Camtobell (belotecan) / Chong Kun Dang - LARVOL DELTA

Investigational DNA topoisomerase I inhibitors for colorectal cancer: preclinical and early phase developments. (PubMed, Expert Opin Investig Drugs) - "Despite the success of CPT derivatives like irinotecan, topotecan and belotecan (approved drugs), drawbacks such as lactone instability have led to the development of modified compounds. Dual inhibitors, combination therapies, integration with immunotherapy and personalized medicine further enhances treatment efficacy. Ongoing preclinical studies offer hope for improved CRC management."

Journal • Preclinical • Review • Colorectal Cancer • Oncology • Solid Tumor

Results of a phase 1/2 study of sacituzumab tirumotecan in patients with unresectable locally advanced or metastatic solid tumors refractory to standard therapies. (PubMed, J Hematol Oncol) - P1/2 | "Sac-TMT demonstrated manageable safety profile in patients with unresectable locally advanced/metastatic solid tumors and promising antitumor activity in metastatic TNBC and HR+/HER2 - breast cancer. Sac-TMT is being investigated in phase 3 studies."

Journal • P1/2 data • Breast Cancer • Dental Disorders • Dermatology • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Immunology • Oncology • Solid Tumor • Stomatitis • Triple Negative Breast Cancer • Urticaria • HER-2

Sacituzumab tirumotecan (sac-TMT) as first-line treatment for unresectable locally advanced/metastatic triple-negative breast cancer (a/mTNBC): Initial results from the phase II OptiTROP-Breast05 study. (ASCO 2025) - P2, P3 | "Sac-TMT (MK-2870/SKB264) is a TROP2 ADC developed with a novel linker to conjugate the payload, a belotecan-derivative topoisomerase I inhibitor. Sac-TMT demonstrated promising anti-tumor activity with a manageable safety profile as a first-line treatment for pts with a/mTNBC, independent of the PD-L1 status. A Phase 3 study comparing sac-TMT vs investigator's choice of chemotherapy in first-line PD-L1-negative (CPS < 10) a/mTNBC is currently underway (NCT06279364)."

Clinical • Metastases • P2 data • Anemia • Breast Cancer • Dental Disorders • Fatigue • Interstitial Lung Disease • Oncology • Pain • Pneumonia • Pulmonary Disease • Respiratory Diseases • Solid Tumor • Stomatitis • Triple Negative Breast Cancer

Sacituzumab tirumotecan (sac-TMT) in combination with tagitanlimab (anti-PD-L1) in first-line (1L) advanced non-small-cell lung cancer (NSCLC): Non-squamous cohort from the phase II OptiTROP-Lung01 study. (ASCO 2025) - P2, P3 | "Clinical Trial Registration Number: NCT05351788 Background: Sac-TMT (MK-2870/SKB264) is a TROP2 ADC developed with a novel linker to conjugate a belotecan-derivative topoisomerase I inhibitor. Sac-TMT in combination with tagitanlimab demonstrated promising antitumor activity in treatment-naive advanced non-squamous NSCLC. The durable clinical activities were observed regardless of PD-L1 expression. This combination therapy showed a tolerable safety profile based on known profiles of the individual agents, with no new safety signals observed."

Clinical • Combination therapy • IO biomarker • Metastases • P2 data • Anemia • Dental Disorders • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Stomatitis

Sacituzumab tirumotecan (sac-TMT) in patients (pts) with previously treated locally advanced or metastatic (LA/M) non-small cell lung cancer (NSCLC) harboring uncommon EGFR mutations: Preliminary results from a phase 2 study. (ASCO 2025) - P2 | "Sac-TMT (MK-2870/SKB264) is a TROP2 ADC developed with a hydrolytically cleavable linker to conjugate a belotecan-derivative topoisomerase I inhibitor. Sac-TMT monotherapy demonstrated promising clinical activity with a manageable safety profile in previously treated advanced NSCLC pts with uncommon EGFR mutations. These findings warrant further investigation of sac-TMT as a potential therapy for this population."

