OVERVIEW

Telisotuzumab adizutecan (ABBV-400, Temab-A) is an investigational drug under clinical development. Safety and efficacy have not been established.

Temab-A—an antibody-drug conjugate (ADC)—designed to target c-Met by deploying a payload of topoisomerase inhibitor. It is being investigated in colorectal cancer (CRC), non-small cell lung cancer (NSCLC), and gastroesophageal adenocarcinoma (GEA), and MET-amplified solid tumors.

PROPOSED MECHANISM OF ACTION

The protein, mesenchymal-epithelial transition factor (c-Met), which is also known as MET protein, AUTS9, RCCP2, DFNB97, and hepatocyte growth factor receptor (HGFR), is essential for the survival and function of normal cells.¹

In numerous cancers, the MET gene, which encodes the protein c-Met, is either amplified or mutated to constantly activate its downstream signaling pathways to sustain rapid proliferation and survival of cancer cells. In NSCLC, both c-Met and HGF are over-expressed relative to the adjacent normal lung tissues.¹

The mechanism of action of c-Met ADCs involves three steps: binding to c-Met protein on the cell surface, internalizing of ADC/c-Met receptor complexes, and releasing the cytotoxic payload within the cytosol to damage cells.

Temab-A delivers topoisomerase inhibitors to c-Met protein expressing cells, which inhibits DNA replication; this helps stop cell proliferation and ultimately lead to cell death.

Clinical relevance of proposed mechanism and structure activity relationships is under investigation

DEVELOPMENT

Temab-A is being investigated to treat CRC, NSCLC, GEA, and MET-amplified solid tumors.

CLINICAL TRIALS

View select clinical trials with Temab-A now. To view a full list of clinical trials in which Temab-A is being investigated, please visit  ClinicalTrials.gov.

1. Park KC, Richardson DR. The c-MET oncoprotein: function, mechanisms of degradation and its targeting by novel anti-cancer agents. Biochim Biophys Acta Gen Subjs. 2020;1864(10):129650

OVERVIEW

ABBV-514 is an investigational drug under clinical development. Safety and efficacy have not been established.

ABBV-514 is an anti-chemokine C-C motif receptor 8 (CCR8) antibody that is being investigated for the treatment advanced solid tumors both as a single agent and in combination with a PD-1 inhibitor.

PROPOSED MECHANISM OF ACTION

CCR8 is a chemokine receptor that has been previously associated with chemotaxis and cell/cell interactions in the context of T-helper type 2 cell responses and T-cell trafficking to the skin^1-2. Within tumors, regulatory T-cells (Tregs) are a key immunosuppressive cell population known to prevent antitumor immune responses; high intratumoral Treg levels have been associated with negative outcomes in several cancers.^3-5 CCR8 is overexpressed in Tregs found in the tumor microenvironment(TME) and is upregulated in tumor tissues, including HNSCC, NSCLC, and colorectal cancer (CRC).^6-8 CCR8 is preferentially expressed on tumor-infiltrating Tregs and correlates with poor prognosis in both NSCLC and CRC patients.⁷

DEVELOPMENT

ABBV-514 is being investigated in a Phase 1 trial for advanced solid tumors.

CLINICAL TRIALS

View select clinical trials with ABBV-514 now. To view a full list of clinical trials in which ABBV-514 is being investigated, please visit ClinicalTrials.gov.

