imdatifan (NKT2152) / NiKang Therap, Jiangsu Hansoh Pharma - LARVOL DELTA

A Study Evaluating the Efficacy and Safety of Multiple Immunotherapy-Based Treatment Combinations in Patients With Advanced Liver Cancers (Morpheus-Liver) (clinicaltrials.gov) - P1/2 | N=518 | Recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Dec 2026 ➔ Dec 2027 | Trial primary completion date: Dec 2026 ➔ Dec 2027

Trial completion date • Trial primary completion date • Liver Cancer • Oncology • Solid Tumor • PD-L1

Targeting HIF-2α in renal cell carcinoma: Expanding upon belzutifan. (PubMed, Cancer) - "By expanding upon the foundation established by belzutifan, the field is poised for further therapeutic advances."

First-in-human • Journal • Review • Clear Cell Renal Cell Carcinoma • Developmental Disorders • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Von Hippel-Lindau Syndrome • EPAS1 • VHL

Phase Ib/II Clinical Study of SHR-8068 Combined With Adebrelimab and Other Anti-tumor Drugs in the Treatment of Advanced Renal Cell Carcinom (clinicaltrials.gov) - P1/2 | N=139 | Recruiting | Sponsor: Suzhou Suncadia Biopharmaceuticals Co., Ltd. | Not yet recruiting ➔ Recruiting

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

HIF2A as a prognostic and clinical therapeutic target in ovarian clear cell carcinoma. (PubMed, Int J Cancer) - "Moreover, treatment with NKT2152 significantly reduced tumor growth in both cell line-derived and patient-derived xenograft models. In conclusion, our findings provide novel insights into the prognostic and functional role of HIF2A in ovarian CCC and underscore its potential as a promising therapeutic target."

Journal • Clear Cell Carcinoma • Endometriosis • Gynecology • Oncology • Ovarian Cancer • Solid Tumor • Women's Health • EPAS1

A PHASE 1/2, OPEN LABEL DOSE-ESCALATION AND EXPANSION TRIAL OF NKT2152, AN ORALLY ADMINISTERED HIF2α INHIBITOR, TO INVESTIGATE SAFETY, PK, PD AND CLINICAL ACTIVITY IN PATIENTS WITH ADVANCED ccRCC (KCRS 2023) - "Adults who have advanced ccRCC without available standard therapy), ECOG PS 0-2, with measurable disease per RECIST 1.1 are eligible. Patients who have had prior HIF2a inhibitors, require supplemental oxygen, and with significant cardiac disease are excluded. Tumor assessments by CT or MRI are conducted every 8 weeks until 48 weeks, then every 12 weeks thereafter. Adverse events will be monitored and graded in severity using CTCAE v5.0. The Phase 1 study is currently actively accruing in the United States with Phase 2 dose expansion anticipated to start in Q3, 2023."

Clinical • Metastases • P1/2 data • Clear Cell Renal Cell Carcinoma

NKT2152, a novel oral HIF-2α inhibitor, in participants (pts) with previously treated advanced clear cell renal carcinoma (accRCC): Preliminary results of a phase I/II study (ESMO 2024) - P1/2 | "NKT2152 demonstrated robust anti-tumor activity in heavily pretreated accRCC pts. The safety profile was consistent with this class of agent."

Clinical • Metastases • P1/2 data • Clear Cell Renal Cell Carcinoma • Kidney Cancer • Oncology • Solid Tumor • EPAS1

Phase Ib/II Clinical Study of SHR-8068 Combined With Adebrelimab and Other Anti-tumor Drugs in the Treatment of Advanced Renal Cell Carcinom (clinicaltrials.gov) - P1/2 | N=139 | Not yet recruiting | Sponsor: Suzhou Suncadia Biopharmaceuticals Co., Ltd.

New P1/2 trial • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Targeting of HIF2-driven cachexia in kidney cancer. (PubMed, Nat Med) - "Consistent with these observations, two different allosteric HIF2 inhibitors, belzutifan and NKT2152, rapidly ameliorated hypercalcemia and cachexia in patients with ccRCC, including in some who did not exhibit objective tumor shrinkage. Our findings support prospective clinical studies to determine whether HIF2 inhibitors can be leveraged not only for tumor control, but also for the treatment of cancer-associated cachexia in renal cell carcinoma."

Journal • Cachexia • Clear Cell Renal Cell Carcinoma • Endocrine Disorders • Genito-urinary Cancer • Kidney Cancer • Metabolic Disorders • Oncology • Renal Cell Carcinoma • Solid Tumor • PTHLH

NKT2152-202: Ph2 Study NKT2152 With Palbociclib & Sasanlimab in Subjects With Advanced Clear Cell Renal Cell Carcinoma (ccRcc) (clinicaltrials.gov) - P2 | N=18 | Terminated | Sponsor: NiKang Therapeutics, Inc. | N=172 ➔ 18 | Trial completion date: Jun 2026 ➔ Sep 2025 | Active, not recruiting ➔ Terminated; This study was terminated as a result of Sponsor portfolio reprioritization.

