Cometriq (cabozantinib capsule) / Exelixis, Ipsen, Takeda, Royalty - LARVOL DELTA

NRG-GU012: RANDOMIZED PHASE II STEREOTACTIC ABLATIVE RADIATION THERAPY (SABR) FOR METASTATIC UNRESECTED RENAL CELL CARCINOMA (RCC) RECEIVING IMMUNOTHERAPY (SAMURAI) (KCRS 2023) - "P2 | N=240 | SAMURAI (NCT05327686) | Sponsor: NRG Oncology; "To detect a hazard ratio of 0.62, which corresponds under exponential distribution assumptions to an absolute 15% improvement in one-year nrPFS from 50% in the control group to 65% in the experimental arm (SABR plus immunotherapy), a total sample size of 240 patients will be enrolled. This design will provide 90% power, based on a one-sided logrank test at the 0.05 alpha level, with three years of accrual and two further years of follow-up. The expected number of nrPFS events is E=175. The calculations allow for a 10% non-eligible/early dropout rate. The trial is currently open and accruing through the NRG oncology cooperative group (NCT05327686)."

Clinical • Metastases • P2 data • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

A Randomized, Double-Blind Noninferiority Study to Evaluate the Efficacy of the Cabozantinib Tablet at 60 mg per Day Compared with the Cabozantinib Capsule at 140 mg per Day in Patients With Progressive, Metastatic Medullary Thyroid Cancer. (PubMed, Thyroid) - P4 | "The 60-mg/day tablet had the same ORR and lower rates of AEs. Clinical trial registry: ClinicalTrials.gov NCT01896479."

Clinical • Head-to-Head • Journal • Endocrine Cancer • Neuroendocrine Tumor • Oncology • Solid Tumor • Thyroid Gland Carcinoma • Thyroid Gland Medullary Carcinoma

A Phase II Study of Nivolumab with Ipilimumab and Cabozantinib in Patients with Untreated Renal Cell Carcinoma Brain Metastases (SNO-ASCO-CNS 2024) - No abstract available.

Renal Cell Carcinoma

NF113: Study of Cabozantinib With Selumetinib for Plexiform Neurofibromas (clinicaltrials.gov) - P1 | N=30 | Recruiting | Sponsor: Girish Dhall, MD | Not yet recruiting ➔ Recruiting

Enrollment open • Genetic Disorders • Neurofibromatosis • Solid Tumor • NF1

Modulation of the Bone Immune Microenvironment Following Cabozantinib Treatment of Bone Metastatic Clear Cell Renal Cell Carcinoma: Proof of Concept Study (clinicaltrials.gov) - P1 | N=16 | Recruiting | Sponsor: M.D. Anderson Cancer Center | Not yet recruiting ➔ Recruiting

Enrollment open • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Cabozantinib S-malate in Treating Patients With Relapsed Osteosarcoma or Ewing Sarcoma (clinicaltrials.gov) - P2 | N=90 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Jul 2026 ➔ Jul 2027

Trial completion date • Ewing Sarcoma • Oncology • Osteosarcoma • Sarcoma • Solid Tumor

Cabozantinib S-malate and Nivolumab in Treating Patients With Advanced, Recurrent, or Metastatic Endometrial Cancer (clinicaltrials.gov) - P2 | N=82 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Jul 2026 ➔ Jul 2027

dMMR • IO biomarker • MSI-H • pMMR • Trial completion date • Carcinosarcoma • Endometrial Cancer • Oncology • Sarcoma • Solid Tumor • Uterine Cancer

Cabozantinib Franchise Highlights (Businesswire) - "Net product revenues generated by the cabozantinib franchise in the U.S. were $573.0 million during the second quarter of 2026, with net product revenues of $570.6 million from CABOMETYX (cabozantinib) and $2.4 million from COMETRIQ (cabozantinib). Based upon cabozantinib-related net product revenues generated by Exelixis’ collaboration partners, Ipsen and Takeda Pharmaceutical Company Limited, during the quarter ended June 30, 2026, Exelixis earned $53.2 million in royalty revenues."