References

1. Chensue SW, Lukacs NW, Yang TY, et al. Aberrant in vivo T helper type 2 cell response and impaired eosinophil recruitment in CC chemokine receptor 8 knockout mice. J Exp Med. 2001;193:573-584.
2. Schaerli P, Ebert L, Willimann K, et al. A skin-selective homing mechanism for human immune surveillance T cells. J Exp Med. 2004;199:1265-1275.
3. Shang B, Liu Y, Jiang SJ, et al. Prognostic value of tumor-infiltrating FoxP3+ regulatory T cells in cancers: a systematic review and meta-analysis. Sci Rep. 2015;5:15179.
4. Fridman WH, Zitvogel L, Sautes-Fridman C, et al. The immune contexture in cancer prognosis and treatment. Nat Rev Clin Oncol. 2017;14(12):717-34.
5. Bruni D, Angell HK, Galon J. The immune contexture and Immunoscore in cancer prognosis and therapeutic efficacy. Nat Rev Cancer. 2020;20(11):662-80.
6. Meng L, et al. CCR4, CCR8, and P2RY14 as prognostic factors in head and neck squamous cell carcinoma are involved in the remodeling of the tumor microenvironment. Front Oncol. 2021;11:618187.
7. De Simone M, et al. Transcriptional landscape of human tissue lymphocytes unveils uniqueness of tumor-infiltrating t regulatory cells. Immunity. 2016;45:1135-1147.
8. Plitas G, Konopacki C, Wu K, et al. Regulatory T cells exhibit distinct features in human breast cancer. Immunity. 2016;45(5):1122-34.

OVERVIEW

ABBV-706  is an investigational drug under clinical development. Safety and efficacy have not been established.

ABBV-706 is a SEZ6-targeted antibody-drug conjugate (ADC) being investigated in advanced solid tumors.

PROPOSED MECHANISM OF ACTION

Seizure-related homolog 6 (SEZ6) is a transmembrane protein found on the cell surface of select neuronal lineage cells.^1,2

SEZ6 is highly expressed on neuroendocrine neoplasms, including small-cell lung cancer (SCLC), high-grade neuroendocrine tumors (NETs)/neuroendocrine carcinomas (NECs), and central nervous system (CNS) tumors, and has limited expression in normal tissues outside of the blood-brain barrier.³ SEZ6 was chosen as a target for the development of novel ADCs carrying payloads designed to kill neuroendocrine tumor cells.⁴ ABBV-706 targets cells expressing SEZ6, is rapidly internalized, and delivers a cell killing topoisomerase 1 inhibitor (Top1i) payload.⁵

DEVELOPMENT

ABBV-706 is being investigated in a Phase 1 trial for the treatment of advanced solid tumors, including small cell lung cancer (SCLC), central nervous system (CNS) tumors, and neuroendocrine tumors (NETs)/neuroendocrine carcinomas (NECs). 

CLINICAL TRIALS

View select clinical trials with ABBV-706 now. To view a full list of clinical trials in which ABBV-706 is being investigated, please visit ClinicalTrials.gov.

1. Shimizu-Nishikawa K, et al. Cloning and characterization of seizure-related gene, SEZ-6. Biochem Biophys Res Commun. 1995;216(1):382-9.
2. Gunnersen JM, et al. Sez-6 proteins affect dendritic arborization patterns and excitability of cortical pyramidal neurons. Neuron. 2007;56(4):621-39.
3. Kudoh S, et al. Significance of achaete-scute complex homologue 1 (ASCL1) in pulmonary neuroendocrine carcinomas; RNA sequence analyses using small cell lung cancer cells and Ascl1-induced pulmonary neuroendocrine carcinoma cells. Histochem Cell Biol. 2020;153(6):443-456.
4. Wiedemeyer WR et al. ABBV-011, A Novel, Calicheamicin-Based Antibody–Drug Conjugate, Targets SEZ6 to Eradicate Small Cell Lung Cancer Tumors. Mol Cancer Ther. 2022;21:986-98.
5. Faivre E et al, AACR annual meeting 2024 AACR abstract #3148

OVERVIEW

IMGN151 is an investigational drug under clinical development. Safety and efficacy have not been established.

IMGN151 is a folate receptor alpha (FRα)-targeting antibody-drug conjugate in development for the treatment of ovarian and endometrial cancer. MGN151, comprises an asymmetric, bivalent, biparatopic antibody targeting two independent epitopes of FRα, linked to a maytansinoid derivative DM51 via a cleavable tri-peptide linker. The average drug per antibody ratio is 3.5.

