Repotrectinib
Augtyro · ROS1/TRK TKI
2023 ROS1 inhibitor; creatinine rise via secretion block.
PSEUDO
Mild#1 · 100% phenotype match
Taletrectinib
Ibtrozi · ROS1 TKI; pseudo-AKI
ROS1 TKI · approved 2025 · 4 citations
Up to date· through 2026
Fairly sourced4/9 · 4 signals
- Not met: 4 citations
- Not met: 12+ references
- Not met: Accrued over 10+ years (span: 6y)
- Met: Beyond single case reports
- Met: High-impact journal
- Met: Landmark reference
- Met: Current through 2026
- Not met: Real-world FAERS signal
Describes how this page is sourced, not how dangerous the drug is. Thinly sourced means fewer of the sourcing signals are met — not that the agent is kidney-safe. A rule-based summary, not a formal certainty appraisal.
Next-generation ROS1 TKI with a benign, transporter-mediated creatinine bump
MildNext-generation ROS1 TKI
Locally advanced or metastatic ROS1-positive non-small cell lung cancer (NSCLC), TKI-naive or previously treated with a ROS1 TKI
§01
Signature kidney injury
Signature lesion
Drug-specific renal toxicity data for taletrectinib are limited. In the pooled TRUST-I and TRUST-II registrational safety population (352 patients at 600 mg once daily), the dominant treatment-emergent events were gastrointestinal and hepatic (elevated AST/ALT), with no defined intrinsic kidney lesion; renal-specific incidence figures are not separately reported. The expected renal signal, extrapolated from the ROS1/TRK-TKI class, is a mild, benign rise in serum creatinine from inhibition of tubular creatinine secretion rather than true GFR loss (pseudo-AKI). A precise incidence for taletrectinib-attributable creatinine elevation is not established.Source: 40179330
Onset & rechallenge
Time to injuryAcute (~1–7 days)
A class-effect transporter-mediated creatinine rise appears early after initiation and plateaus, though drug-specific timing is not separately characterized.
Distilled from: “Class-effect transporter inhibition produces a creatinine rise early after initiation that tends to plateau and is dose-dependent. Drug-specific onset timing for taletrectinib is not separately characterized.”
§02
Renal toxicities, ranked
This agent's defining kidney lesion — its #1 signature. Cited incidence is shown where a citable figure exists; otherwise the tier stands qualitatively.
The great mimic — a rise in creatinine from blocked tubular secretion (OCT2/MATE), NOT true injury. The GFR is intact; confirm with cystatin C before stopping effective therapy.
§03
Kidney injury
Mechanism of kidney injury
By class analogy to TKIs that inhibit the renal cation transporters OCT2 and MATE1/MATE2-K, the proximal-tubule pathway that secretes creatinine into urine can be blocked, raising measured serum creatinine without a fall in true GFR (pseudo-AKI). This is the same transporter-mediated mechanism demonstrated for other oncology TKIs (for example tucatinib), where iohexol- and cystatin C-based GFR remained unchanged despite a creatinine rise.
Clinical presentation
Typically an asymptomatic, mild rise in serum creatinine detected on routine labs, without oliguria, sediment abnormalities, or symptoms of true kidney injury. Cystatin C-based eGFR or a measured GFR, if obtained, would be expected to be discordantly preserved.
Management
Do not reflexively reduce or stop taletrectinib for an isolated, stable, mild creatinine rise; instead confirm it is pseudo-AKI by checking that GFR-independent markers (cystatin C eGFR or measured GFR) are preserved and that the urinalysis is bland. Reserve dose interruption for a genuine, progressive decline in filtration, sediment abnormalities, or symptomatic injury. Investigate alternative causes (volume depletion, other nephrotoxins, obstruction) when creatinine rises substantially or continues to climb.Lesion-level management framework
Risk factors
- Pre-existing chronic kidney disease (lower baseline reserve magnifies the apparent change)
- Concurrent nephrotoxins or other OCT2/MATE inhibitors
- Volume depletion (can convert a benign signal into genuine prerenal injury)
Prevention
- Establish a baseline creatinine before starting therapy
- Consider cystatin C or measured GFR to distinguish pseudo-AKI from true injury before dose changes
- Maintain euvolemia and review the concomitant medication list for additive transporter inhibition
Anticancer mechanism· how it treats cancer
Taletrectinib is an oral, CNS-active, selective next-generation ROS1 tyrosine kinase inhibitor. It binds the ATP pocket of the ROS1 kinase domain to block constitutive signaling driven by ROS1 gene fusions, and retains activity against the solvent-front G2032R resistance mutation that defeats earlier-generation agents. It has more selective ROS1 inhibition with reduced TRK-related off-target activity compared with some predecessors.
