AUR102 / Dr. Reddy’s, Exelixis - LARVOL DELTA

A Covalent CDK7 Inhibitor Overcomes Venetoclax Resistance and Induces Apoptosis via C-Myc/p53 Axis in Acute Myeloid Leukemia (SOHO 2024) - "Our study highlights that XL102 may be a promising therapeutic option in AML and can potentially overcome venetoclax resistance."

IO biomarker • Acute Myelogenous Leukemia • Leukemia • Lymphoma • Oncology • CDK1 • CDK2 • MCL1 • MYC

XL102-101: Study of XL102 as Single-Agent and Combination Therapy in Subjects With Solid Tumors (QUARTZ-101) (clinicaltrials.gov) - P1 | N=52 | Terminated | Sponsor: Exelixis | N=373 ➔ 52 | Trial completion date: Oct 2024 ➔ May 2024 | Active, not recruiting ➔ Terminated; Business reasons

Combination therapy • Enrollment change • Metastases • Trial completion date • Trial termination • Breast Cancer • Genito-urinary Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Metastatic Castration-Resistant Prostate Cancer • Oncology • Ovarian Cancer • Prostate Cancer • Solid Tumor • Triple Negative Breast Cancer • ER • HER-2 • PGR

XL102-101: Study of XL102 as Single-Agent and Combination Therapy in Subjects With Solid Tumors (QUARTZ-101) (clinicaltrials.gov) - P1 | N=373 | Active, not recruiting | Sponsor: Exelixis | Recruiting ➔ Active, not recruiting

Enrollment closed • Breast Cancer • Genito-urinary Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Metastatic Castration-Resistant Prostate Cancer • Oncology • Ovarian Cancer • Prostate Cancer • Solid Tumor • Triple Negative Breast Cancer • ER • HER-2 • PGR

Novel covalent CDK7 inhibitor potently induces apoptosis in acute myeloid leukemia and synergizes with Venetoclax. (PubMed, J Exp Clin Cancer Res) - P1 | "Taken together, XL102 with Venetoclax led to synergistic effects in overcoming resistance and provided a strong rationale for clinical evaluation of XL102 as a single agent and in combination with Venetoclax."

Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • Solid Tumor • BCL2 • CDK1 • MYC • PTPRC

A phase 1 study of the oral CDK7 inhibitor XL102 as a single agent and in combination therapy in patients With advanced solid tumors (QUARTZ-101): Initial results from the dose-escalation stage (SABCS 2022) - P1 | "Single-agent XL102 was well tolerated at the DLs tested. Updated data, as well as PK results, will be presented. Expansion cohorts in HR+BC, TNBC, EOC, and mCRPC will be initiated once a recommended dose for the expansion-cohort stage is determined."

Clinical • Combination therapy • P1 data • Breast Cancer • Genito-urinary Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Liposarcoma • Lung Cancer • Neuroendocrine Tumor • Oncology • Ovarian Cancer • Prostate Cancer • Sarcoma • Small Cell Lung Cancer • Solid Tumor • Triple Negative Breast Cancer • ER

Exelixis Announces Fourth Quarter and Full Year 2022 Financial Results and Provides Corporate Update (Businesswire) - "acceleration of the XB002 clinical program into full development by year-end; advancement of the XL102 QUARTZ-101 phase 1 study into the tumor-specific cohort-expansion stage and in planned combination cohorts; in collaboration with partner Cybrexa, progression of phase 1 clinical study for CBX-12, including dose-expansion cohorts; expected IND filing for ADU-1805 in the first quarter of 2023 by partner Sairopa; advancement of DCs XB010, XB014 and XB628 toward IND filings."