Sales • Hepatocellular Cancer • Neuroendocrine Tumor • Pancreatic Cancer • Renal Cell Carcinoma • Thyroid Gland Medullary Carcinoma • Urothelial Cancer

Using Nivolumab Alone or With Cabozantinib to Prevent Mucosal Melanoma Return After Surgery (clinicaltrials.gov) - P2 | N=101 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Sep 2026 ➔ Jul 2027 | Trial primary completion date: Sep 2026 ➔ Jul 2027

Trial completion date • Trial primary completion date • Melanoma • Mucosal Melanoma • Oncology • Solid Tumor • PD-L1

Cabozantinib In Combo With NIVO + IPI In Advanced NCCRCC (clinicaltrials.gov) - P2 | N=60 | Active, not recruiting | Sponsor: Bradley A. McGregor, MD | Trial completion date: Dec 2026 ➔ Jun 2027 | Trial primary completion date: Jun 2026 ➔ Dec 2026

Trial completion date • Trial primary completion date • Genito-urinary Cancer • Non Clear Cell Renal Cell Carcinoma • Oncology • Papillary Renal Cell Carcinoma • Renal Cell Carcinoma • Solid Tumor

ADVL1622: Cabozantinib-S-Malate in Treating Younger Patients With Recurrent, Refractory, or Newly Diagnosed Sarcomas, Wilms Tumor, or Other Rare Tumors (clinicaltrials.gov) - P2 | N=109 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Jun 2026 ➔ Jun 2027

Trial completion date • Adrenal Cortex Carcinoma • Alveolar Soft Tissue Sarcoma • Brain Cancer • Clear Cell Renal Cell Carcinoma • CNS Tumor • Ewing Sarcoma • Genito-urinary Cancer • Hepatoblastoma • Hepatocellular Cancer • Nephrology • Oncology • Osteosarcoma • Renal Cell Carcinoma • Rhabdomyosarcoma • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Thyroid Gland Carcinoma • Thyroid Gland Medullary Carcinoma • Wilms Tumor • AXL • MET • RET

Ph II Study of Cabozantinib With Pembrolizumab in Metastatic Gastric and Gastroesophageal Adenocarcinoma (clinicaltrials.gov) - P2 | N=34 | Completed | Sponsor: University of California, Irvine | Active, not recruiting ➔ Completed | Trial completion date: May 2026 ➔ Sep 2025

Trial completion • Trial completion date • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Adenocarcinoma • Gastric Cancer • Gastroesophageal Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • Solid Tumor • PD-L1

Autologous Dendritic Cell Vaccine in Kidney Cancer (clinicaltrials.gov) - P2 | N=42 | Recruiting | Sponsor: Jodi Maranchie | Trial completion date: Dec 2026 ➔ Dec 2027 | Trial primary completion date: Dec 2026 ➔ Dec 2027

Trial completion date • Trial primary completion date • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Testing the Effectiveness of Two Immunotherapy Drugs (Nivolumab and Ipilimumab) With One Anti-cancer Targeted Drug (Cabozantinib) for Rare Genitourinary Tumors (clinicaltrials.gov) - P2 | N=314 | Recruiting | Sponsor: National Cancer Institute (NCI) | N=224 ➔ 314

Enrollment change • Bladder Cancer • Clear Cell Renal Cell Carcinoma • Endocrine Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Kidney Medullary Carcinoma • Lung Cancer • Nasopharyngeal Carcinoma • Neuroendocrine Tumor • Oncology • Penile Cancer • Prostate Cancer • Renal Cell Carcinoma • Sarcoma • Solid Tumor • Squamous Cell Carcinoma • Testicular Cancer • Urethral Cancer • Urothelial Cancer • CD4 • PD-L1

Testing the Effectiveness of Two Immunotherapy Drugs (Nivolumab and Ipilimumab) With One Anti-cancer Targeted Drug (Cabozantinib) for Rare Genitourinary Tumors (clinicaltrials.gov) - P2 | N=314 | Recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Feb 2025 ➔ Feb 2026 | Trial primary completion date: Feb 2025 ➔ Feb 2026

Trial completion date • Trial primary completion date • Bladder Cancer • Clear Cell Renal Cell Carcinoma • Endocrine Cancer • Genito-urinary Cancer • Kidney Medullary Carcinoma • Large Cell Carcinoma • Lung Cancer • Nasopharyngeal Carcinoma • Neuroendocrine Tumor • Oncology • Papillary Renal Cell Carcinoma • Penile Cancer • Prostate Cancer • Renal Cell Carcinoma • Sarcoma • Solid Tumor • Squamous Cell Carcinoma • Testicular Cancer • Urethral Cancer • Urothelial Cancer • CD4 • PD-L1

Testing the Effectiveness of Two Immunotherapy Drugs (Nivolumab and Ipilimumab) With One Anti-cancer Targeted Drug (Cabozantinib) for Rare Genitourinary Tumors (clinicaltrials.gov) - P2 | N=224 | Recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Feb 2024 ➔ Feb 2025 | Trial primary completion date: Feb 2024 ➔ Feb 2025