Clinical • Metastases • P2 data • Anemia • Dental Disorders • Interstitial Lung Disease • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pneumonia • Pulmonary Disease • Respiratory Diseases • Solid Tumor • Stomatitis • EGFR

Sacituzumab tirumotecan (sac-TMT) in patients (pts) with previously treated advanced EGFR-mutated non-small cell lung cancer (NSCLC): Results from the randomized OptiTROP-Lung03 study. (ASCO 2025) - P2 | "Clinical Trial Registration Number: NCT05631262 Background: Sac-TMT (MK-2870/SKB264), a novel TROP2 ADC developed to conjugate a belotecan-derivative topoisomerase I inhibitor, has shown encouraging antitumor activity in EGFRm NSCLC pts in phase Ⅰ trial (Fang et al. Sac-TMT demonstrated improved ORR, PFS and OS compared to docetaxel, with manageable safety profile in pts with previously treated advanced EGFRm NSCLC. These results highlight significant survival benefits and suggest that sac-TMT could emerge as a new standard of care for this population."

Clinical • Metastases • Anemia • Dental Disorders • Febrile Neutropenia • Lung Cancer • Neutropenia • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Stomatitis • EGFR

KEYMAKER-U01E: A phase 2 umbrella study with rolling arms of investigational agents with or without chemotherapy plus pembrolizumab for resectable stage II–IIIB (N2) non–small-cell lung cancer (NSCLC). (ASCO 2025) - P2 | "Sacituzumab tirumotecan (sac-TMT/MK-2870/SKB264) is an antibody-drug conjugate composed of an anti-trophoblast cell surface antigen 2 antibody, a hydrolytically cleavable linker, and a belotecan-derivative topoisomerase I inhibitor payload (average drug-to-antibody ratio, 7.4)...In Arm 1 (reference arm), pts will receive neoadjuvant therapy of 4 cycles of pembro 200 mg intravenously (IV) + CT IV Q3W (cisplatin 75 mg/m2 or carboplatin area under the curve 5 or 6 mg/mL/min on day 1 with gemcitabine 1000 mg/m2 on days 1 and 8 for squamous histology, with pemetrexed 500 mg/m2 on day 1 for nonsquamous, or with paclitaxel 175 or 200 mg/m2 on day 1 for any histology)...AEs will be graded per NCI CTCAE v5.0. Enrollment is scheduled to begin in March 2025 at 34 sites globally."

P2 data • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Intravesical sacituzumab tirumotecan in participants with intermediate-risk non–muscle-invasive bladder cancer: The phase 1/2 TroFuse-027 study. (ASCO 2025) - P1/2 | "Sacituzumab tirumotecan (sac-TMT; MK-2870) is an antibody-drug conjugate consisting of a humanized anti-TROP2 monoclonal antibody, a linker, and a cytotoxic belotecan-derivative topoisomerase I inhibitor...Secondary objectives are pharmacokinetics and complete response rate (the proportion of participants with the absence of visible tumors at the 12-week assessment after initiating treatment) and duration of complete response per local assessment. Future studies (phase 2) will be initiated on completion of dose escalation and based on the totality of data."

P1/2 data • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

A phase 3, randomized study of adjuvant sacituzumab tirumotecan plus pembrolizumab vs treatment of physician's choice in participants with triple-negative breast cancer who received neoadjuvant therapy and did not achieve a pathologic complete response at surgery. (ASCO 2025) - P3 | "Sacituzumab tirumotecan (sac-TMT; also known as MK-2870/SKB264) is a novel antibody-drug conjugate composed of anti-TROP2 antibody coupled to a cytotoxic belotecan derivative via a novel linker (average drug/antibody ratio, 7.4)...This study (NCT06393374) evaluates adjuvant sac-TMT + pembrolizumab vs treatment of physician's choice (TPC; pembrolizumab ± capecitabine) in participants with TNBC who received neoadjuvant therapy and did not achieve pCR at surgery...Secondary endpoints are OS, distant recurrence-free survival, patient-reported outcomes, and safety. Enrollment began Q2 2024."