Clinical • Clinical protocol • IND • New P1 trial • Oncology • Solid Tumor

Exelixis Announces Preliminary Fourth Quarter and Full Year 2022 Financial Results, Provides 2023 Financial Guidance, and Outlines Key Priorities and Milestones for 2023 (Businesswire) - "In 2023, Exelixis intends to advance the first-in-human QUARTZ-101 phase 1 trial evaluating XL102, its potent, selective, irreversible and orally bioavailable small molecule CDK7 inhibitor into the cohort expansion and potential combination cohorts....Exelixis expects to evaluate the anti-tumor activity and efficacy of XL102 in additional patients in the single-agent dose-escalation cohorts, in the tumor-specific cohort-expansion stage and in planned combination cohorts....Exelixis expects its partner Cybrexa to continue to advance its phase 1 clinical study program for CBX-12 throughout 2023, including dose-expansion cohorts."

P1 data • Breast Cancer • Oncology • Ovarian Cancer • Solid Tumor

Exelixis Announces Initial Dose-Escalation Results from the First-in-Human Phase 1 Trial Evaluating XL102 in Patients with Advanced Solid Tumors at SABCS 2022 (Businesswire) - P1 | N=298 | QUARTZ-101 (NCT04726332) | Sponsor: Exelixis | "The data are being presented...at the 2022 San Antonio Breast Cancer Symposium (SABCS)....As of the September 7, 2022 data cutoff, 26 enrolled patients had been treated with single-agent oral XL102 at five dose levels: 20 mg once daily (n=3), 40 mg once daily (n=3), 80 mg once daily (n=7), 120 mg once daily (n=4) and 40 mg twice daily (n=9). The most common types of cancer for patients enrolled were hormone receptor-positive breast cancer (n=12), pancreatic cancer (n=3) and sarcoma (n=3)....As of data cutoff, no objective responses had been observed. Two patients with stable disease remain on study treatment as of the data cutoff: one with breast cancer and one with liposarcoma, with treatment durations of 46 and 45 weeks, respectively. One additional patient with breast cancer achieved durable stable disease as the best response and discontinued study treatment at 25 weeks."

P1 data • Breast Cancer • Gastrointestinal Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Pancreatic Cancer • Sarcoma • Solid Tumor

A phase 1 dose-escalation and expansion-cohort study of the oral CDK7 inhibitor XL102 as a single-agent and in combination therapy in patients (pts) with advanced solid tumors. (ASCO 2022) - P1 | "In the dose-escalation stage (modified interval 3+3 design), a maximum tolerated dose and/or recommended dose (MTD/RD) of XL102 will be established (primary endpoint) for use alone (solid tumors) and then for use in combination with standard dose fulvestrant (HR+BC) or abiraterone/prednisone (mCRPC); dose escalation will require ̃36 pts for the single-agent cohort and ̃15 pts for each combination cohort. The study began enrolling pts in February 2021 and is ongoing. Total enrollment is estimated to be up to 298 pts."

Clinical • Combination therapy • P1 data • Breast Cancer • Genito-urinary Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Ovarian Cancer • Prostate Cancer • Solid Tumor • Triple Negative Breast Cancer • CDK7

First in human phase 1 dose escalation and expansion study of the safety and pharmacokinetics of the oral CDK7 inhibitor XL102 as a single-agent and in combination therapy in patients with inoperable locally advanced or metastatic solid tumors, including breast cancer (SABCS 2021) - P1 | "In the dose-escalation stages (modified interval 3+3 design), a maximum tolerated (MTD) and/or recommended XL102 dose (RD) for use alone and in combination therapy with standard dose fulvestrant (HR+BC) or abiraterone/prednisone (mCRPC) will be established in independent strata. Accrual: The study began enrolling patients in February 2021 and is ongoing. Total enrollment estimated to be up to 298 subjects."

Clinical • Combination therapy • IO biomarker • P1 data • PK/PD data • Breast Cancer • Fallopian Tube Cancer • Genito-urinary Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Ovarian Cancer • Peritoneal Cancer • Prostate Cancer • Solid Tumor • Triple Negative Breast Cancer • CDK7

Exelixis Announces Second Quarter 2022 Financial Results and Provides Corporate Update (Businesswire) - "...'Moving into the second half of this year, we have much to look forward to, including the potential to further augment the CABOMETYX label through upcoming clinical data readouts expected from the CONTACT-01 and CONTACT-03 pivotal studies in non-small cell lung cancer and renal cell carcinoma, respectively, as well as anticipated clinical updates from our XL092, XB002 and XL102 pipeline programs'."

