Global BulletinAll NewsFDA Approval AlertWomen in Oncology
Expert InterviewsAround the PracticeBetween the LinesFace OffFrom All AnglesMeeting of the MindsOncViewPodcastsTraining AcademyTreatment Algorithms with the Oncology BrothersVideos
Conferences
All JournalsEditorial BoardFor AuthorsYear in Review
Frontline ForumSatellite Sessions
CME/CE
Awareness MonthInteractive ToolsNurse Practitioners/Physician's AssistantsPartnersSponsoredSponsored Media
Career CenterSubscribe
Adverse Effects
Brain Cancer
Breast CancerBreast CancerBreast Cancer
Gastrointestinal CancerGastrointestinal CancerGastrointestinal CancerGastrointestinal CancerGastrointestinal CancerGastrointestinal Cancer
Genitourinary CancersGenitourinary CancersGenitourinary CancersGenitourinary Cancers
Gynecologic CancersGynecologic CancersGynecologic CancersGynecologic Cancers
Head & Neck Cancer
Hematologic OncologyHematologic OncologyHematologic OncologyHematologic Oncology
InfectionInfection
Leukemia
Lung CancerLung CancerLung Cancer
Lymphoma
Neuroendocrine Tumors
Oncology
Pediatric Cancers
Radiation Oncology
Sarcoma
Screening
Skin Cancer & Melanoma
Surgery
Thyroid Cancer
Spotlight -
  • Radiation Oncology
  • Surgery
Adverse Effects
Brain Cancer
Breast CancerBreast CancerBreast Cancer
Gastrointestinal CancerGastrointestinal CancerGastrointestinal CancerGastrointestinal CancerGastrointestinal CancerGastrointestinal Cancer
Genitourinary CancersGenitourinary CancersGenitourinary CancersGenitourinary Cancers
Gynecologic CancersGynecologic CancersGynecologic CancersGynecologic Cancers
Head & Neck Cancer
Hematologic OncologyHematologic OncologyHematologic OncologyHematologic Oncology
InfectionInfection
Leukemia
Lung CancerLung CancerLung Cancer
Lymphoma
Neuroendocrine Tumors
Oncology
Pediatric Cancers
Radiation Oncology
Sarcoma
Screening
Skin Cancer & Melanoma
Surgery
Thyroid Cancer
    • Conferences
    • CME/CE
    • Career Center
    • Subscribe
Advertisement

Recommended Dose of Pembrolizumab Plus Cabozantinib Combo Induced Response in mRCC

June 9, 2021
By Caroline Seymour
Article
Conference|ASCO Annual Meeting: Genitourinary

The recommended phase 2 dose of pembrolizumab plus cabozantinib induced a response with a manageable safety profile for patients with mRCC.

For over half of the patients with metastatic renal cell carcinoma (mRCC), the recommended phase 2 dose (RP2D) of pembrolizumab (Keytruda) plus cabozantinib (Cabometyx) induced a response with a manageable safety profile, meeting the primary end point of a phase 1/2 trial (NCT03149822), according to findings that were presented during the 2021 ASCO Annual Meeting.

Among 40 evaluable patients, the objective response rate (ORR) was 63.2% (95% CI, 0.485-1.00), which included a partial response rate of 50% (n = 3 of 6) in patients with non-clear cell RCC. The clinical benefit rate was 97.4% (95% CI, 0.88-1.00).

“Pembrolizumab and cabozantinib showed encouraging ORR in mRCC patients. Activity was seen in first- and subsequent-line settings and in clear cell RCC and non-clear cell RCC. This combination warrants further investigation,” lead study author Elizabeth R. Kessler, MD, an assistant professor of medical oncology at the University of Colorado Medicine, and co-authors wrote in the poster.

Checkpoint inhibitors and VEGF inhibitors are standard frontline treatments for patients with mRCC.

As such, the multisite, single-institution study evaluated the combination of pembrolizumab and cabozantinib in first and subsequent lines of therapy for patients with clear cell RCC and non-clear cell RCC.

The ORR at the RP2D served as the primary end point of the study.

Eligible patients had histological or cytological documentation of any histologic subtype of RCC, an ECOG performance status of 0 or 1, and measurable or evaluable disease based on RECIST version 1.1 criteria. Patients who had previously received pembrolizumab or cabozantinib were excluded, but prior treatment with other checkpoint inhibitors and VEGF inhibitors was allowed.

Patients with an active autoimmune disease on immunosuppression or who had experienced a grade 3 or greater adverse effect (AE) on prior treatment with a checkpoint inhibitor were also excluded.