PROPOSED MECHANISM OF ACTION^1,2

FRα is a member of a family of cell-surface glycoproteins that facilitate the transport and accumulation of folate, through endocytosis, into cells. FRα is overexpressed in multiple epithelial cancers including ovarian and endometrial and has limited expression on normal tissues.¹

IMGN151 is a next-generation anti-FRα ADC designed for enhanced payload delivery, cell killing, and bystander activity. IMGN151, is an asymmetric, bivalent, biparatopic antibody targeting two independent epitopes of FRα, linked to a highly potent maytansinoid derivative DM51 via a cleavable tri-peptide linker. The average drug per antibody ratio is 3.5. ^2,3

The clinical relevance of structure activity relationships has not been established.

DEVELOPMENT

IMGN151: DM21 Biparatropic FRα Antibody-Drug Conjugate is being investigated in a Phase 1 trial for the treatment of ovarian and endometrial cancer.

CLINICAL TRIALS

View select clinical trials with IMGN151: DM21 Biparatropic FRα Antibody-Drug Conjugate now. To view a full list of clinical trials in which IMGN151: DM21 Biparatropic FRα Antibody-Drug Conjugate is being investigated, please visit ClinicalTrials.gov.

1. Elnakat H, Ratnam M. Distribution, functionality and gene regulation of folate receptor isoforms: Implications in targeted therapy. Adv Drug Deliv Rev. 2004;56:1067-1084.
2. National Cancer Institute (NIH). NCI Drug Dictionary: anti-Fra/DM21 ADC IMGN151 (accessed July 2024):
   https://www.cancer.gov/publications/dictionaries/cancer-drug/def-opugotamig-olatansine
3. Lau J, et al. LC-MS based catabolite identification study of an ADC with DM21-C, a novel maytansinoid linker-payload. Abstract 538. AACR 2019.

OVERVIEW

Livmoniplimab is an investigational drug under clinical development. Safety and efficacy have not been established.

Livmoniplimab (ABBV-151) is a potential first-in-class humanized monoclonal antibody that is designed to bind to the GARP-TGF-β1 complex and is being investigated for the treatment of solid tumors, including non-small cell lung cancer (NSCLC), hepatocellular carcinoma (HCC), and ovarian granulosa cell tumors (OGCT).

PROPOSED MECHANISM OF ACTION

Livmoniplimab is an IgG4 monoclonal antibody designed to bind the GARP-TGF-β1 complex on the surface of Tregs, blocking the release of active TGF-β1 in the TME, a driver of immune escape. By blocking the inhibitory function of Tregs, livmoniplimab may overcome immune suppression and reinvigorate cytotoxic T cell immune mediated tumor cell killing.^1,2,3

DEVELOPMENT

Livmoniplimab is being investigated in Phase 2 studies in NSCLC, HCC, and OGCT.

Livmoniplimab was developed in partnership with Argenx.

CLINICAL TRIALS

View select clinical trials with ABBV-151 now. To view a full list of clinical trials in which ABBV-151 is being investigated, please visit ClinicalTrials.gov.

1. Metelli A, et al. Immunoregulatory functions and the therapeutic implications of GARP-TGF-β in inflammation and cancer. J Hematol Oncol. 2018; 11:24.
2. Metelli A, et al . Surface Expression of TGFβ Docking Receptor GARP Promotes Oncogenesis and Immune Tolerance in Breast Cancer. Cancer Res 2016; 76:7106–7117.
3. Cuende J, et al. Monoclonal antibodies against GARP/TGF-β1 complexes inhibit the immunosuppressive activity of human regulatory T cells in vivo. Sci Transl Med. 2015;7(284):284ra56.

OVERVIEW

Mirvetuximab soravtansine-gynx (MIRV, IMGN-853) is an approved drug being investigated for additional uses. Safety and efficacy have not been established for these additional uses.

