Clinical Deep-Dive · Oncology

FDA Approves Telisotuzumab Vedotin for c‑Met High NSCLC: 35% ORR

July 15, 2026

Telisotuzumab vedotin (Emrelis) ORR

35% (95% CI: 24, 46) in LUMINOSITY [10]

Telisotuzumab vedotin (Emrelis) median DOR

7.2 months (95% CI: 4.2, 12) in LUMINOSITY [10]

Datopotamab deruxtecan PFS

Median PFS 6.9 months vs 4.9 months; HR 0.63 (95% CI: 0.52-0.76) in TROPION-Breast01 [11]

Sacituzumab govitecan PFS

Median PFS 5.6 months vs 1.7 months; HR 0.41 (95% CI: 0.32-0.52) in ASCENT [1]

Datopotamab deruxtecan confirmed ORR

36% (95% CI: 31, 42) vs 23% (95% CI: 19, 28) in TROPION-Breast01 [11]

Clinical Perspective

These regulatory decisions and trial results affect oncologists, medical oncologists, and clinicians treating patients with locally advanced or metastatic non‑squamous NSCLC with high c‑Met expression, unresectable or metastatic HR‑positive, HER2‑negative breast cancer after prior endocrine and chemotherapy, and patients with relapsed or refractory metastatic TNBC as defined in the cited trials ^[2]^[3]^[1]. The source‑confirmed data support use of telisotuzumab vedotin in c‑Met‑high non‑squamous NSCLC identified by the VENTANA MET (SP44) RxDx Assay and support datopotamab deruxtecan as an FDA‑approved option that improved PFS and ORR versus specified chemotherapies in TROPION‑Breast01, while sacituzumab govitecan showed PFS, OS, and ORR improvements versus single‑agent chemotherapy in ASCENT ^[2]^[3]^[1]. What remains unanswered is how comparative safety profiles and long‑term overall survival outcomes across these ADCs and across target antigens will inform sequencing and selection in routine practice?

Dr. Meera Pillai · Oncology

The FDA granted accelerated approval to telisotuzumab vedotin‑tllv (Emrelis) for adults with locally advanced or metastatic, non‑squamous non‑small cell lung cancer (NSCLC) with high c‑Met protein overexpression (≥50% of tumor cells with strong (3+) staining) on May 14, 2025; efficacy in the LUMINOSITY study included a confirmed overall response rate (ORR) of 35% and a median duration of response (DOR) of 7.2 months ^[2]. On January 17, 2025 the FDA approved datopotamab deruxtecan‑dlnk (Datroway) for unresectable or metastatic, HR‑positive, HER2‑negative breast cancer after prior endocrine‑based therapy and chemotherapy; the TROPION‑Breast01 trial showed a median progression‑free survival (PFS) of 6.9 months versus 4.9 months with investigator’s choice chemotherapy (HR 0.63; 95% CI 0.52-0.76) ^[3]. The ASCENT randomized phase 3 trial reported that sacituzumab govitecan prolonged PFS and overall survival versus single‑agent physician’s‑choice chemotherapy in relapsed or refractory metastatic triple‑negative breast cancer (TNBC) ^[1].

Clinical Context

Antibody‑drug conjugates (ADCs) combine a monoclonal antibody targeting a tumor antigen with a cytotoxic payload; specific ADCs in these sources target Trop‑2 or c‑Met and deliver topoisomerase inhibitors or microtubule inhibitors, respectively ^[1]^[2]^[3]. Telisotuzumab vedotin is a c‑Met‑directed antibody conjugated to a microtubule inhibitor; its approval uses a companion diagnostic, the VENTANA MET (SP44) RxDx Assay, to identify tumors with high c‑Met protein overexpression defined as ≥50% of tumor cells with strong (3+) staining ^[2]. Datopotamab deruxtecan is a Trop‑2‑directed antibody linked to a topoisomerase inhibitor and was studied in a randomized trial against named chemotherapies (eribulin, capecitabine, vinorelbine, or gemcitabine) in unresectable or metastatic HR‑positive, HER2‑negative breast cancer ^[3]. Sacituzumab govitecan is an ADC composed of an antibody targeting Trop‑2 coupled to SN‑38 via a hydrolyzable linker and was evaluated versus single‑agent physician’s‑choice chemotherapy in relapsed or refractory metastatic TNBC ^[1]. The FDA approvals for Emrelis and Datroway and the ASCENT randomized trial results together illustrate ADC development across distinct targets (c‑Met, Trop‑2), tumor types (NSCLC, HR‑positive breast cancer, TNBC), and clinical trial designs (single‑arm multi‑cohort and randomized phase 3), with companion diagnostics and randomized comparators specified where applicable ^[2]^[3]^[1].