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Clinical depth
Renal dose adjustment
No dedicated renal-impairment dosing thresholds by CrCl are established in the available literature; refer to current product labeling. A benign transporter-mediated creatinine rise should not by itself trigger CrCl-based dose modification.
Dialyzability & ESKD dosing
Not characterized. As a small-molecule, highly protein-bound oral TKI, meaningful removal by hemodialysis is unlikely, but drug-specific data are lacking.
Differential diagnosis
Distinguish benign transporter-mediated pseudo-AKI from true acute kidney injury (prerenal volume depletion, ATN from concomitant nephrotoxins, or contrast injury) and from obstruction. A bland urinalysis with preserved cystatin C-based or measured GFR despite a higher creatinine points to pseudo-AKI rather than a structural lesion.
Monitoring
- Cystatin C-based eGFR or measured GFR when the etiology of a creatinine rise is unclear
- Urinalysis if true injury is suspected
- Volume status and concomitant nephrotoxins
Key trials & series
- TRUST-I and TRUST-II (pooled integrated analysis, Perol et al., J Clin Oncol 2025): among TKI-naive patients confirmed ORR 88.8 percent and median PFS 45.6 months; predominant adverse events were GI and hepatic, with neurologic events infrequent
Clinical pearls
- A mild creatinine rise on a ROS1/TRK TKI is usually a lab artifact of blocked tubular creatinine secretion, not nephron injury; chase it with cystatin C before dose-reducing.
- Unlike crizotinib, the ROS1 next-generation TKIs are not classically associated with renal cyst formation, but follow-up imaging data are immature.
Where it strikes· nephron segments & injury signatures
Nephron segments
Proximal Tubule
Bulk reabsorption + drug uptake (OCT2, OATs)
Injury signatures
Beyond the kidney — non-renal toxicities· 3 organ systems
Class-level context for the major non-renal toxicities of the ROS1 TKI class.
Ophthalmic
Keratopathy, uveitis, retinopathy
- Visual disturbance (crizotinib)
Hepatic / Liver
Transaminitis, hepatitis, VOD/SOS
- Transaminitis
Neurologic
Neuropathy, encephalopathy, ICANS, PRES
- CNS effects (lorlatinib)
§05
References
4 primary references — trials, cohorts, mechanism, and reviews. Citation metadata via PubMed / NLM.
Evidence accrual
4 references · 2020–2026 · 3 since 2024Primary (non–case-report) references per year — a proxy for how actively the agent's renal literature is accruing. Recent years are highlighted. Reflects curation depth, not a systematic bibliometric count.
- 1.LandmarkTaletrectinib in ROS1+ Non-Small Cell Lung Cancer: TRUST.Perol M, Li W, Pennell NA, et al. · J Clin Oncol · 2025 · PMID 40179330Registrational integrated efficacy/safety analysis of TRUST-I and TRUST-II; defines the pivotal safety profile (predominantly GI and hepatic) and is the source for the incidence statement that drug-specific renal data are limited.
- 2.Targeting ROS1 rearrangements in non-small cell lung cancer: Current insights and future directions.Desilets A, Repetto M, Yang SR, Drilon A · Cancer · 2025 · PMID 40171848Class review situating taletrectinib among next-generation ROS1 TKIs, including activity against G2032R and the move toward reduced TRK-mediated off-target toxicity.
- 3.LandmarkTucatinib Inhibits Renal Transporters OCT2 and MATE Without Impacting Renal Function in Healthy Subjects.Topletz-Erickson AR, Lee AJ, Mayor JG, et al. · J Clin Pharmacol · 2020 · PMID 32989831Mechanistic proof that an oncology TKI raises serum creatinine via OCT2/MATE inhibition of tubular creatinine secretion while iohexol- and cystatin C-based GFR stay unchanged, the paradigm for TKI pseudo-AKI.
- 4.Case report: successful use of repotrectinib in a ROS1 fusion-positive lung adenocarcinoma patient with severe renal insufficiency and prior tyrosine kinase inhibitor treatment failure.Liang Z, Li H · Anticancer Drugs · 2026 · PMID 41903327Documents real renal events (rising creatinine, renal cysts, atrophy) during sequential ROS1 TKI therapy, underscoring that creatinine changes on this class warrant nephrology assessment to separate benign from true injury.