Mirvetuximab soravtansine-gynx (MIRV, IMGN-853) is an antibody-drug conjugate (ADC) designed to target folate receptor alpha (FRᾳ)

PROPOSED MECHANISM OF ACTION^6,7

FRα is overexpressed in ovarian cancer and has minimal expression on normal tissues. MIRV is an ADC comprised of a humanized anti-FRa monoclonal antibody (M9346A) linked to a cytotoxic effector molecule, the maytansinoid DM4.^1,2 MIRV binds with high affinity and specificity to FRa, which upon antigen binding, promotes ADC internalization and intracellular release of DM4.³ Through its ability to inhibit tubulin polymerization and disrupt microtubule assembly, DM4 serves as a potent antimitotic agent to induce cell cycle arrest and apoptosis.⁴ Preclinically, MIRV has exhibited antitumor activity against FRa-expressing tumors, including models of ovarian cancer and NSCLC.⁵ In vitro, MIRV can display cytotoxic activity against cells situated near FRa-positive cells (bystander cytotoxic activity). This bystander activity can also affect neighboring healthy cells.⁵

DEVELOPMENT

MIRV is being investigated in platinum-sensitive ovarian cancer as a single agent and in combination with carboplatin and bevacizumab.

MIRVETUXIMAB SORAVTANSINE INDICATION AND SAFETY INFORMATION (US Prescribing Information)⁸

Indication:

• Mirvetuximab soravtansine is indicated for the treatment of adult patients with folate receptor-alpha (FRα) positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have received one to three prior systemic treatment regimens. Select patients for therapy based on an FDA-approved test. 

Boxed Warning OCULAR TOXICITY:

• Mirvetuximab soravtansine can cause severe ocular toxicities, including visual impairment, keratopathy, dry eye, photophobia, eye pain, and uveitis.
• Conduct an ophthalmic exam including visual acuity and slit lamp exam prior to initiation of mirvetuximab soravtansine, every other cycle for the first 8 cycles, and as clinically indicated.
• Administer prophylactic artificial tears and ophthalmic topical steroids.
• Withhold mirvetuximab soravtansine for ocular toxicities until improvement and resume at the same or reduced dose.
• Discontinue mirvetuximab soravtansine for Grade 4 ocular toxicities.

Warning and Precautions

• Ocular disorders: Mirvetuximab soravtansine can cause severe ocular adverse reactions, including visual impairment, keratopathy (corneal disorders), dry eye, photophobia, eye pain, and uveitis.
  Ocular adverse reactions occurred in 59% of patients with ovarian cancer treated with mirvetuximab soravtansine. Eleven percent (11%) of patients experienced Grade 3 ocular adverse reactions, including blurred vision, keratopathy (corneal disorders), dry eye, cataract, photophobia, and eye pain; two patients (0.3%) experienced Grade 4 events (keratopathy and cataract). The most common (≥5%) ocular adverse reactions were blurred vision (48%), keratopathy (36%), dry eye (27%), cataract (16%), photophobia (14%), and eye pain (10%).
  The median time to onset for first ocular adverse reaction was 5.1 weeks (range: 0.1 to 68.6). Of the patients who experienced ocular events, 53% had complete resolution; 38% had partial improvement (defined as a decrease in severity by one or more grades from the worst grade at last follow up). Ocular adverse reactions led to permanent discontinuation of mirvetuximab soravtansine in 1% of patients.
  Premedication and use of lubricating and ophthalmic topical steroid eye drops during treatment with mirvetuximab soravtansine are recommended. Advise patients to avoid use of contact lenses during treatment with mirvetuximab soravtansine unless directed by a healthcare provider.
  Refer patients to an eye care professional for an ophthalmic exam including visual acuity and slit lamp exam prior to treatment initiation, every other cycle for the first 8 cycles, and as clinically indicated. Promptly refer patients to an eye care professional for any new or worsening ocular signs and symptoms.
  Monitor for ocular toxicity and withhold, reduce, or permanently discontinue mirvetuximab soravtansine based on severity and persistence of ocular adverse reactions.
• Pneumonitis: Severe, life-threatening, or fatal interstitial lung disease (ILD), including pneumonitis, can occur in patients treated with mirvetuximab soravtansine.
  Pneumonitis occurred in 10% of patients treated with mirvetuximab soravtansine, including 1% with Grade 3 events and 1 patient (0.1%) with a Grade 4 event. One patient (0.1%) died due to respiratory failure in the setting of pneumonitis and lung metastases. One patient (0.1%) died due to respiratory failure of unknown etiology. Pneumonitis led to permanent discontinuation of mirvetuximab soravtansine in 3% of patients.
  Monitor patients for pulmonary signs and symptoms of pneumonitis, which may include hypoxia, cough, dyspnea, or interstitial infiltrates on radiologic exams. Infectious, neoplastic, and other causes for such symptoms should be excluded through appropriate investigations. Withhold mirvetuximab soravtansine for patients who develop persistent or recurrent Grade 2 pneumonitis until symptoms resolve to ≤ Grade 1 and consider dose reduction. Permanently discontinue mirvetuximab soravtansine in all patients with Grade 3 or 4 pneumonitis. Patients who are asymptomatic may continue dosing of mirvetuximab soravtansine with close monitoring.
• Peripheral neuropathy: Peripheral neuropathy occurred in 36% of patients with ovarian cancer treated with mirvetuximab soravtansine across clinical trials; 3% of patients experienced Grade 3 peripheral neuropathy. Peripheral neuropathy adverse reactions included peripheral neuropathy (20%), peripheral sensory neuropathy (9%), paraesthesia (6%), neurotoxicity (3%), hypoaesthesia (1%), peripheral motor neuropathy (0.9%), polyneuropathy (0.3%), and peripheral sensorimotor neuropathy (0.1%). Monitor patients for signs and symptoms of neuropathy, such as paresthesia, tingling or a burning sensation, neuropathic pain, muscle weakness, or dysesthesia.  For patients experiencing new or worsening PN, withhold dosage, dose reduce, or permanently discontinue mirvetuximab soravtansine based on the severity of PN.
• Embryo-fetal toxicity: Based on its mechanism of action, mirvetuximab soravtansine can cause embryo-fetal harm when administered to a pregnant woman because it contains a genotoxic compound (DM4) and affects actively dividing cells.
  Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with mirvetuximab soravtansine and for 7 months after the last dose.