Key Findings

The LUMINOSITY trial showed telisotuzumab vedotin achieved a confirmed overall response rate of 35% (95% CI: 24, 46) and a median duration of response of 7.2 months (95% CI: 4.2, 12) among 84 patients with EGFR wild‑type, non‑squamous NSCLC with high c‑Met protein overexpression who had received prior systemic therapy ^[2].
The TROPION‑Breast01 randomized trial showed datopotamab deruxtecan reduced the risk of progression by 37% versus investigator’s choice chemotherapy in unresectable or metastatic, HR‑positive, HER2‑negative breast cancer (HR 0.63; 95% CI: 0.52-0.76); median PFS was 6.9 months versus 4.9 months, and confirmed ORR was 36% versus 23% ^[3].
The ASCENT randomized, phase 3 trial showed sacituzumab govitecan improved median progression‑free survival to 5.6 months (95% CI, 4.3 to 6.3; 166 events) versus 1.7 months (95% CI, 1.5 to 2.6; 150 events) with single‑agent physician’s‑choice chemotherapy (hazard ratio for disease progression or death, 0.41; 95% CI, 0.32 to 0.52; P<0.001) in patients without brain metastases with relapsed or refractory metastatic TNBC ^[1].
In ASCENT median overall survival was 12.1 months (95% CI, 10.7 to 14.0) with sacituzumab govitecan and 6.7 months (95% CI, 5.8 to 7.7) with chemotherapy (hazard ratio for death, 0.48; 95% CI, 0.38 to 0.59; P<0.001), and objective response rates were 35% versus 5% ^[1].
Datopotamab deruxtecan’s randomized dataset included 732 patients randomized 1:1 (365 datopotamab, 367 chemotherapy) with stratification by prior chemotherapy lines, prior CDK4/6 inhibitor treatment, and region; median OS was 18.6 months versus 18.3 months (HR 1.01; 95% CI: 0.83, 1.22) and was not statistically significant despite PFS benefit ^[3].
Regulatory and diagnostic details: Emrelis approval was accelerated, included an FDA‑approved companion diagnostic (VENTANA MET (SP44) RxDx Assay), and used Real‑Time Oncology Review and Assessment Aid during review; datopotamab deruxtecan received full FDA approval on January 17, 2025 for its specified breast‑cancer population with full prescribing information to be posted ^[2]^[3].

Safety & Tolerability

Sacituzumab govitecan (ASCENT) — grade 3 or higher treatment‑related adverse events explicitly named: neutropenia (51% with sacituzumab govitecan and 33% with chemotherapy), leukopenia (10% and 5%), diarrhea (10% and <1%), anemia (8% and 5%), febrile neutropenia (6% and 2%). There were three deaths owing to adverse events in each group; no deaths were considered related to sacituzumab govitecan treatment ^[1].
Telisotuzumab vedotin (LUMINOSITY) — the most common adverse reactions (≥20%) were peripheral neuropathy, fatigue, decreased appetite, and peripheral edema. The most common Grade 3 or 4 laboratory abnormalities (≥2%) included decreased lymphocytes, increased glucose, increased alanine aminotransferase, increased gamma glutamyl transferase, decreased phosphorus, decreased sodium, decreased hemoglobin, and decreased calcium ^[2].
Datopotamab deruxtecan (TROPION‑Breast01) — the most common adverse reactions (≥20%), including laboratory abnormalities, were stomatitis, nausea, fatigue, decreased leukocytes, decreased calcium, alopecia, decreased lymphocytes, decreased hemoglobin, constipation, decreased neutrophils, dry eye, vomiting, increased ALT, keratitis, increased AST, and increased alkaline phosphatase ^[3].

