration of each infusion
High-emetic risk requiring scheduled and as-needed antiemetics
Preservative-free lubricant eye drops for both eyes at least four times daily
Dexamethasone 0.1mg/mL oral solution (or equivalent) to swish/spit 10 mL four times daily

Ophthalmic exam required prior to treatment initiation, annually while on treatment, and at the end of treatment
Monitor for interstitial lung disease (ILD)/pneumonitis, ocular adverse reactions (dry eye, keratitis, increased lacrimation), and stomatitis
Intensive supportive care is necessary; significant toxicity profile must be considered in the context of the Veteran population

Breast cancer: Second line with visceral crisis or endocrine refractory disease (category 2A); first line for triple-negative disease with PD-L1 CPS <10 and no germline BRCA mutations (category 2A, preferred)
Lack of mature overall survival (OS) data favors use of previously approved antibody-drug conjugates (fam-trastuzumab deruxtecan and sacituzumab govitecan); no data exists for use after prior ADCs
NSCLC: Subsequent therapy for EGFR mutations/alterations (category 2A); may serve as an effective option given limited options following systemic chemotherapy and EGFR tyrosine kinase inhibitors, filling the role for acquired resistance or failed prior lines of therapy
Trop-2 is not currently tested through the VHA National Precision Oncology Program (NPOP); expression was not associated with differences in response in TROPION-Lung05 and was not reported in Lung01 or Breast01