Clinical • P3 data • Surgery • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • TACSTD2

Trofuse-023: A phase 3, randomized, open-label study of pembrolizumab with or without maintenance sacituzumab tirumotecan (sac-TMT) as first-line treatment for metastatic squamous non-small-cell lung cancer (NSCLC) (AACR 2025) - "Sac-TMT (also known as MK-2870/SKB264) is an antibody-drug conjugate composed of an anti-TROP2 antibody coupled to a belotecan-derivative topoisomerase I inhibitor KL610023 (drug-to-antibody ratio, 7.4) via a novel linker...Patients will receive induction of pembrolizumab (200 mg IV Q3W) plus chemotherapy (carboplatin AUC 6 mg/mL/min IV Q3W and paclitaxel 200 mg/m2 IV Q3W or nab-paclitaxel 100 mg/m2 IV weekly) for 4 cycles...Other secondary endpoints include safety and patient-reported outcomes. Enrollment began on June 10, 2024, and the study is ongoing globally with 210 planned sites."

Clinical • IO biomarker • Metastases • P3 data • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • TACSTD2

Development of antibody drug conjugates targeting MUC16 in ovarian cancer subtypes (AACR 2025) - "To exploit this target, we have systematically evaluated a panel of ADC payloads and linkers, including Auristatins (MMAE, MMAF), Camptothecin (SN-38), Maytansinoids, Calicheamicin, Nemorubicin, and Belotecan, conjugated to our proprietary antibody 4H11. The retained portion of MUC16 is a viable target for ADC development. The maytansinoid conjugates emerged as leading candidates for further preclinical evaluation and potential clinical development based on their broad spectrum of activity against multiple histological subtypes. Our findings further underscore preferential susceptibility of different OC histologic subtypes to different ADC payloads."

High Grade Serous Ovarian Cancer • Oncology • Ovarian Cancer • Solid Tumor • MUC16

A Phase 3 Randomized Study of Adjuvant Sacituzumab Tirumotecan Plus Pembrolizumab vs Treatment of Physician's Choice in Patients With Triple-Negative Breast Cancer Who Received Neoadjuvant Therapy and Did Not Achieve a Pathological Complete Response at Surgery (MBCC 2025) - P3 | "Sacituzumab tirumotecan (also known as MK-2870/SKB264) is a novel antibody-drug conjugate composed of anti-TROP2 antibody coupled to a cytotoxic belotecan derivative via a novel linker (average drug/antibody ratio, 7.4)...This study (NCT06393374) evaluates adjuvant sacituzumab tirumotecan plus pembrolizumab vs treatment of physician's choice (pembrolizumab ± capecitabine) in patients with TNBC who received neoadjuvant therapy and did not achieve pCR at surgery...Secondary end points are OS, distant recurrence-free survival, patient-reported outcomes, and safety. Status Enrollment began in Q2 2024."

Clinical • P3 data • Surgery • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • TACSTD2

Phase 3, Randomized, Open-Label TroFuse-010 Study of Sacituzumab Tirumotecan Alone and With Pembrolizumab Versus Treatment of Physician's Choice Chemotherapy in Patients With HR+/ HER2– Unresectable Locally Advanced or Metastatic Breast Cancer (MBCC 2025) - P3 | "Sacituzumab tirumotecan (sac-TMT; MK-2870/SKB264) is a novel anti-TROP2 antibody-drug conjugate composed of an anti-TROP2 antibody coupled to a cytotoxic belotecan derivative via a novel linker (average drug/ antibody ratio, 7.4)...Patients are randomized 3:3:2 to intravenous sac-TMT 4 mg/kg every 2 weeks, intravenous sac-TMT 4 mg/kg every 2 weeks plus pembrolizumab 400 mg every 6 weeks, or physician's choice chemotherapy (paclitaxel, nab-paclitaxel, capecitabine, or liposomal doxorubicin) until radiographic PD, unacceptable toxicity, patient withdrawal, or discontinuation criteria are met...Secondary endpoints include OS, PFS per RECIST v1.1 by BICR with sac-TMT plus pembrolizumab vs sac-TMT, overall response rate, duration of response, patient-reported outcomes, and safety. Status Active recruitment is ongoing."