Adverse Reactions

• The most common (≥20 %) adverse reactions, including lab abnormalities, were increased aspartate aminotransferase, fatigue, increased alanine aminotransferase, blurred vision, nausea, increased alkaline phosphatase, diarrhea, abdominal pain, keratopathy, peripheral neuropathy, musculoskeletal pain, decreased lymphocytes, decreased platelets, decreased magnesium, decreased hemoglobin, dry eye, constipation, decreased leukocytes, vomiting, decreased albumin, decreased appetite, and decreased neutrophils.

Drug Interactions

• DM4 is a CYP3A4 substrate. Closely monitor patients for adverse reactions with mirvetuximab soravtansine when used concomitantly with strong CYP3A4 inhibitors.

Use in Specific Populations

• Lactation: Advise women not to breastfeed during treatment with mirvetuximab soravtansine and for 1 month after the last dose.
• Hepatic Impairment: Avoid use of mirvetuximab soravtansine in patients with moderate or severe hepatic impairment (total bilirubin >1.5 ULN).

Review full US prescribing information for additional information at https://www.rxabbvie.com/

CLINICAL TRIALS

with mirvetuximab soravtansine now. To view a full list of clinical trials in which mirvetuximab soravtansine is being investigated, please visit ClinicalTrials.gov.

1. Lutz RJ. Targeting the folate receptor for the treatment of ovarian cancer. Transl Cancer Res. 2015;4:118-126.
2. Lambert JM. Drug-conjugated antibodies for the treatment of cancer. Br J Clin Pharmacol. 2013;76:248-262.
3. Erickson HK, Widdison WC, Mayo MF, et al. Tumor delivery and in vivo processing of disulfide-linked and thioether-linked antibody maytansinoid conjugates. Bioconjug Chem. 2010;21:84-92.
4. Hong EE, Erickson H, Lutz RJ, et al. Design of coltuximab ravtansine, a CD19-targeting antibody-drug conjugate (ADC) for the treatment of B-Cell malignancies: structure-activity relationships and preclinical evaluation. Mol Pharm. 2015;12:1703-1716.
5. Ab O, et al. IMGN853, a folate receptor-alpha (FRalpha)-targeting antibody-drug conjugate, exhibits potent targeted antitumor activity against FRalpha-expressing tumors. Mol Cancer Ther. 2015;14:1605-1613.
6. Moore KN, et al. Phase 1 Dose Escalation study of mirvetuximab soravtansine (IMGN853), a folate receptor alpha targeting antibody drug conjugate, in patients with solid tumors. Cancer. 2017;123(16):3080-3087.
7. Moore KN, et al. Mirvetuximab soravtansine in FRα-positive, platinum-resistant ovarian cancer. N Engl J Med. 2023;389:2162-2174.
8. Elahere. US Prescribing Information. March 2024.