Trial completion date • Trial primary completion date • Bladder Cancer • Clear Cell Renal Cell Carcinoma • Endocrine Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Kidney Medullary Carcinoma • Lung Cancer • Nasopharyngeal Carcinoma • Neuroendocrine Tumor • Oncology • Penile Cancer • Prostate Cancer • Renal Cell Carcinoma • Sarcoma • Solid Tumor • Squamous Cell Carcinoma • Testicular Cancer • Urethral Cancer • Urothelial Cancer • CD4 • PD-L1

CABINET: Testing Cabozantinib in Patients With Advanced Pancreatic Neuroendocrine and Carcinoid Tumors (clinicaltrials.gov) - P3 | N=395 | Recruiting | Sponsor: National Cancer Institute (NCI) | Suspended ➔ Recruiting

Enrollment open • Metastases • Carcinoid Tumor • Endocrine Cancer • Hepatology • Lung Cancer • Neuroendocrine Tumor • Oncology • Solid Tumor • Thymus Cancer

Adrenocortical Carcinoma Metastasis to the Thyroid: A Case Study (ENDO 2026) - "She was treated with doxorubicin, etoposide, cisplatin, and mitotane however disease progressed despite reaching mitotane therapeutic levels...Pembrolizumab was initiated but halted due to adverse events; thereafter transitioned to a clinical trial until disease progression... ACC is an uncommon malignancy with a poor prognosis. Our case presents a rare metastasis of ACC to the thyroid with disease progression despite adrenalectomy and multiple systemic therapy lines."

Case study • Clinical • Adrenal Cortex Carcinoma • Genito-urinary Cancer • Oncology • Solid Tumor • Thyroid Gland Carcinoma • Thyroid Gland Follicular Carcinoma

Testing Nivolumab and Ipilimumab Immunotherapy With or Without the Targeted Drug Cabozantinib in Recurrent, Metastatic, or Incurable Nasopharyngeal Cancer (clinicaltrials.gov) - P2 | N=50 | Suspended | Sponsor: National Cancer Institute (NCI) | Recruiting ➔ Suspended

Trial suspension • Head and Neck Cancer • Nasopharyngeal Carcinoma • Oncology • Solid Tumor • PD-L1

Testing the Addition of the Anti-cancer Drug, Cabozantinib, to the Usual Immunotherapy Treatment, Avelumab, in Patients With Metastatic Urothelial Cancer, MAIN-CAV Study (clinicaltrials.gov) - P3 | N=654 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Jun 2026 ➔ Jul 2029 | Trial primary completion date: Jun 2026 ➔ Jul 2029

Trial completion date • Trial primary completion date • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urethral Cancer • Urothelial Cancer • IFNA1

Using Nivolumab Alone or With Cabozantinib to Prevent Mucosal Melanoma Return After Surgery (clinicaltrials.gov) - P2 | N=101 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Recruiting ➔ Active, not recruiting

Enrollment closed • Melanoma • Mucosal Melanoma • Oncology • Solid Tumor • PD-L1

IMbrella B: A Study in Patients Previously Enrolled in a Genentech and/or F. Hoffmann-La Roche Ltd Sponsored Atezolizumab Study (clinicaltrials.gov) - P3 | N=1000 | Recruiting | Sponsor: Hoffmann-La Roche | Phase classification: P4 ➔ P3

Phase classification • Oncology

IMbrella B: A Study in Patients Previously Enrolled in a Genentech and/or F. Hoffmann-La Roche Ltd Sponsored Atezolizumab Study (clinicaltrials.gov) - P4 | N=1000 | Recruiting | Sponsor: Hoffmann-La Roche | Not yet recruiting ➔ Recruiting

Enrollment open • Oncology

IMbrella B: A Study in Patients Previously Enrolled in a Genentech and/or F. Hoffmann-La Roche Ltd Sponsored Atezolizumab Study (clinicaltrials.gov) - P4 | N=1000 | Not yet recruiting | Sponsor: Hoffmann-La Roche

New P4 trial • Oncology

IMbrella B: A Study in Patients Previously Enrolled in a Genentech and/or F. Hoffmann-La Roche Ltd Sponsored Atezolizumab Study (clinicaltrials.gov) - P4 | N=1000 | Recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Dec 2028 ➔ Jul 2028 | Trial primary completion date: Dec 2028 ➔ Jul 2028

Trial completion date • Trial primary completion date • Oncology