Phase 1 results were presented during the 2019 Genitourinary Cancers Symposium. The present analysis included evaluable patients treated at the RP2D of 200 mg of intravenous pembrolizumab every 3 weeks plus 60 mg of oral cabozantinib daily from the phase 1 (n = 3) and phase 2 cohorts (n = 37).

Radiologic assessment was performed every 9 weeks. Treatment beyond RECIST progression in the setting of continued clinical benefit was allowed.

Baseline characteristics indicated that patients were a median age of 60.75 years. The majority of patients were male (60%) and had clear cell histology (85%), followed by non-clear cell (15%) and sarcomatoid (15%) histology. The majority of patients had prior nephrectomy (85%) and an intermediate International Metastatic RCC Database (IMDC) risk score (72.5%; poor IMDC, 12.5%).

Less than half of patients each received 0 (37.5%), 1 (40%), or at least 2 (15%) prior therapies. Prior treatment consisted of only a TKI in 43.5% of patients, immunotherapy in 42.5% of patients, and a TKI plus immunotherapy in 22.5% of patients.

Additional results indicated that the median progression-free survival was 10.4 months (95% CI, 6.3-not reached [NR]), and the median time to response was 18.1 weeks (95% CI, 17.1-NR).

Regarding safety, grade 1 or 2 treatment-related AEs (TRAEs) occurred in 98% of patients and included diarrhea (75%), dysgeusia (55%), fatigue (60%), hand-foot syndrome (33%), hypophosphatemia (48%), oral mucositis (53%), nausea/vomiting (58%), transaminitis (45%), thyroid abnormality (45%), and weight loss (63%).

Grade 3 to 5 TRAEs occurred in 47% of patients and included diarrhea (8%), fatigue (5%), hand-foot syndrome (3%), hypophosphatemia (20%), oral mucositis (5%), and transaminitis (8%).

A total of 28 patients required a dose reduction at a median of 4 cycles (range, 1-38). One grade 5 treatment-related event of reversible leukoencephalopathy syndrome occurred.

Other serious TRAEs included hypoglycemia, nephritis, pancreatitis, pneumonitis, pulmonary embolus, transaminitis, and stroke.

Reference

Kessler ER, Hu J, Srivastava G, et al. Phase I/II study of pembrolizumab and cabozantinib for metastatic renal cell carcinoma (mRCC). J Clin Oncol. 2021;39(suppl 15):4544. doi:10.1200/JCO.2021.39.15_suppl.4544

Recent Videos
A third of patients had a response [to lifileucel], and of the patients who have a response, half of them were alive at the 4-year follow-up.
We are seeing that, in those patients who have relapsed/refractory melanoma with survival measured as a few weeks and no effective treatments, about a third of these patients will have a response.
We have the current CAR [T-cell therapies], which target CD19; however, we need others.
“Every patient [with multiple myeloma] should be offered CAR T before they’re offered a bispecific, with some rare exceptions,” said Barry Paul, MD.
Barry Paul, MD, listed cilta-cel, anito-cel, and arlo-cel as 3 of the CAR T-cell therapies with the most promising efficacy in patients with multiple myeloma.
Jose Sandoval Sus, MD, discussed standard CAR T-cell therapies in patients across multiple high-risk lymphoma indications.
Elucidating nonresponses to bispecific T-cell engagers may be an important research consideration in the multiple myeloma field.
Barriers to access and financial toxicities are challenges that must be addressed for CAR T-cell therapies in LBCL, according to Jose Sandoval Sus, MD.
Fixed treatment durations with bispecific antibodies followed by observation may help in mitigating infection-related AEs, according to Shebli Atrash, MD.
Shebli Atrash, MD, stated that MRD should be considered carefully as an end point, given potential recurrence despite MRD negativity.
Related Content
Advertisement

Additional correlative data and further prospective clinical investigations are needed to inform biomarker-directed advanced RCC treatment.

Pembrolizumab Combo Exhibits Sustained Clinical Benefit in Advanced RCC

Roman Fabbricatore
August 22nd 2025
Article

Additional correlative data and further prospective clinical investigations are needed to inform biomarker-directed advanced RCC treatment.


A panel of clinical pharmacists discussed strategies for mitigating toxicities across different multiple myeloma, lymphoma, and leukemia populations.

Navigating AE Management for Cellular Therapy Across Hematologic Cancers

Tiba Al Sagheer, PharmD, BCOP, BCACP;Rebecca Gonzalez, PharmD, BCOP, FASTCT;Syeda Saba Kareem PharmD, BCOP
August 11th 2025
Podcast

A panel of clinical pharmacists discussed strategies for mitigating toxicities across different multiple myeloma, lymphoma, and leukemia populations.


Jose Sandoval Sus, MD, discussed the “revolution” that CAR T-cell therapies have facilitated for patients with large B-cell lymphomas.