OVERVIEW

Telisotuzumab vedotin (Teliso-V; ABBV-399) is an investigational drug under clinical development. Safety and efficacy have not been established.

Telisotuzumab vedotin (Teliso-V; ABBV-399) is an MMAE antibody-drug conjugate (ADC) designed to target c-Met composed of the ABT-700 (c-Met-targeting) antibody conjugated to the cytotoxic microtubule inhibitor monomethylauristatin E (MMAE) via a cleavable valine-citrulline (vc) linker.

PROPOSED MECHANISM OF ACTION

The c-Met receptor tyrosine kinase is the cell surface receptor for hepatocyte growth factor (HGF) encoded by the MET proto-oncogene. c-Met protein can be aberrantly activated in cancers contributing to tumor progression, angiogenesis, invasiveness, metastasis, and resistance.

c-Met inhibitors require MET amplification and/or MET activation for activity; however, as demonstrated in preclinical models, Teliso-V, an ADC designed to target c-Met protein, uses c-Met protein to deliver a cytotoxin to c-Met-protein-expressing cells, which enables cell killing regardless of reliance on MET signaling.¹ MET amplification can be a therapeutically actionable target, it generally occurs in 1% to 5% of de novo cancers.² c-Met protein expression may occur in up to 50% of solid tumors, depending on the thresholds used to determine protein overexpression.⁶

The c-Met protein can also be overexpressed in non-small cell lung cancer (NSCLC) and several other solid tumor types.1 In the LUMINOSITY Phase 2 trial pre-screening samples, c-Met protein overexpression, defined as strong 3+ staining in ≥25% of tumor cells, was observed in approximately 24% of cases. High c-Met protein overexpression, characterized by strong 3+ staining in ≥50% of tumor cells, was found in about 14% of cases. Teliso-V received accelerated approval within non-squamous advanced/metastatic NSCLC patients with high c-Met protein overexpression.3,4,5

Using an ADC that targets the c-Met protein offers a strategy independent of MET signaling pathway inhibition. This method delivers the potent cytotoxin MMAE directly to c-Met-expressing cells.²

DEVELOPMENT

Telisotuzumab vedotin-tllv is a c-Met-directed antibody and microtubule inhibitor conjugate indicated for the treatment of adult patients 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], as determined by an FDA-approved test, who have received a prior systemic therapy.⁵

This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).⁵

AbbVie continues to investigate Teliso-V in ongoing Phase 2 and Phase 3 trials in patients with previously treated c-Met-positive (by protein overexpression detected by immunohistochemistry) non-small cell lung cancer (NSCLC).

TELISOTUZUMAB VEDOTIN-TLLV INDICATION AND IMPORTANT SAFETY INFORMATION (US PRESCRIBING INFORMATION)⁵

INDICATION:

•        Telisotuzumab vedotin-tllv is a c-Met-directed antibody and microtubule inhibitor conjugate indicated for the treatment of adult patients 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], as determined by an FDA-approved test, who have received a prior systemic therapy.

•        This indication is approved under accelerated approval based on overall response rate (ORR) and duration of response (DOR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

IMPORTANT SAFETY INFORMATION

Peripheral Neuropathy
Telisotuzumab vedotin-tllv can cause peripheral neuropathy, including peripheral sensory neuropathy and peripheral motor neuropathy. In the safety population, peripheral neuropathy occurred in 51% of patients treated with Telisotuzumab vedotin-tllv, including Grade 3 in 11%. These adverse reactions included peripheral sensory neuropathy in 45% of patients and peripheral motor neuropathy in 9%. The median time to onset of peripheral neuropathy was 105 days (range: 1 to 472 days). Peripheral neuropathy led to permanent discontinuation of Telisotuzumab vedotin-tllv in 13% of patients. The median time to onset of peripheral neuropathy leading to treatment discontinuation was 249 days (range: 57 to 519 days). Of the 7 patients with motor neuropathy ongoing as of their last dose of Telisotuzumab vedotin-tllv, 6 had persistent Grade 1 or 2 symptoms 30 days after their last dose.

