KIN-3248 / Xoma - LARVOL DELTA

A Study to Evaluate KIN-3248 in Participants With Advanced Tumors Harboring FGFR2 and//or FGFR3 Gene Alterations (clinicaltrials.gov) - P1 | N=54 | Terminated | Sponsor: Kinnate Biopharma | Trial completion date: Sep 2026 ➔ Oct 2024 | Active, not recruiting ➔ Terminated | Trial primary completion date: Jun 2026 ➔ Oct 2024; Due to a change in the Sponsor's corporate strategy the study was terminated early by the Sponsor prior to enrollment into the dose expansion part of the study (Part B).

Trial completion date • Trial primary completion date • Trial termination • Biliary Cancer • Cholangiocarcinoma • Oncology • Solid Tumor • Urothelial Cancer • FGFR2

A Phase 1 Study of KIN-3248, an irreversible small molecule pan-FGFR inhibitor, in Patients with Advanced FGFR 2/3 Driven Solid Tumors. (PubMed, Cancer Res Commun) - P1 | "The trial was terminated early for commercial considerations; therefore, RP2D was not established. Preliminary clinical data suggest that KIN-3248 is a safe, oral FGFR1-4 inhibitor with favorable PK parameters, though further dose escalation was required to nominate the MTD/RP2D."

Journal • Metastases • P1 data • Biliary Cancer • Cholangiocarcinoma • Dental Disorders • Gastrointestinal Cancer • Immunology • Metabolic Disorders • Nephrology • Oncology • Renal Disease • Solid Tumor • Stomatitis • FGFR2 • FGFR3

A Phase 1 Study of KIN-3248, an irreversible small molecule pan-FGFR inhibitor, in Patients with Advanced FGFR 2/3 Driven Solid Tumors (Cancer Res Commun) - P1/1b | N=54 | NCT05242822 | "Fifty-four patients received doses ranging from 5mg to 50mg orally daily across 6 cohorts. Intrahepatic cholangiocarcinoma (48.1%), gastric (9.3%) and urothelial (7.4%) were the most common tumors. Tumors harbored FGFR2 (68.5%) or FGFR3 (31.5%) alterations—23 (42.6%) received prior FGFR inhibitors....Five partial responses were observed; 4 in FGFR inhibitor naïve and 1 in FGFR pretreated patients. Pretreatment ctDNA profiling confirmed FGFR2/3 alterations in 63.3% of cases and clearance at Cycle 2 associated with radiographic response."

P1 data • Cholangiocarcinoma • Gastric Cancer • Urothelial Cancer

The irreversible FGFR inhibitor KIN-3248 overcomes FGFR2 kinase domain mutations. (PubMed, Clin Cancer Res) - "Thus, KIN-3248 is a novel FGFR1-4 inhibitor whose distinct activity profile against FGFR kinase domain mutations highlights its potential for the treatment of ICC and other FGFR-driven cancers."

Journal • Biliary Cancer • Bladder Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • FGFR2 • FGFR3

Discovery of KIN-3248, An Irreversible, Next Generation FGFR Inhibitor for the Treatment of Advanced Tumors Harboring FGFR2 and/or FGFR3 Gene Alterations. (PubMed, J Med Chem) - "Herein, we describe how structure-based drug design (SBDD) was used to enable the discovery of the potent and kinome selective pan-FGFR inhibitor KIN-3248, which is active against many acquired resistance mutations. KIN-3248 is currently in phase I clinical development for the treatment of advanced tumors harboring FGFR2 and/or FGFR3 gene alterations."

Journal • Metastases • Oncology • FGFR2 • FGFR3

A Study to Evaluate KIN-3248 in Participants With Advanced Tumors Harboring FGFR2 and//or FGFR3 Gene Alterations (clinicaltrials.gov) - P1 | N=54 | Active, not recruiting | Sponsor: Kinnate Biopharma | Recruiting ➔ Active, not recruiting | N=120 ➔ 54

Enrollment change • Enrollment closed • Metastases • Biliary Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor • Urothelial Cancer • FGFR2

Phase I study evaluating KIN-3248, a next-generation, irreversible pan-FGFR inhibitor, in patients with advanced cholangiocarcinoma, urothelial carcinoma and other solid tumors harboring FGFR2 and/or FGFR3 gene alterations (ESMO 2023) - P1 | "Secondary objectives include pharmacokinetic and pharmacodynamic assessments including measures of FGFR pathway modulation. Planned sample size is 140 pts and the study is enrolling patients in the US, EU and globally."