Considerations for CAR T Use Across Large B-Cell Lymphoma Variants

Roman Fabbricatore
August 8th 2025
Article

Jose Sandoval Sus, MD, discussed the “revolution” that CAR T-cell therapies have facilitated for patients with large B-cell lymphomas.


Experts share their perspectives on updated clinical trial results, personalized cancer vaccine research, and other notable developments in kidney cancer.

Key Advances Across Kidney Cancer Research and Management at KCRS 2025

Thomas Powles, MBBS, MCRP, MD;David Braun, MD, PhD;Wenxin (Vincent) Xu, MD;Eric Jonasch, MD
July 28th 2025
Podcast

Experts share their perspectives on updated clinical trial results, personalized cancer vaccine research, and other notable developments in kidney cancer.


Leading experts gathered in Orlando, FL, to discuss the current and future state of cellular therapy in oncology at the 2025 ICE-T Symposium.

National ICE-T Conference Aims to Make CAR T Safer and More Available

Tim Cortese
August 2nd 2025
Article

Leading experts gathered in Orlando, Florida, to discuss the current and future state of cellular therapy in oncology at the 2025 ICE-T Symposium.


The biomarker analysis in KEYNOTE-426 showed that pembrolizumab plus axitinib therapy is associated with positive outcomes with angiogenesis in RCC.

Pembrolizumab/Axitinib Improves Survival vs Sunitinib in Advanced RCC

Tim Cortese
August 1st 2025
Article

The biomarker analysis in KEYNOTE-426 showed that pembrolizumab plus axitinib therapy is associated with positive outcomes with angiogenesis in RCC.

Related Content
Advertisement

Additional correlative data and further prospective clinical investigations are needed to inform biomarker-directed advanced RCC treatment.

Pembrolizumab Combo Exhibits Sustained Clinical Benefit in Advanced RCC

Roman Fabbricatore
August 22nd 2025
Article

Additional correlative data and further prospective clinical investigations are needed to inform biomarker-directed advanced RCC treatment.


A panel of clinical pharmacists discussed strategies for mitigating toxicities across different multiple myeloma, lymphoma, and leukemia populations.

Navigating AE Management for Cellular Therapy Across Hematologic Cancers

Tiba Al Sagheer, PharmD, BCOP, BCACP;Rebecca Gonzalez, PharmD, BCOP, FASTCT;Syeda Saba Kareem PharmD, BCOP
August 11th 2025
Podcast

A panel of clinical pharmacists discussed strategies for mitigating toxicities across different multiple myeloma, lymphoma, and leukemia populations.


Jose Sandoval Sus, MD, discussed the “revolution” that CAR T-cell therapies have facilitated for patients with large B-cell lymphomas.

Considerations for CAR T Use Across Large B-Cell Lymphoma Variants

Roman Fabbricatore
August 8th 2025
Article

Jose Sandoval Sus, MD, discussed the “revolution” that CAR T-cell therapies have facilitated for patients with large B-cell lymphomas.


Experts share their perspectives on updated clinical trial results, personalized cancer vaccine research, and other notable developments in kidney cancer.

Key Advances Across Kidney Cancer Research and Management at KCRS 2025

Thomas Powles, MBBS, MCRP, MD;David Braun, MD, PhD;Wenxin (Vincent) Xu, MD;Eric Jonasch, MD
July 28th 2025
Podcast

Experts share their perspectives on updated clinical trial results, personalized cancer vaccine research, and other notable developments in kidney cancer.


Leading experts gathered in Orlando, FL, to discuss the current and future state of cellular therapy in oncology at the 2025 ICE-T Symposium.

National ICE-T Conference Aims to Make CAR T Safer and More Available

Tim Cortese
August 2nd 2025
Article

Leading experts gathered in Orlando, Florida, to discuss the current and future state of cellular therapy in oncology at the 2025 ICE-T Symposium.


The biomarker analysis in KEYNOTE-426 showed that pembrolizumab plus axitinib therapy is associated with positive outcomes with angiogenesis in RCC.

Pembrolizumab/Axitinib Improves Survival vs Sunitinib in Advanced RCC

Tim Cortese
August 1st 2025
Article

The biomarker analysis in KEYNOTE-426 showed that pembrolizumab plus axitinib therapy is associated with positive outcomes with angiogenesis in RCC.

Advertisement
About
Advertise
CureToday.com
OncLive.com
OncNursingNews.com
TargetedOnc.com
Editorial
Contact
Terms and Conditions
Privacy
Do Not Sell My Personal Information
Contact Info

2 Commerce Drive
Cranbury, NJ 08512

609-716-7777

© 2025 MJH Life Sciences

All rights reserved.