Guidelines & consensus· 13
Each recommendation below is this atlas's faithful summary of the source, not a quotation from it — follow the PubMed link for the wording the society published. Summaries may be superseded; consult the current full text and individualize to the patient.
General onco-nephrology references
ADQIThe nephrotoxic effects of anti-cancer therapies: consensus report of the 34th Acute Disease Quality Initiative workgroupNat Rev Nephrol 2026 · PMID 41361704Provides expert-based statements (modified Delphi) on preventing and managing cisplatin/platinum-associated AKI, including isotonic IV hydration, attention to volume status and concomitant nephrotoxins, and incorporates evidence that IV magnesium supplementation may reduce cisplatin-associated AKI; emphasizes risk stratification and standardized AKI definitions.SIRMSIRM-SIN-AIOM: appropriateness criteria for evaluation and prevention of renal damage in the patient undergoing contrast medium examinations-consensus statements from Italian College of Radiology (SIRM), Italian College of Nephrology (SIN) and Italian Association of Medical Oncology (AIOM)Radiol Med 2022 · PMID 35303246Recommends eGFR-based renal risk assessment and pre/post-contrast isotonic saline or sodium bicarbonate hydration; advises maintaining a 5-7 day interval between iodinated contrast administration and cisplatin in cancer patients to reduce additive nephrotoxicity.KDIGOKDIGO Controversies Conference on onco-nephrology: understanding kidney impairment and solid-organ malignancies, and managing kidney cancerKidney Int 2020 · PMID 33126977Identifies platinum compounds (especially cisplatin) as leading cytotoxic causes of acute tubular injury, AKI, and electrolyte/magnesium wasting; calls for interdisciplinary onco-nephrology care, accurate GFR estimation, and individualized drug dosing in patients with reduced kidney function.KDIGOKDIGO Controversies Conference on onco-nephrology: kidney disease in hematological malignancies and the burden of cancer after kidney transplantationKidney Int 2020 · PMID 33276867Addresses chemotherapy-associated AKI/CKD in hematologic cancer, GFR estimation and chemotherapy dosing in patients with reduced kidney function, and management priorities and research gaps for onco-nephrology care.ADDIKDIntegrating International Consensus Guidelines for Anticancer Drug Dosing in Kidney Dysfunction (ADDIKD) into everyday practiceEClinicalMedicine 2025 · PMID 40290844Provides GRADE-based, drug-specific dose-adjustment recommendations for anticancer agents in kidney dysfunction (illustrated for methotrexate, cisplatin, carboplatin and nivolumab); the recommendations build on Part 1's standardised CKD-EPI eGFR assessment rather than Cockcroft-Gault creatinine clearance.ADDIKDAligning kidney function assessment in patients with cancer to global practices in internal medicineEClinicalMedicine 2025 · PMID 40290845Three consensus recommendations: assess kidney function by GFR (measured GFR or CKD-EPI eGFR), classify it using KDIGO categories, and use this uniform approach to dose anticancer drugs — moving cancer medicine away from Cockcroft-Gault estimated creatinine clearance.ADDIKDA methodology for determining dosing recommendations for anticancer drugs in patients with reduced kidney functionEClinicalMedicine 2025 · PMID 40290846Establishes that, where RCT evidence is lacking, anticancer drug dosing recommendations in kidney dysfunction should be derived by critically appraising observational literature via GRADE combined with structured international multidisciplinary consensus voting.KDIGODiagnosis, evaluation, and management of acute kidney injury: a KDIGO summary (Part 1)Crit Care 2013 · PMID 23394211Defines/stages AKI by serum creatinine and urine output; emphasizes avoiding nephrotoxins, maintaining euvolemia/perfusion, dose-adjusting drugs to kidney function, and monitoring high-risk patients — the framework applied to nephrotoxic anti-cancer agents.KDIGOExecutive summary of the KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease: known knowns and known unknownsKidney Int 2024 · PMID 38519239Evaluate and risk-stratify CKD, manage to delay progression and its complications, and practise explicit medication management and drug stewardship — the framework the atlas's G1–G5 eGFR banding and every renal dose-adjustment recommendation sit inside. Because the guideline excludes dialysis and transplant recipients by its own statement of scope, its recommendations do not carry to those settings, where this atlas's dialyzability and post-transplant guidance rests on other sources.KDIGOExecutive summary of the KDIGO 2021 Guideline for the Management of Glomerular DiseasesKidney Int 2021 · PMID 34556300Provides the staging/treatment framework for drug-associated glomerular lesions (e.g., bisphosphonate- and interferon-related collapsing FSGS, VEGF-inhibitor podocytopathy/proteinuria), including immunosuppression and supportive RAAS-blockade strategies.KDIGOExecutive summary of the KDIGO 2024 Clinical Practice Guideline for the Management of ANCA-Associated VasculitisKidney Int 2024 · PMID 38388147Updates immunosuppressive induction (rituximab/cyclophosphamide), incorporates avacopan and lower-dose or glucocorticoid-sparing regimens — the management framework for drug- and checkpoint-inhibitor-associated ANCA/pauci-immune glomerulonephritis.KDIGOExecutive summary of the KDIGO 2024 Clinical Practice Guideline for the Management of Lupus NephritisKidney Int 2024 · PMID 38182299Updates first-line lupus nephritis therapy to combination immunosuppression with the addition of belimumab or a calcineurin inhibitor (voclosporin) — informs management of immune-complex/lupus-like glomerulonephritis encountered with immunotherapy.KDIGOExecutive summary of the KDIGO 2025 Clinical Practice Guideline for the Management of Immunoglobulin A Nephropathy (IgAN) and Immunoglobulin A Vasculitis (IgAV)Kidney Int 2025 · PMID 40975525Encourages liberal kidney biopsy and stricter proteinuria control (<0.5 g/d, ideally <0.3 g/d) with RAAS blockers, SGLT2 inhibitors, and targeted-release budesonide — the framework for IgA-dominant glomerular lesions, including those triggered by immune-modulating cancer therapy.
Where Taletrectinib sits in nephrotoxicity space — each dot is an anti-cancer agent, positioned so neighbors share a kidney-injury phenotype. Its 6 closest are filled and lead to a numbered marker, matching the numbered cards below.
Phenotype-similar agents· the numbered markers on the map above
Profile
Entrectinib
Rozlytrek · TRK/ROS1 TKI
Creatinine rise via reduced tubular secretion.
PSEUDO
Mild#2 · 100% phenotype match
Larotrectinib
Vitrakvi · TRK inhibitor
Mild creatinine rise; generally well tolerated.
PSEUDO
Mild#3 · 99% phenotype match
Tucatinib
Tukysa · HER2 TKI
Benign creatinine rise via tubular secretion inhibition.
PSEUDO
Mild#4 · 89% phenotype match
Rucaparib
Rubraca · PARP inhibitor
Transporter-mediated creatinine rise.
PSEUDO
Mild#5 · 74% phenotype match
Talazoparib
Talzenna · PARP inhibitor
Renally cleared; creatinine rise.
PSEUDO
Mild#6 · 74% phenotype match
Nearest agents by kidney-injury phenotype (shared injuries, nephron target, severity, class) — a similarity approximation, not a claim of shared drug identity or mechanism.
Kidney risk across ALK / ROS1 / MET / TRK inhibitors
Same-class agents ordered by their documented kidney-injury profile — atlas severity, an acute-kidney-injury FAERS signal, and how many injury types each is documented to cause. Agents nearer the top carry the lighter documented renal profile.
- 1LarotrectinibPSEUDO — Pseudo-AKIMild
- 2RepotrectinibPSEUDO — Pseudo-AKIMild
- 3Taletrectinib· this agentPSEUDO — Pseudo-AKIMild
- 4ZidesamtinibPRE — Prerenal / Hemodynamic AKIMild
- 5AlectinibPSEUDO — Pseudo-AKIMild
- 6CapmatinibPSEUDO — Pseudo-AKIMild
- 7CeritinibPRE — Prerenal / Hemodynamic AKIMild
- 8TepotinibPSEUDO — Pseudo-AKIMild
- 9BrigatinibPSEUDO — Pseudo-AKIMild
- 10CrizotinibRCYST — Renal CystsMild
- 11EnsartinibPSEUDO — Pseudo-AKIMild
- 12LorlatinibPSEUDO — Pseudo-AKIMild
- 13EntrectinibPSEUDO — Pseudo-AKIFAERS AKIMild
A comparison of documented kidney-injury data within one drug class — not a substitution recommendation. Efficacy, indication, and non-renal toxicity differ between these agents and are out of scope here. Educational only, not medical advice.