Clinical • Metastases • P1 data • Biliary Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor • Urothelial Cancer • FGFR2 • FGFR3

Kinnate Biopharma Inc. Announces Pipeline Updates, Strategic Reprioritization and Workforce Restructuring (GlobeNewswire) - P1/1b | N=120 | NCT05242822 | Sponsor: Kinnate Biopharma | "As of September 11, 2023, the data cutoff, a total of 54 patients were enrolled in the ongoing dose escalation trial for KIN-3248, spanning 6 different dose levels....The predicted efficacious dose of 40 mg QD (DL 5) has been cleared, and further exploration is ongoing at the 50 mg QD dose (DL 6). Two PRs were observed, with 1 confirmed PR in a patient with pancreatic cancer who had not received prior treatment with an FGFR2 inhibitor; treatment began at 20 mg QD and was then increased to 30 mg QD....As of the data cut off, the maximum tolerated dose has not yet been determined. The safety and tolerability profile of KIN-3248 is consistent with other FGFR inhibitors in clinical development or currently approved."

P1 data • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor

Kinnate Biopharma Inc. Reports Second Quarter 2023 Financial Results and Recent Corporate Updates (GlobeNewswire) - "First presentation on the structure and discovery of FGFR inhibitor, KIN-3248, upcoming at the 2023 American Chemical Society on August 16."

Preclinical • Oncology

Phase 1/1b study evaluating KIN-3248, a next-generation, irreversible pan-FGFR inhibitor (FGFRi), in patients (pts) with advanced cholangiocarcinoma (CCA) and other solid tumors harboring FGFR2 and/or FGFR3 gene alterations (ESMO-GI 2023) - P1 | "Reversible FGFRi are approved for the treatment of pts with locally advanced or metastatic CCA harboring FGFR2 gene fusions or rearrangements (pemigatinib and infigratinib) or metastatic urothelial carcinoma (UC) with susceptible FGFR2 or FGFR3 genetic alterations (erdafitinib). Secondary objectives include pharmacokinetic and pharmacodynamic assessments including measures of FGFR pathway modulation. The study is actively enrolling patients in the US and globally.Clinical trial identification: NCT05242822.Legal entity responsible for the study: Kinnate Biopharma."

Clinical • Metastases • P1 data • Biliary Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor • FGFR2 • FGFR3

Discovery of KIN-3248, an irreversible, next generation FGFR inhibitor (ACS-Fall 2023) - "KIN-3248 is active against acquired gatekeeper resistance mutations FGFR2V565F and FGFR3V555M along with the molecular brake alterations FGFR2N550K and FGFR3N540K as well as the activating mutation FGFR3K650M. KIN-3248 is currently in phase I clinical development for the treatment of advanced tumors harboring FGFR2 and/or FGFR3 gene alterations."

Oncology • FGFR2 • FGFR3

A Study to Evaluate KIN-3248 in Participants With Advanced Tumors Harboring FGFR2 and//or FGFR3 Gene Alterations (clinicaltrials.gov) - P1 | N=120 | Recruiting | Sponsor: Kinnate Biopharma | Not yet recruiting ➔ Recruiting

Enrollment open • Biliary Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor • Urothelial Cancer • FGFR2

First in human (FIH) Phase 1/1b study evaluating KIN-3248, a next-generation, irreversible pan-FGFR inhibitor (FGFRi), in patients (pts) with advanced cholangiocarcinoma (CCA) and other solid tumors harboring FGFR2 and/or FGFR3 gene alterations (CCF 2023) - No abstract available

Clinical • Metastases • P1 data • Biliary Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor • FGFR2 • FGFR3

Kinnate Biopharma Inc. Provides Full-Year 2022 Financial Results and Recent Corporate Updates (GlobeNewswire) - "...'2023 is shaping up to be a transformational year for Kinnate, one with several key clinical readouts anticipated, including the first monotherapy data disclosure on our lead product candidate, exarafenib, in an oral presentation at the upcoming AACR conference, initial data for the exarafenib plus binimetinib combination in the first half of 2023 and initial dose escalation data from our FGFR program, which is expected in the second half of this year'..."

