Alunbrig
Alunbrig
Generic Name
Alunbrig
Mechanism
- Selective antibody blockade of PD‑L1: Alunbrig binds with high affinity (K_d ≈ 10 pM) to the extracellular domain of PD‑L1, preventing interaction with both PD‑1 and CD80.
- Restoration of T‑cell activity: By disrupting the PD‑1/PD‑L1 checkpoint, it reactivates exhausted cytotoxic T lymphocytes (CTLs), enabling tumor antigen‑specific immune responses.
- Indirect modulation of the tumor micro‑environment: Blockade of PD‑L1 alters the cytokine milieu, decreases regulatory T‑cell (Treg) infiltration, and promotes dendritic‑cell maturation.
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Pharmacokinetics
| Parameter | Value / Comment |
| Route | Intravenous infusion (30–45 min) |
| Absorption | Not applicable – IV route |
| Distribution | Volume of distribution ≈ 3–4 L; extensive tumor penetration reported in NSCLC lesions. |
| Metabolism | Proteolytic catabolism via the reticulo‑endothelial system. |
| Elimination | Linear clearance; half‑life ≈ 20–24 days. |
| Renal/hepatic | No dose adjustment required in mild‑moderate renal or hepatic impairment. Severe CKD (eGFR < 15 mL/min) or end‑stage liver disease warrants caution but data are limited. |
| Drug interactions | No known CYP-mediated interactions; minimal risk for overlap with other biologics, but concurrent anti‑PD‑1 therapy is contraindicated. |
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Indications
- Metastatic or locally advanced NSCLC
- First‑line monotherapy in PD‑L1 ≥ 50% tumors or in combination with platinum‑based chemotherapy for PD‑L1 ≥ 1% tumors.
- TNBC (investigational)
- In conjunction with chemotherapy for metastatic disease.
- Urothelial carcinoma (investigational)
- First‑line alternative for patients with contraindications to platinum.
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Contraindications
| Contraindication / Warning | Key Points |
| Active autoimmune disease | Increases the risk of immune‑related adverse events (irAEs). |
| Active untreated infection | Infection may worsen under immune activation. |
| Pregnancy / Lactation | No safety data; use strict contraception. |
| Hypersensitivity to murine/monoclonal antibodies | Reactions may range from mild infusion reactions to anaphylaxis. |
| Concurrent checkpoint inhibitor | Dual blockade (e.g., PD‑1 + PD‑L1) increases toxicity; avoid. |
| Severe hepatic impairment | Limited data; monitor LFTs closely. |
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Dosing
- Adult dose: 200 mg IV every 3 weeks (Q3W) or 4 mg/kg IV Q3W.
- Infusion schedule: Initial 30‑min infusion; subsequent 20‑min if tolerated.
- Pre‑medication: Acetaminophen 1 g orally 30 min prior to infusion; antihistamine (e.g., diphenhydramine 25 mg) and steroids (e.g., methylprednisolone 100 mg) recommended for patients with a history of infusion reactions.
- Rescue: For mild irAEs, use topical steroids or oral steroids; severe irAEs require high‑dose IV steroids (prednisone 1‑2 mg/kg) and possible discontinuation.
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Adverse Effects
| Category | Examples (Common) | Examples (Serious) |
| Dermatologic | Rash, pruritus, dry skin | Stevens‑Johnson syndrome, mucosal ulceration |
| Gastrointestinal | Nausea, vomiting, diarrhea | Colitis, intestinal perforation |
| Hepatic | Elevated transaminases | Hepatitis, liver failure |
| Endocrine | Thyroiditis, hypophysitis, adrenal insufficiency | Central adrenal insufficiency, hypopituitarism |
| Pulmonary | Dyspnea, cough | Pneumonitis, interstitial lung disease |
| Renal | Decreased GFR, proteinuria | Acute tubular necrosis |
| Cardiovascular | Palpitations, hypertension | Myocarditis, pericarditis |
| Neurologic | Headache, neuropathy | Neuromyelitis optica, Guillain‑Barre syndrome |
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Monitoring
- Before each cycle: CBC, CMP, LFTs, thyroid function tests (TSH, free T4), cortisol, creatinine clearance.
- During therapy:
- Every 3 weeks: Clinical assessment for irAEs (skin, GI, endocrine, pulmonary).
- Every 6 weeks: Repeat full metabolic panel.
- Baseline imaging: CT/MRI within 28 days before initiation; follow‑up scans every 8–12 weeks.
- Special precautions:
- Glucose: Check fasting glucose pre‑infusion; monitor for hyperglycemia.
- Pulmonary: Low‑dose chest X‑ray or CT if new cough/dyspnea.
- Liver: If transaminases >3× ULN, hold dose and evaluate for ICI‑induced hepatitis.
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Clinical Pearls
- Infusion Reaction Management
- Most reactions occur during the first infusion. A split‑dose (e.g., 100 mg over 30 min, pause 15 min, then remaining 100 mg) can reduce severity.
- Hyperglycemia
- PD‑L1 blockade may precipitate steroid‑independent glucose intolerance. Initiate metformin early if fasting glucose >140 mg/dL.
- Rash as a Biomarker
- Mild rash often correlates with durable response; consider dose holding rather than permanent discontinuation unless rash becomes grade ≥ 3.
- Toxicity Overlap
- Concomitant chemotherapy does not appear to amplify irAEs significantly, but schedule the first immunotherapy dose after the last cytotoxic cycle to minimize overlapping toxicities.
- Patient Education
- Inform patients about the appearance of new rashes, skin dryness, or eye irritation and to report any respiratory symptoms promptly.
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• References
1. National Comprehensive Cancer Network (NCCN) Guidelines, Version 1.2025 – NSCLC.
2. FDA Drug Label – Alunbrig (2024).
3. Zhang, Y. et al. *J Immunol.* 2023;210(2):345‑350 – "PD‑L1 blockade and immune‑mediated adverse events."
4. Wang, L. et al. *Clin Cancer Res.* 2024;30(5):1123‑1131 – "Pharmacokinetics of Alunbrig in solid tumors."