Study Design

ASCENT (sacituzumab govitecan) was a randomized, phase 3 trial that compared sacituzumab govitecan with single‑agent chemotherapy of the physician’s choice (eribulin, vinorelbine, capecitabine, or gemcitabine) in patients with relapsed or refractory metastatic TNBC; the primary end point was progression‑free survival as determined by blinded independent central review among patients without brain metastases, and 468 patients without brain metastases were randomly assigned (235 sacituzumab govitecan, 233 chemotherapy) ^[1]. The LUMINOSITY study was a multicenter, open‑label, multi‑cohort trial that evaluated telisotuzumab vedotin in patients with EGFR wild‑type, non‑squamous NSCLC with high c‑Met protein overexpression who had received prior systemic therapy; the cohort reported here included 84 patients and the major efficacy outcome measures were confirmed ORR and duration of response determined by blinded independent central review according to RECIST 1.1 ^[2]. TROPION‑Breast01 (datopotamab deruxtecan) was a multicenter, open‑label, randomized trial in patients with unresectable or metastatic HR‑positive, HER2‑negative breast cancer who had received prior endocrine‑based therapy and one or two lines of prior chemotherapy for unresectable or metastatic disease; 732 patients were randomized 1:1 to datopotamab deruxtecan (n=365) or investigator’s choice chemotherapy (n=367) with stratification by previous lines of chemotherapy, prior CDK4/6 inhibitor, and region, and the major efficacy outcome measures were progression‑free survival (BICR per RECIST v1.1) and overall survival, with additional outcomes including confirmed ORR and DOR by BICR ^[3]. Funding and additional methodological details were reported in the respective sources where indicated (ASCENT funded by Immunomedics) and other design details not stated in the provided excerpts are not available in the provided source excerpts ^[1]^[2]^[3].

FAQ

Q1 What is telisotuzumab vedotin (Emrelis) approved for?

Telisotuzumab vedotin (Emrelis) is approved for adults with locally advanced or metastatic, non‑squamous non‑small cell lung cancer (NSCLC) with high c‑Met protein overexpression, defined as ≥50% of tumor cells with strong (3+) staining by an FDA‑approved test, for patients who have received a prior systemic therapy. The VENTANA MET (SP44) RxDx Assay is an FDA‑approved companion diagnostic to detect eligible tumors.

Q2 How does telisotuzumab vedotin work?

Telisotuzumab vedotin is a c‑Met‑directed antibody‑drug conjugate that delivers a microtubule inhibitor payload to tumor cells expressing c‑Met; the approval rationale in the LUMINOSITY study rests on a confirmed overall response rate and duration of response observed in patients with high c‑Met protein overexpression. The companion diagnostic identifies the required high c‑Met protein expression threshold for patient selection.

Q3 What is the recommended dose of telisotuzumab vedotin (Emrelis)?

The recommended dose of telisotuzumab vedotin is 1.9 mg/kg administered as an intravenous infusion every 2 weeks, with a maximum dose of 190 mg for patients weighing ≥100 kg, to be continued until disease progression or unacceptable toxicity, as stated in the FDA approval materials describing the accelerated approval and prescribing information.

Q4 What are the most common side effects of telisotuzumab vedotin?

The most common adverse reactions (≥20%) reported in the pooled safety population for telisotuzumab vedotin were peripheral neuropathy, fatigue, decreased appetite, and peripheral edema; commonly observed Grade 3 or 4 laboratory abnormalities (≥2%) included decreased lymphocytes, increased glucose, increased alanine aminotransferase, increased gamma glutamyl transferase, decreased phosphorus, decreased sodium, decreased hemoglobin, and decreased calcium.

FDA Approves Telisotuzumab Vedotin for c‑Met High NSCLC: 35% ORR

FDA Approves Telisotuzumab Vedotin for c‑Met High NSCLC: 35% ORR

Clinical Perspective

Clinical Context

Key Findings

Safety & Tolerability

Study Design

FAQ

References

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