P1 data • Oncology • Solid Tumor

First in human (FIH) phase 1/1b study evaluating KIN-3248, a next-generation, irreversible pan-FGFR inhibitor (FGFRi), in patients (pts) with advanced urothelial carcinoma (UC) and other solid tumors harboring FGFR2 and/or FGFR3 gene alterations. (ASCO-GU 2023) - P1 | "Reversible FGFRi are approved for the treatment of pts with locally advanced or metastatic urothelial carcinoma (UC) with susceptible FGFR2 or FGFR3 genetic alterations (erdafitinib) or metastatic CCA harboring FGFR2 gene fusions or rearrangements (pemigatinib and infigratinib). The study is actively enrolling patients in the US and globally. Clinical trial information: NCT05242822."

Clinical • Metastases • P1 data • Oncology • Solid Tumor • Urothelial Cancer • FGFR1 • FGFR2 • FGFR3

First in human (FIH) phase 1/1b study evaluating KIN-3248, a next-generation, irreversible pan-FGFR inhibitor (FGFRi), in patients (pts) with advanced cholangiocarcinoma (CCA) and other solid tumors harboring FGFR2 and/or FGFR3 gene alterations. (ASCO-GI 2023) - P1 | "Reversible FGFRi are approved for the treatment of pts with locally advanced or metastatic CCA harboring FGFR2 gene fusions or rearrangements (pemigatinib and infigratinib) or metastatic urothelial carcinoma (UC) with susceptible FGFR2 or FGFR3 genetic alterations (erdafitinib). The study is actively enrolling patients in the US and globally. Clinical trial information: NCT05242822."

Clinical • Metastases • P1 data • Biliary Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor • FGFR2 • FGFR3

Kinnate Biopharma Inc. Receives Fast Track Designation from the U.S. Food and Drug Administration for KIN-3248, an Investigational Pan-FGFR Inhibitor (GlobeNewswire) - "Kinnate Biopharma...announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation for Kinnate’s investigational pan-FGFR inhibitor, KIN-3248, for the treatment of patients with unresectable, locally advanced or metastatic cholangiocarcinoma (CCA) harboring fibroblast growth factor receptor 2 (FGFR2) gene fusions or other alterations, who have received at least one prior systemic therapy."

Fast track designation • Biliary Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Hematological Malignancies • Oncology • Solid Tumor • FGFR2

Kinnate Biopharma Inc. to Present Trials in Progress Poster for its Pan-FGFR Inhibitor, KIN-3248, at the 2023 ASCO Gastrointestinal Cancers Symposium and ASCO Genitourinary Cancers Symposium (GlobeNewswire) - "Kinnate Biopharma...announced the poster presentation of the design and rationale of a Phase 1 trial-in-progress (KN-4802, NCT05242822) evaluating the Company’s investigational pan-FGFR inhibitor, KIN-3248, at two upcoming American Society of Clinical Oncology (ASCO)-related conferences....This trial is currently enrolling across multiple sites in the U.S. and Taiwan, with initial dose escalation data anticipated in the second half of 2023."

Clinical protocol • P1 data • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

Developmental FGFR Inhibitors Are Active in FGFR+ Cholangiocarcinoma and Urothelial Carcinoma (OncLive) - "Borad: Alterations in the FGFR pathway are prevalent in many solid tumors and some hematological malignancies. Cancers where [FGFR2 fusions] are more prevalent include intrahepatic cholangiocarcinoma, where the prevalence is estimated to be in the 10% range. There are also FGFR2 mutations, which are found at a 3% to 4% prevalence mostly in intrahepatic cholangiocarcinoma, with a smaller prevalence in extrahepatic and hilar cholangiocarcinoma."

Interview

Ministry of Food and Drug Safety approves 4 clinical trials including treatment for chronic obstructive pulmonary disease [Google translation] (Health Korea News) - "USA Arcus Biosciences received approval for phase 1 clinical trial of 'AB521' capsule through IQVIA Korea, a clinical trial consignment agency. To study the safety, tolerability and pharmacokinetic profile of 'AB521' monotherapy in 11 Korean patients with clear cell renal cell carcinoma and other solid cancers....Novotech Asia Korea has been approved for a phase 1 study of 'KIN-3248 Tab', an anti-cancer drug targeting FGFR mutation. The safety, tolerability, pharmacokinetics, pharmacodynamics, and antitumor activity of 'KIN-3248' are investigated in six patients with advanced cancer with FGFR2 or FGFR3 gene mutations....Cliniface has been approved for phase 1b clinical trial of 'IDRX-42 Capsule', a treatment for gastrointestinal stromal tumors. The efficacy and safety of 'IDRX-42' will be explored in 15 domestic patients with metastatic or unresectable gastrointestinal stromal tumors."