Monitor patients for signs and symptoms of new or worsening peripheral neuropathy such as hypoesthesia, hyperesthesia, paresthesia, a burning sensation, neuropathic pain, or muscle weakness. Withhold, reduce the dose, or permanently discontinue Telisotuzumab vedotin-tllv based on severity.

Interstitial Lung Disease/Pneumonitis
Telisotuzumab vedotin-tllv can cause severe, life-threatening, or fatal interstitial lung disease (ILD)/pneumonitis. In the safety population, ILD/pneumonitis occurred in 10% of patients treated with Telisotuzumab vedotin-tllv, including Grade 3 in 3% and Grade 4 in 0.6%. There were 3 fatal cases of ILD/pneumonitis in patients who received Telisotuzumab vedotin-tllv. The median time to onset of ILD/pneumonitis was 48 days (range: 23 to 85 days). ILD/pneumonitis led to permanent discontinuation of Telisotuzumab vedotin-tllv in 7% of patients. The median time to onset of ILD/pneumonitis leading to treatment discontinuation was 46 days (range: 23 to 85 days).

Advise patients to immediately report cough, dyspnea, fever, and/or any new or worsening respiratory symptoms. Monitor patients for signs and symptoms of ILD/pneumonitis. Withhold or permanently discontinue Telisotuzumab vedotin-tllv based on severity.

Ocular Surface Disorders
Telisotuzumab vedotin-tllv can cause ocular surface disorders, including blurred vision, visual impairment, keratitis, and dry eye. In the safety population, ocular surface disorders occurred in 25% of patients treated with Telisotuzumab vedotin-tllv. The most common ocular surface disorders were blurred vision (15%), keratitis (11%), and dry eye (5%). Grade 3 ocular surface disorders occurred in 1.2% of patients [blurred vision (1.2%), and keratitis (0.6%)]. The median time to onset of ocular surface disorders was 47 days (range: 1 to 319 days).

Monitor patients for ocular surface disorders during treatment with Telisotuzumab vedotin-tllv. Withhold Telisotuzumab vedotin-tllv and refer patients to an eye care professional for an ophthalmic examination and treatment for patients who develop Grade ≥2 ocular toxicity. Withhold or permanently discontinue Telisotuzumab vedotin-tllv based on severity.

Infusion-Related Reactions
Telisotuzumab vedotin-tllv can cause infusion-related reactions (IRR); signs and symptoms of IRR include dyspnea, flushing, chills, nausea, chest discomfort, and hypotension. The median time to onset of IRR was 28 days (range: 1 to 43 days). In the safety population, IRR occurred in 3% of patients treated with Telisotuzumab vedotin-tllv, including Grade 3 in 1.2% and Grade 4 in 0.6%. IRR led to permanent discontinuation of Telisotuzumab vedotin-tllv in 0.6% of patients.

Monitor patients for signs and symptoms of infusion reactions during Telisotuzumab vedotin-tllv infusion. Withhold, reduce the rate of infusion, or permanently discontinue Telisotuzumab vedotin-tllv based on severity. For patients who experience IRR, administer premedications prior to subsequent infusions.

Embryo-Fetal Toxicity
Based on the mechanism of action and findings in animals, Telisotuzumab vedotin-tllv can cause fetal harm when administered to a pregnant woman. The small molecule component of Telisotuzumab vedotin-tllv, monomethyl auristatin E (MMAE), administered to rats caused adverse developmental outcomes, including embryo-fetal mortality and structural abnormalities, at exposures similar to those occurring clinically at the recommended dose. 

Advise patients of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with Telisotuzumab vedotin-tllv and for 2 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with Telisotuzumab vedotin-tllv and for 4 months after the last dose.