Clinical • IO biomarker • Metastases • P3 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2 • PD-L1 • TACSTD2

HIRA to remove…drugs from Group 2 anticancer list, update reimbursement criteria (Korea Biomedical Review) - "The move, which is aimed at overhauling the reimbursement system and reflecting the latest clinical evidence, will take effect on March 1. The drugs that will be deleted from the list of Group 2 anticancer drugs are albumin-bound paclitaxel, aldesleukin(IL- 2), anagrelide, anastrozole, belotecan, capecitabine..."

Reimbursement • Oncology

Phase 1/2 study of the trophoblast cell surface antigen 2 (TROP2) antibody-drug conjugate (ADC) sacituzumab tirumotecan (sac-TMT) as monotherapy or combination therapy in gastrointestinal cancers: LIGHTBEAM-02A. (ASCO-GI 2025) - P1/2 | "Sac-TMT (formerly MK-2870/SKB264) is an ADC consisting of a humanized antihuman TROP2 monoclonal antibody, a linker, and a cytotoxic belotecan–derivative topoisomerase I inhibitor...Cohort 1 is included in a dose-escalation phase to determine the recommended phase 2 dose of sac-TMT when used in combination with fluorouracil and leucovorin and an efficacy phase...Secondary objectives are to evaluate duration of response and progression-free survival per RECIST v1.1 by BICR and overall survival. Enrollment is ongoing."

Combination therapy • Monotherapy • P1/2 data • Biliary Cancer • Biliary Tract Cancer • Colorectal Adenocarcinoma • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • TACSTD2

Repurposing FDA-approved drugs to target G-quadruplexes in breast cancer. (PubMed, Eur J Med Chem) - "Notably, belotecan and irinotecan exhibited a synergistic mechanism, combining G4 stabilization with their established topoisomerase I inhibition activity to enhance cytotoxicity in cancer cells. Our findings support the therapeutic potential of G4 stabilization in breast cancer, validate drug repurposing as an efficient strategy to identify G4-targeting drugs, and highlight how combining G4 stabilization with other established drug activities may improve anticancer efficacy."

FDA event • Journal • Breast Cancer • Oncology • Solid Tumor • TOP1

Phase 3, Randomized, Open-label TroFuse-010 Study of Sacituzumab Tirumotecan (sac-TMT) Alone & W/ Pembrolizumab vs. Treatment of Physician's Choice Chemotherapy in Patients With HR+/HER2- Unresectable Locally Advanced or Metastatic Breast Cancer (SABCS 2024) - P3 | "Sac-TMT (also known as MK-2870/SKB264) is a novel anti-TROP2 antibody-drug conjugate composed of an anti-TROP2 antibody coupled to a cytotoxic belotecan derivative via a novel linker (average drug/antibody ratio, 7.4)...Patients are randomized 3:3:2 to receive IV sac-TMT 4 mg/kg Q2W, IV sac-TMT 4 mg/kg Q2W plus pembrolizumab 400 mg Q6W, or TPC (paclitaxel, nab-paclitaxel, capecitabine, or liposomal doxorubicin) until radiographic PD, unacceptable toxicity, patient withdrawal, or discontinuation criteria are met...Tumor imaging occurs at baseline, Q9W through week 54, and Q12W thereafter. Recruitment began in April 2024."

Clinical • IO biomarker • Metastases • P3 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2 • PD-L1 • TACSTD2

A Phase 3, Randomized Study of Adjuvant Sacituzumab Tirumotecan (sac-TMT) Plus Pembrolizumab vs. Treatment of Physician's Choice in Patients With TNBC Who Received Neoadjuvant Therapy & Did Not Achieve a Pathological Complete Response at Surgery (SABCS 2024) - P3 | "Sacituzumab tirumotecan (also known as sac-TMT/MK-2870/SKB264) is a novel antibody-drug conjugate composed of anti-TROP2 antibody coupled to a cytotoxic belotecan derivative via a novel linker with an average drug to antibody ratio of 7.4...The current study (NCT06393374) evaluates adjuvant sac-TMT plus pembrolizumab versus treatment of physician's choice (TPC; comprised of pembrolizumab with or without capecitabine) in patients with TNBC who received neoadjuvant therapy and did not achieve a pCR at surgery...Secondary endpoints are overall survival (OS), distant recurrence-free survival (DRFS), patient-reported outcomes (PROs), and safety. Enrollment began in Q2 2024."

Clinical • P3 data • Surgery • Breast Cancer • Triple Negative Breast Cancer • TACSTD2

A phase III, randomized study of adjuvant sacituzumab tirumotecan (sac-TMT) plus pembrolizumab vs treatment of physician's choice (TPC) in patients with TNBC who received neoadjuvant therapy and did not achieve a pathological complete response (pCR) at surgery (ESMO Asia 2024) - P3 | "Sac-TMT (MK-2870/SKB264) is a novel ADC composed of anti-TROP2 antibody coupled to a cytotoxic belotecan derivative via a novel linker (average drug/antibody ratio, 7.4)...This study (NCT06393374) evaluates adjuvant sac-TMT + pembro vs TPC (pembro ± capecitabine) in pts with TNBC who received neoadjuvant therapy and did not achieve pCR at surgery...Secondary endpoints are OS, distant recurrence-free survival, PROs, and safety. Enrollment began Q2 2024."

Clinical • P3 data • Surgery • Oncology • Triple Negative Breast Cancer • TACSTD2

TroFuse-015: A phase III study of trophoblast antigen 2 (TROP2)–directed antibody-drug conjugate sacituzumab tirumotecan (sac-TMT) vs treatment of physician's choice (TPC) for previously treated metastatic gastroesophageal adenocarcinoma (GEA) (ESMO Asia 2024) - P1/2, P3 | "Sac-TMT (also known as MK-2870/SKB264) is a TROP2-directed antibody-drug conjugate developed with a novel linker to a belotecan-derivative topoisomerase I inhibitor...Approximately 450 patients will be randomly assigned (1:1) to receive sac-TMT 4 mg/kg IV on days 1, 15, and 29 of every 42-day cycle or TPC (TAS-102 [35 mg/m 2 by mouth (PO) twice daily (BID) on days 1-5 and 8-12 of every 28-day cycle]; irinotecan [150 mg/m 2 IV on days 1 and 15 of every 28-day cycle]; paclitaxel [80 mg/m 2 IV on days 1, 8, and 15 of every 28-day cycle]; or docetaxel [75 mg/m 2 IV on day 1 of every 21-day cycle])...Secondary end points are PFS, ORR, and DOR (all per RECIST v1.1 by BICR), safety, and tolerability. Enrollment is currently ongoing."

Metastases • P3 data • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • TACSTD2

Pharmacokinetics, toxicities, and tissue concentrations of belotecan sprayed by rotational intraperitoneal pressurized aerosol chemotherapy in a pig model. (PubMed, J Gynecol Oncol) - "RIPAC using belotecan of 0.5 mg/m² and 1.5 mg/m² may be feasible with fewer hepatic and renal toxicities in pigs. Thus, belotecan of 1.5 mg/m² may be considered as the starting dose for RIPAC in a phase 1 trial."