New P1 trial • Trial status • Clear Cell Renal Cell Carcinoma • Gastrointestinal Cancer • Gastrointestinal Stromal Tumor • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma

Design and rationale of a first-in-human (FIH) phase 1/1b study evaluating KIN-3248, a next-generation, irreversible (irrev), pan-FGFR inhibitor (FGFRi), in adult patients with solid tumors harboring FGFR2 and/or FGFR3 gene alterations (NCT05242822). (ASCO 2022) - P1 | "There are currently 3 FDA-approved, reversible FGFRi for treatment of patients w/previously treated, locally advanced or metastatic (met) cholangiocarcinoma (CCA) harboring FGFR2 gene fusions/rearrangements (pemigatinib and infigratinib) or met urothelial carcinoma (UC) w/susceptible FGFR2 or FGFR3 genetic alterations (erdafitinib). Secondary objectives include pharmacokinetic and pharmacodynamic assessments including measures of FGFR pathway modulation. Enrollment is expected to commence in April 2022."

Clinical • P1 data • Biliary Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor • Urothelial Cancer • FGFR1 • FGFR2 • FGFR3

Kinnate Biopharma Inc. Announces Second Quarter 2022 Financial Results and Recent Corporate Updates (GlobeNewswire) - "Enrolling patients in the ongoing Phase 1 dose escalation portion of KN-8701 evaluating KIN-2787 at approximately 18 active trial sites, including in the U.S., Spain, France and Australia. Initial monotherapy data is expected in the fourth quarter of 2022, and data for the binimetinib combination in the first half of 2023....Enrolling patients in the Phase 1 dose escalation portion of KN-4802, with initial clinical data for KIN-3248 expected in the second half of 2023."

P1 data • Biliary Cancer • Cholangiocarcinoma • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

Kinnate Biopharma Inc. to Present Trial Design for its Pan-FGFR Inhibitor Product Candidate, KIN-3248, at ASCO 2022 (BioSpace) - "'A major limitation of approved and clinical-stage FGFR treatments is the emergence of secondary, on-target resistance mutations that reduce duration of response, highlighting the urgency to further research and develop more efficacious next-generation therapies for these patients,' said the trial's co-investigator and presenter Lipika Goyal, MD...'We are pleased to share additional details of this two-part Phase 1 trial-in-progress evaluating KIN-3248 at this year’s ASCO conference.'"

Media quote

Kinnate Biopharma Inc. to Present Trial Design for its Pan-FGFR Inhibitor Product Candidate, KIN-3248, at ASCO 2022 (GlobeNewswire) - "Kinnate Biopharma...announced the presentation of the design and rationale of a Phase 1 trial-in-progress (KIN-4802, NCT05242822) evaluating the Company’s pan-FGFR inhibitor product candidate, KIN-3248. The details will be presented during a poster session on June 6, 2022, at the Annual Meeting of the American Society of Clinical Oncology (ASCO)....The KN-4802 clinical trial (NCT05242822) is a multi-center, open-label, two-part study of approximately 120 patients to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary efficacy of KIN-3248 in adults with advanced tumors harboring FGFR2 and/or FGFR3 gene alterations....In addition, in an abstract published in the ASCO meeting proceedings, the Company also shared updates from its preclinical in vitro and in vivo preclinical studies evaluating KIN-2787 in combination with binimetinib."

Clinical protocol • Preclinical • Biliary Cancer • Biliary Tract Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

Kinnate Biopharma Inc. Reports First Quarter 2022 Financial Results and Provides Operational Updates (GlobeNewswire) - "Recent Business Highlights and Corporate Update: Abstract highlighting KIN-3248 was accepted for poster presentation during the ASCO 2022 Annual Meeting. The abstract is titled: Design and rationale of a first-in-human (FIH) phase 1/1b study evaluating KIN-3248, a next-generation, irreversible (irrev), pan-FGFR inhibitor (FGFRi), in adult patients with solid tumors harboring FGFR2 and/or FGFR3 gene alterations (NCT05242822)."

Clinical protocol • Biliary Tract Cancer • Cholangiocarcinoma • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer