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RCCApril 2026
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Renal Cell Carcinoma — Monthly Compass
Apr 01–30, 2026 • Priority Updates • 3–5 minute read
 
A curated, practice-minded digest of what moved in renal cell carcinoma this month — regulatory signals, clinical development, and the most practice-relevant publications.
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renal cell carcinoma updates
Key Highlights
Key Highlights
  • Key Clinical Development Updates
    • FDA accepted for priority review supplemental applications for WELIREG (belzutifan) combined with KEYTRUDA or KEYTRUDA QLEX as adjuvant therapy for certain RCC, assigning a PDUFA target action date of June 19, 2026.
    • FDA accepted two sNDAs for WELIREG plus LENVIMA in previously treated advanced RCC with a PDUFA date of October 4, 2026, alongside an April 21 update on the Phase 3 LITESPARK‑012 first‑line clear cell RCC program.
  • Important Clinical Trial Publications
    • In the randomized phase 2 TACITO trial, adding healthy donor fecal microbiota transplantation to first‑line pembrolizumab plus axitinib significantly prolonged median progression‑free survival versus placebo FMT in metastatic RCC, with specific bacterial strain acquisition or loss correlating with improved outcomes.
    • Final results from CALYPSO demonstrated clinically meaningful overall survival with savolitinib plus durvalumab in metastatic papillary RCC, with exploratory analyses indicating circulating tumor DNA clearance and variant allele frequency reduction as potential predictive biomarkers.
  • Key Conference Updates
    • AACR/IKCS 2026 highlighted deeper HIF‑axis targeting via the first‑in‑human ARNT degrader NEO‑811 and advancement of CAIX‑targeted TLX250‑Tx into the pivotal LUTEON trial, while darlifarnib (KO‑2806) plus cabozantinib achieved 44% ORR and 94% DCR in cabozantinib‑pretreated clear cell RCC supporting a resistance‑modifying strategy.
  • Emerging Themes & Macro-Trends
    • Radiopharmaceutical expansion is catalyzing dosimetry‑guided regulatory pathways, and perioperative IO plus inflammation blockade could shift endpoint emphasis toward MPR/pCR/EFS.
    • Strategic priorities emphasize advancing HIF‑axis degraders and CAIX radiotherapeutics, designing resistance‑focused combinations after VEGFR‑TKI exposure, and integrating microbiome and inflammatory‑axis tools into perioperative RCC programs.
FDA Approvals/Withdrawals
FDA Approvals/Withdrawals
  • There are no press releases between 2026-04-01 and 2026-04-30 about renal cell carcinoma.
Clinical Development Regulatory Updates
Clinical Development Regulatory Updates
  • Merck and Eisai provided an April 21 update on the Phase 3 LITESPARK-012 trial in first-line advanced clear cell RCC and reiterated that FDA has accepted two sNDAs for WELIREG (belzutifan) plus LENVIMA (lenvatinib) in certain previously treated advanced RCC, assigning a PDUFA target action date of October 4, 2026. The release underscores ongoing FDA review timelines alongside clinical readouts in RCC. (merck.com) ¹ (read more)
  • In its April 30 Q1 2026 update, Merck reported that the FDA accepted for priority review supplemental applications for WELIREG combined with KEYTRUDA or KEYTRUDA QLEX for adjuvant treatment of certain RCC, with a PDUFA date of June 19, 2026. The company also noted FDA acceptance of sNDAs for WELIREG plus LENVIMA in previously treated advanced RCC, with a PDUFA date of October 4, 2026. (merck.com) ² (read more)
Conference
Major Conference Updates
Conference Information
  • AACR Annual Meeting 2026; San Diego Convention Center, San Diego, California; April 17–22, 2026. (read more)
  • International Kidney Cancer Symposium (IKCS): Europe 2026; Paris, France; April 15–17, 2026. (read more)
  • Overall sentiment: RCC presentations emphasized HIF‑axis reinvention (beyond HIF‑2α), resistance‑modifying combinations, radiotheranostics targeting CAIX, and early‑setting immune‑microenvironment modulation—signaling a pivot from “more IO/TKI” to biology‑driven precision add‑ons. (read more)
  • Theme 1: HIF Pathway Reinvented via Targeted Protein Degradation
    • Significance: Moving past HIF‑2α inhibition toward ARNT (HIF‑1β) degradation promises deeper pathway shutdown and potential activity in belzutifan‑resistant ccRCC. (read more)
    • Mechanism insights / clinical impact: NEO‑811, a molecular glue degrader of ARNT, was featured in AACR’s New Drugs on the Horizon and is being evaluated in a first‑in‑human Phase 1/2 in ccRCC; degrading HIF’s obligate partner could suppress hypoxia‑driven transcription more comprehensively than HIF‑2α blockade. (read more)
    • Patient populations affected: Locally advanced or metastatic clear cell RCC, including post‑IO/TKI settings where HIF‑axis escape drives progression. (read more)
  • Theme 2: Resistance‑Overcoming Combinations with Farnesyl Transferase Inhibition
    • Significance: Combining darlifarnib (KO‑2806) with cabozantinib seeks to resensitize VEGFR‑TKI–experienced tumors, a major gap after cabozantinib failure. (read more)
    • Mechanism insights / clinical impact: By inhibiting farnesylation of RHEB to suppress mTORC1, darlifarnib plus cabozantinib achieved 44% ORR and 94% DCR in cabozantinib‑pretreated ccRCC (FIT‑001), with durable responses and manageable safety—supporting a resistance‑modifying role. (read more)
    • Patient populations affected: Heavily pretreated advanced ccRCC, specifically cabozantinib‑pretreated and post‑IO cohorts, across IKCS‑Europe sites. (read more)
  • Theme 3: CAIX‑Targeted Radiotheranostics Advance Toward Pivotal Testing
    • Significance: Radiopharmaceuticals offer tumor‑selective cytotoxicity independent of prior IO/TKI sequencing and may benefit heterogeneous, late‑line ccRCC. (read more)
    • Mechanism insights / clinical impact: TLX250‑Tx (lutetium (177Lu) girentuximab tetraxetan) progressed into Part 1 of LUTEON, a pivotal trial as monotherapy in advanced ccRCC—positioning CAIX RLT as a potential new pillar. (read more)
    • Patient populations affected: Advanced or metastatic ccRCC expressing CAIX, including IO/TKI‑refractory disease where targeted beta‑emission may be advantageous. (read more)
  • Theme 4: Early‑Setting and Microbiome‑Informed Immune Modulation
    • Significance: Perioperative and microbiome strategies aim to raise cure rates and extend IO responsiveness. (read more)
    • Mechanism insights / clinical impact: SPARC‑1 tested neoadjuvant canakinumab (IL‑1β blockade) + spartalizumab (PD‑1) in localized ccRCC with favorable tolerability and encouraging activity; IKCS spotlighted extended follow‑up of TACITO (FMT + pembrolizumab + axitinib) and dysbiosis analyses, underscoring immune‑microbiome leverage. (read more)
    • Patient populations affected: Localized resectable ccRCC (neoadjuvant) and metastatic RCC exploring microbiome‑augmented IO/TKI combinations. (read more)
  • Significance
    • Expected clinical or translational readouts: FIT‑001 Phase 1b expansion updates; NEO‑811 ongoing Phase 1/2; LUTEON enrollment milestones. (read more)
    • Regulatory or policy implications: Radiopharma growth may accelerate dosimetry‑guided pathways; early‑setting IO+inflammation blockade could influence endpoint selection (MPR/pCR/EFS). (read more)
    • Potential shifts in standard of care: If validated, darlifarnib+cabozantinib could redefine post‑cabo sequencing; ARNT degradation may create an option in HIF‑2α–exposed/resistant disease; CAIX RLT could emerge as a new late‑line standard. (read more)
    • Strategic implications: Prioritize HIF‑axis degraders and CAIX radiotherapeutics; design resistance‑focused combo trials after VEGFR‑TKI; incorporate microbiome and inflammatory‑axis tools in perioperative RCC programs. (read more)
Publications Related to Approved Drugs
Unknown Drug
There are no new publication updates during the 2026-04-01 to 2026-04-30 for renal cell carcinoma.
New Publications Related to Drugs in Clinical Trial Development
Phase 2
Metastasis-directed Therapy With or Without Pembrolizumab for Oligometastatic Clear Cell Renal Cell Carcinoma: Pooled Analysis of Two Prospective Single-arm Phase 2 Trials. A pooled analysis of two phase 2 trials suggests that adding maintenance pembrolizumab to radiotherapy-based metastasis-directed therapy (MDT) improves progression-free survival compared to MDT alone in patients with oligometastatic clear cell renal cell carcinoma. The combination therapy also induced favorable immunomodulatory changes, including the systemic induction of activated CD8+ T cells, supporting the rationale for the ongoing randomized ASTROs trial. ()
Phase 2
Elraglusib and chemotherapy in metastatic pancreatic ductal adenocarcinoma: a randomized controlled phase 2 trial. The addition of the GSK-3β inhibitor elraglusib to gemcitabine and nab-paclitaxel significantly improved median overall survival and 1-year survival rates in patients with previously untreated metastatic pancreatic ductal adenocarcinoma. These findings support the clinical activity of this combination as a first-line treatment and provide a biological rationale for advancing to phase 3 trials. ()
Phase 2
Phase II Trial of Ixazomib Combined with Gemcitabine and Doxorubicin in Patients with SMARCB1-Deficient Renal Medullary Carcinoma. In a phase II trial for SMARCB1-deficient renal medullary carcinoma, the addition of the proteasome inhibitor ixazomib to gemcitabine and doxorubicin modestly increased the objective response rate but failed to extend the 28-week disease-control rate, crossing the predefined futility boundary. Multi-omic correlative analyses revealed that immune-inflamed tumors correlated with response, while stromal-myeloid niches and specific plastic epithelial states were associated with resistance, providing critical insights for future mechanism-directed trials. ()
Phase 1
Fecal microbiota transplantation plus immunotherapy in metastatic renal cell carcinoma: the phase 1 PERFORM trial. The phase 1 PERFORM trial demonstrated that healthy donor fecal microbiota transplantation (FMT) combined with first-line immune checkpoint inhibitors is safe and yields a 50% objective response rate in patients with metastatic renal cell carcinoma. Durable engraftment of anti-inflammatory taxa correlated with reduced toxicity and improved response, highlighting the potential of functional microbiome modulation to optimize immunotherapy outcomes. ()
Phase 3
CALYPSO: Final Results of Savolitinib and Durvalumab Combination in Metastatic Papillary Renal Cancer. Final results from the CALYPSO study confirm that the combination of the MET inhibitor savolitinib and the anti-PD-L1 antibody durvalumab provides clinically meaningful overall survival benefits, particularly in patients with MET-driven metastatic papillary renal cancer. Furthermore, exploratory analyses suggest that circulating tumor DNA clearance and variant allele frequency reduction may serve as useful predictive biomarkers for treatment response. ()
Phase 2
Cabozantinib in patients with non-locally pretreated brain metastases from renal cell carcinoma: Results of the multicenter phase II trial CABRAMET. The phase II CABRAMET trial demonstrated that cabozantinib exhibits significant and prolonged efficacy in patients with non-locally pretreated brain metastases from renal cell carcinoma, achieving a 61.5% objective response rate in the brain. This study highlights cabozantinib as a highly active and tolerable systemic treatment option for this challenging patient population, particularly in the first-line setting. ()
Phase 2
KIM-1 in Advanced Papillary and Clear Cell Renal Cell Carcinoma. An exploratory analysis from the CALYPSO trial revealed that Kidney Injury Molecule-1 (KIM-1) levels are significantly higher in advanced papillary renal cell carcinoma (pRCC) compared to clear cell RCC (ccRCC) and decrease with systemic therapy in both subtypes. In ccRCC, high baseline KIM-1 and on-treatment increases were associated with worse survival outcomes, supporting its potential utility as a prognostic and predictive biomarker in advanced disease. ()
PHASE1, PHASE2
Fecal microbiota transplantation plus pembrolizumab and axitinib in metastatic renal cell carcinoma: the randomized phase 2 TACITO trial. In the randomized phase 2 TACITO trial, the addition of healthy donor fecal microbiota transplantation (FMT) to first-line pembrolizumab and axitinib significantly prolonged median progression-free survival compared to placebo FMT in patients with metastatic renal cell carcinoma. Microbiome analysis indicated that the acquisition or loss of specific bacterial strains, rather than total engraftment, was associated with improved clinical outcomes, supporting the potential efficacy of selected donor FMT to enhance immunotherapy. ()
Clinical Trials
Clinical Trials Summary
Number of Clinical Trials in renal cell carcinoma updated from 2026-04-01 to 2026-04-30:
Phase 1Phase 1/2Phase 2Phase 2/3Phase 3Phase 4Total
Enrolling by Invitation-------
Not Yet Recruiting1-2---3
Recruiting211012-3-46
Available-------
Approved for Marketing-------
Active, Not Recruiting13314-1-31
Completed-------
Total351328-4-80
Phase 1 Clinical Trials within 3 Months of Primary Completion Date:
DRUGNCTIDStatusClinical Trial NameCompletion Date
: Nivolumab, : Ipilimumab, Myrciaria dubia Prebiotic Supplement NCT06049576 ACTIVE_NOT_RECRUITING Combination Nivolumab and Ipilimumab With and Without Camu Camu in First Line Treatment of Metastatic Renal Cell Carcinoma 2026-06-23
Phase 2 Clinical Trials within 3 Months of Primary Completion Date:
DRUGNCTIDStatusClinical Trial NameCompletion Date
Irinotecan, Gemcitabine - 28 day cycle, Lomustine, 9-ING-41, Carboplatin., Paclitaxel., Doxorubicin., Gemcitabine - 21 day cycle, Nab paclitaxel. NCT03678883 ACTIVE_NOT_RECRUITING Phase 1/2 Study of 9-ING-41, a Glycogen Synthase Kinase-3 Beta (GSK-3β) Inhibitor, as a Single Agent and Combined With Chemotherapy, in Patients With Refractory Hematologic Malignancies or Solid Tumors 2026-06
Cabozantinib, Cabozantinib S-malate NCT02867592 ACTIVE_NOT_RECRUITING Phase 2 Trial of XL184 (Cabozantinib) an Oral Small-Molecule Inhibitor of Multiple Kinases, in Children and Young Adults With Refractory Sarcomas, Wilms Tumor, and Other Rare Tumors 2026-06-27
Phase 3 Clinical Trials within 3 Months of Primary Completion Date:
No phase 3 trials completing within the next three months.
Phase 4 Clinical Trials within 3 Months of Primary Completion Date:
No phase 4 trials completing within the next three months.
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