Journal • PK/PD data • Preclinical

Seminal Abstract: Efficacy and Safety of Sacituzumab Tirumotecan (sac-TMT) Plus Pembrolizumab in Patients with Recurrent or Metastatic Cervical Cancer (IGCS 2024) - P2 | "Sac-TMT (also known as MK-2870/ SKB264) is a TROP2 ADC developed with novel linker to conjugate a belotecan-derivative topoisomerase I inhibitor...47.4% had received two prior lines of therapy, 52.6% had received bevacizumab, and 42.1% had received anti-PD-1 based therapy...No new safety signal was observed. Considering the activity of this combination among pts who were pre-treated with anti-PD-1 based therapy, further investigation is warranted."

Clinical • Metastases • Cervical Cancer • Oncology • Solid Tumor

Efficacy and safety of sacituzumab tirumotecan (sac-TMT) plus pembrolizumab in patients with recurrent or metastatic cervical cancer (ESMO 2024) - P2 | "Sac-TMT (also known as MK-2870/ SKB264) is a TROP2 ADC developed with novel linker to conjugate a belotecan-derivative topoisomerase I inhibitor...47.4% had received two prior lines of therapy, 52.6% had received bevacizumab, and 42.1% had received anti-PD-1 based therapy... Sac-TMT plus pembrolizumab demonstrated promising and durable antitumor activity with manageable safety profile. No new safety signal was observed. Considering the activity of this combination among pts who were pre-treated with anti-PD-1 based therapy, further investigation is warranted."

Clinical • Metastases • Cervical Cancer • Oncology • Solid Tumor

PHASE 3 ENGOT-EN23/GOG-3095/MK-2870-005 STUDY: SACITUZUMAB TIRUMOTECAN (SAC-TMT) MONOTHERAPY VS TREATMENT OF PHYSICIAN'S CHOICE CHEMOTHERAPY IN PATIENTS WITH ENDOMETRIAL CANCER WHO RECEIVED PRIOR CHEMOTHERAPY AND IMMUNOTHERAPY (IGCS 2024) - P3 | "Sac-TMT (also known as MK-2870/SKB264) is a novel antibody-drug conjugate composed of an anti-TROP2 antibody coupled to a cytotoxic belotecan derivative via a novel linker (average drug/antibody ratio, 7.4)...Patients are randomized 1:1 to receive intravenous sac-TMT 4 mg/kg Q2W or TPC (doxorubicin 60 mg/m2 Q3W [21-day cycle] or paclitaxel 80 mg/m2 on days 1, 8, and 15 Q4W [28-day cycle]) until radiographic PD, unacceptable toxicity, or patient withdrawal...Imaging assessments occur Q8W from randomization through week 56 and Q12W thereafter. Current Trial Status: Enrollment began in Dec 2023"

Clinical • IO biomarker • Monotherapy • P3 data • Endometrial Cancer • Oncology • Sarcoma • Solid Tumor • TACSTD2

Phase III, randomized, open-label TroFuse-010 Study of sacituzumab tirumotecan (sac-TMT) alone and with pembrolizumab vs treatment of physician's choice chemotherapy (TPC) in patients with HR+/HER2- unresectable locally advanced or metastatic breast cancer (mBC) (ESMO 2024) - P3 | "Sac-TMT (also known as MK-2870/SKB264) is a novel anti-TROP2 antibody-drug conjugate composed of an anti-TROP2 antibody coupled to a cytotoxic belotecan derivative via a novel linker (average drug/antibody ratio, 7.4)...Pts are randomized 3:3:2 to receive IV sac-TMT 4 mg/kg Q2W, IV sac-TMT 4 mg/kg Q2W + pembro 400 mg Q6W, or TPC (paclitaxel, nab-paclitaxel, capecitabine, or liposomal doxorubicin) until radiographic PD, unacceptable toxicity, pt withdrawal, or discontinuation criteria are met...Secondary endpoints include OS, PFS per RECIST v1.1 by BICR with sac-TMT + pembro vs sac-TMT, ORR, DOR, PROs, and safety. Recruitment began in April 2024."

Clinical • IO biomarker • Metastases • P3 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2 • PD-L1 • TACSTD2