Enrollment change • Trial completion date • Trial termination • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Kidney Cancer • Nephrology • Oncology • Renal Cell Carcinoma • Renal Disease • Solid Tumor • Urethral Cancer • Urology

NKT2152-101: A Study of NKT2152, a HIF2α Inhibitor, in Patients With Advanced Clear Cell Renal Cell Carcinoma (clinicaltrials.gov) - P1/2 | N=120 | Terminated | Sponsor: NiKang Therapeutics, Inc. | Trial completion date: Sep 2026 ➔ Sep 2025 | Active, not recruiting ➔ Terminated | Trial primary completion date: May 2025 ➔ Aug 2025; This study was terminated as a result of Sponsor portfolio reprioritization.

Trial completion date • Trial primary completion date • Trial termination • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • PD-L1

Baseline levels of HIF2 target proteins and response to the HIF2α inhibitor NKT2152 in patients with metastatic clear cell renal cell carcinoma (AACR-NCI-EORTC 2025) - P1/2 | "In preclinical models, VHL truncating mutations (causing complete loss of function) are known to lead to the highest HIF levels. As such, the observation that low expression of GLUT1 is inversely associated with VHL truncating mutations further supports GLUT1 expression as a surrogate marker of VHL/HIF2 pathway activation."

Clinical • Metastases • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Solid Tumor • CCND1 • SLC2A1 • VHL

HIF2-driven PTHrP Causes Cachexia and Hypercalcemia in Kidney Cancer: Treatment with HIF2 Inhibitors. (PubMed, bioRxiv) - "Further, we show that the increased PTHLH expression is both necessary and sufficient for the induction of hypercalcemia and cachexia in preclinical orthotopic cell line tumor models. Consistent with these observations, two different allosteric HIF2 inhibitors, belzutifan and NKT2152, rapidly ameliorated hypercalcemia and cachexia in ccRCC patients, including in some patients who did not exhibit objective tumor shrinkage."

Journal • Cachexia • Clear Cell Renal Cell Carcinoma • Endocrine Disorders • Genito-urinary Cancer • Kidney Cancer • Metabolic Disorders • Oncology • Renal Cell Carcinoma • Solid Tumor • PTHLH

Study of HS-10516 Combination Therapy in Patients With Advanced Renal Cell Carcinoma (clinicaltrials.gov) - P1/2 | N=104 | Recruiting | Sponsor: Jiangsu Hansoh Pharmaceutical Co., Ltd.

New P1/2 trial • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Hypoxia Inducible Factor-2α (HIF-2α) Pathway Inhibitors. (PubMed, J Kidney Cancer VHL) - "We discuss the major key inhibitors, with focus on belzutifan and review the various trials investigating its efficacy in monotherapy as well as in combination therapies in RCC...We also highlight emerging HIF-2α inhibitors currently in clinical trials, namely casdatifan, NKT-2152, and DFF332. Finally, we address the major toxicities and management of these inhibitors."

Journal • Review • Endocrine Cancer • Genito-urinary Cancer • Neuroendocrine Tumor • Oncology • Pancreatic Cancer • Renal Cell Carcinoma • Solid Tumor • Von Hippel-Lindau Syndrome • ARNT • CA9 • EPAS1 • POU5F1 • VHL

NKT2152 Ushers in a New Era of HIF-2α Inhibition in Pretreated Advanced ccRCC (OncLive) - "The novel HIF-2α inhibitor NKT2152 has demonstrated promising antitumor activity and a tolerable safety profile in patients with advanced clear cell renal cell carcinoma (ccRCC) that may prompt changes to the treatment paradigm in the future, according to Toni Choueiri, MD."

Video • Renal Cell Carcinoma

Dr Choueiri on the Significance of Targeting HIF-2α With NKT2152 in ccRCC (OncLive) - "On-target toxicities associated with NKT2152 include hypoxia, anemia, and fatigue, Choueiri notes. Anemia arises due to decreased erythropoietin levels, a known effect of HIF-2α inhibition, he adds. A distinguishing feature of NKT2152 is its extended half-life, measured at a median of 38 days in this trial, which sets this agent apart from other HIF-2α inhibitors, such as belzutifan (Welireg), Choueiri says. These preliminary findings support the further investigation of NKT2152 in advanced ccRCC, he concludes."

Video • Renal Cell Carcinoma

NiKang Therapeutics Announces First Patient Dosed in a Phase 1b/2 Study of NKT2152 in Combination with Standard-of-Care in First-Line Regimen for Hepatocellular Carcinoma (Businesswire) - "NiKang Therapeutics...today announced that the first patient has been dosed in the global randomized phase 1b/2 clinical study evaluating NKT2152, a highly potent, selective and orally bioavailable small molecule HIF2α inhibitor, in combination with standard-of-care regimen of atezolizumab (Tecentriq) and bevacizumab (Avastin) in the first-line treatment of patients with advanced or metastatic HCC. This study is being conducted under a clinical trial collaboration with F. Hoffmann-La Roche Ltd ('Roche') as part of Roche’s MORPHEUS-liver platform trial (NCT04524871)....'NKT2152 has demonstrated significant anti-tumor efficacy and a favorable safety profile not only in human ccRCC patients but also in preclinical xenograft models of solid tumors beyond ccRCC, underscoring its potential for broad application in human cancer treatments.'"

Preclinical • Trial status • Clear Cell Renal Cell Carcinoma • Hepatocellular Cancer • Von Hippel-Lindau Syndrome

A Study Evaluating the Efficacy and Safety of Multiple Immunotherapy-Based Treatment Combinations in Patients With Advanced Liver Cancers (Morpheus-Liver) (clinicaltrials.gov) - P1/2 | N=518 | Recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Aug 2026 ➔ Dec 2026 | Trial primary completion date: Aug 2026 ➔ Dec 2026

Metastases • Trial completion date • Trial primary completion date • Hepatocellular Cancer • Hepatology • Liver Cancer • Oncology • Solid Tumor • PD-L1

NKT2152-202: Ph2 Study NKT2152 with Palbociclib & Sasanlimab in Subjects with Advanced Clear Cell Renal Cell Carcinoma (ccRcc) (clinicaltrials.gov) - P2 | N=172 | Active, not recruiting | Sponsor: NiKang Therapeutics, Inc. | Recruiting ➔ Active, not recruiting | Trial completion date: Sep 2026 ➔ Jun 2026 | Trial primary completion date: Jun 2026 ➔ Jun 2025

Combination therapy • Enrollment closed • Metastases • Trial completion date • Trial primary completion date • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Kidney Cancer • Nephrology • Oncology • Renal Cell Carcinoma • Renal Disease • Solid Tumor • Urethral Cancer • Urology

NKT2152-101: A Study of NKT2152, a HIF2α Inhibitor, in Patients with Advanced Clear Cell Renal Cell Carcinoma (clinicaltrials.gov) - P1/2 | N=128 | Active, not recruiting | Sponsor: NiKang Therapeutics, Inc. | Recruiting ➔ Active, not recruiting | Trial primary completion date: Sep 2024 ➔ May 2025

Enrollment closed • Metastases • Trial primary completion date • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • PD-L1

Dr Choueiri on Initial Efficacy Data With NKT2152 in Pretreated ccRCC (OncLive) - "Toni K. Choueiri, MD, discusses early findings from a phase 1/2 trial evaluating NKT2152 in previously-treated advanced clear cell renal cell carcinoma."

Video • Renal Cell Carcinoma

NKT2152 an oral hf2 inhibitor with half life of 38 days has activity in heavily treated ccRCC with ORR 20% (26% with longer followup) with no unexpected toxicity. Trials ongoing exploring dose and activity following belzutifan - open @DanaFarber_GU @DrChoueiri

Dr Jonasch on the Preliminary Efficacy of NKT-2152 in Advanced ccRCC (OncLive) - "Eric Jonasch, MD, discusses preliminary findings from a trial investigating NKT-2152 in previously treated advanced clear cell renal cell carcinoma."

Video • Renal Cell Carcinoma

Episode 344: ESMO 2024 - NKT2152, a HIF inhibitor in RCC - "Brad McGregor joins Brian and Tom to discuss a new HIF inhibitor, NKT2152, and preliminary data in RCC."

Audio • Renal Cell Carcinoma

NiKang Therapeutics to Present Preliminary Results of Phase 1/2 Clinical Trial of NKT2152 in Patients with Previously Treated Advanced Clear Cell Renal Cell Carcinoma at ESMO 2024 Congress (Businesswire) - "NiKang Therapeutics Inc...announced that preliminary data from its ongoing Phase 1/2 clinical trial evaluating NKT2152 for the treatment of previously treated advanced clear cell renal cell carcinoma (ccRCC) will be presented in an oral presentation at the European Society for Medical Oncology (ESMO) 2024 Congress on September 13, 2024, in Barcelona, Spain."

P1/2 data • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Von Hippel-Lindau Syndrome