Adverse Reactions
Serious adverse reactions occurred in 35% of patients. 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%) were decreased lymphocytes, increased glucose, increased alanine aminotransferase, increased gamma glutamyl transferase, decreased phosphorus, decreased sodium, decreased hemoglobin, and decreased calcium.

Drug Interactions
Strong CYP3A Inhibitors: Concomitant use with Telisotuzumab vedotin-tllv may increase the area under the curve of MMAE. Monitor for increased risk of adverse reactions to Telisotuzumab vedotin-tllv.

Use in Specific Populations
Severe or Moderate Hepatic Impairment: Avoid the use of Telisotuzumab vedotin-tllv.

Lactation: Advise lactating women not to breastfeed during treatment with Telisotuzumab vedotin-tllv and for 1 month after the last dose.

Infertility: Based on findings from animal studies, Telisotuzumab vedotin-tllv may impair fertility in females and males.

Review full prescribing information for additional information at www.rxabbvie.com or contact AbbVie Medical Information at 1-800-633-9110 or go to abbviemedinfo.com.

CLINICAL TRIALS

View select clinical trials with Teliso-V now. To view a full list of clinical trials in which Teliso-V is being investigated, please visit ClinicalTrials.gov.

References

1. Wang J, Anderson MG, Oleksijew A, et al. ABBV-399, a c-Met antibody-drug conjugate that targets both MET-amplified and c-Met-overexpressing tumors, irrespective of MET pathway dependence. Clin Cancer Res. 2017;23(4):992-1000.
2. Strickler JH, et al. First-in-human phase i, dose-escalation and -expansion study of telisotuzumab vedotin, an antibody–drug conjugate targeting c-Met, in patients with advanced solid tumors. J Clin Oncol. 2018;36(33):3298-3306.
3. Ansell PJ, Baijal S, Liede A, et al. Prevalence and characterization of c-MET–overexpressing non-small cell lung cancer (NSCLC) across clinical trial samples and real-world patient cohorts from the City of Hope National Medical Center. Poster presented at: Cancer Research UK (CRUK) – Lung Cancer Conference. Manchester, UK; 2022.
4. Liang H, Wang M. MET oncogene in non-small cell lung cancer: Mechanism of MET dysregulation and agents targeting the HGF/c-Met axis. Onco Targets Ther. 2020;13:2491-2510.
5. Telisotuzumab vedotin US Prescribing Information. May 2025.
6. Salgia R. MET in Lung Cancer: Biomarker Selection Based on Scientific Rationale. Mol Cancer Ther 2017; 16:555–565.

OVERVIEW

TTX-030 is an investigational drug under clinical development. Safety and efficacy have not been established.

TTX-030 is an anti-CD39 monoclonal antibody that is being investigated in pancreatic cancer.

PROPOSED MECHANISM OF ACTION^1,2

In solid tumors, ATP is abundantly released in the extracellular space, leading to an accumulation of eATP levels far in excess of those found in healthy tissues. Extracellular ATP acts as a proinflammatory stimulus by agonizing P2 purinergic receptors in immune cells.

Tumors are proficient at scavenging eATP and converting it to immunosuppressive adenosine by means of two ectonucleotidases, CD39 and CD73. CD39 hydrolyzes eATP, converting it to adenosine monophosphate (AMP); AMP can in turn be converted to adenosine by CD73.  Adenosine acts on P1 receptors found ubiquitously on immune cells, causing immunosuppression; therefore has anti-inflammatory effects.

TTX-030 inhibits CD39 enzymatic activity, thus preventing hydrolysis of proinflammatory ATP to immunosupressive adenosine and resulting in a preservation of immune cell function and tumor clearance.

DEVELOPMENT

TTX-030 is being investigated as a monotherapy and in combination with a PD1 inhibitor and/or chemotherapy in patients with pancreatic cancer.

*TTX-030 developed by Trishula Therapeutics through Phase 1b and AbbVie has option to lead global development

CLINICAL TRIALS

View select clinical trials with TTX-030 now. To view a full list of clinical trials in which TTX-030 is being investigated, please visit ClinicalTrials.gov.

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