Clinical data • P3 data • Genito-urinary Cancer • Kidney Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Thoracic Cancer • Urothelial Cancer

Exelixis Announces Preliminary Fourth Quarter and Full Year 2021 Financial Results, Provides 2022 Financial Guidance, and Outlines Key Priorities and Milestones for 2022 (Businesswire) - "Anticipated Pipeline Milestones: (i) Expansion of the XL102 clinical program:...Exelixis expects to provide clinical updates and present initial data from the ongoing phase 1 study of XL102 in 2022; (ii) Initiation of phase 1 trial for XL114: Exelixis expects to initiate dosing in the phase 1 trial of XL114 in patients with non-Hodgkin’s lymphoma during the first half of 2022."

P1 data • Trial status • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor

"Recall $EXEL in the CDK7i with XL102 (from Aurigene) too fwiw https://t.co/ivcXlv6VKr" (@BiotechElmo)

Study of XL102 as Single-Agent and Combination Therapy in Subjects With Solid Tumors (clinicaltrials.gov) - P1; N=298; Recruiting; Sponsor: Exelixis

Clinical • Combination therapy • New P1 trial • Breast Cancer • Genito-urinary Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Ovarian Cancer • Prostate Cancer • Solid Tumor • Triple Negative Breast Cancer • ER • HER-2 • PGR

Exelixis Announces Fourth Quarter and Full Year 2020 Financial Results and Provides Corporate Update (Businesswire) - "...'In parallel, we’re focused on the rapid development of XL092, with plans to advance this next-generation oral tyrosine kinase inhibitor into pivotal trials this year. We also continue to make significant progress on our early-stage pipeline, having recently begun phase 1 development of XL102, our small molecule CDK7 inhibitor, and plan to file an Investigational New Drug application for XB002, our first antibody-drug conjugate, once the drug product release assays are finalized'."

IND • Pipeline update • Oncology

Exelixis Announces Initiation of Phase 1 Trial Evaluating XL102 as a Single Agent and in Combination with Other Anti-Cancer Agents in Patients with Advanced or Metastatic Solid Tumors (Businesswire) - "Exelixis, Inc....announced initiation of the first-in-human phase 1 trial evaluating the safety, tolerability, pharmacokinetics and preliminary anti-tumor activity of XL102 alone or in combination with other anti-cancer agents in patients with inoperable locally advanced or metastatic solid tumors....The XL102-101 trial is a phase 1, open-label dose-escalation and cohort-expansion study evaluating the safety, tolerability, pharmacokinetics, anti-tumor activity and effect on biomarkers of XL102 administered orally alone and in multiple combination regimens in up to 298 patients with advanced solid tumors."

Trial status • Oncology • Solid Tumor

Exelixis Announces Preliminary Fourth Quarter and Full Year 2020 Financial Results, Provides 2021 Financial Guidance, and Outlines Key Priorities and Anticipated Milestones For 2021 (Businesswire) - "Exelixis is currently enrolling patients into the dose escalation cohorts of the phase 1b clinical trial of XL092 in combination with atezolizumab, and expects to initiate enrollment in the clear cell and non-clear cell RCC...As data from these cohorts mature and are supportive, XL092 could enter pivotal trials over the course of 2021...expects to initiate a phase 1 trial of XL102 (formerly known as AUR102), alone or in combination therapy for the treatment of inoperable, locally advanced or metastatic solid tumors."

Enrollment status • New P1 trial • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Exelixis In-Licenses Aurigene’s Novel CDK7 Inhibitor and Files Investigational New Drug Application for Phase 1 Clinical Trial in Advanced Solid Tumors (Businesswire) - “Exelixis, Inc…and Aurigene today announced that Exelixis has exercised its exclusive option for Aurigene’s novel CDK7 inhibitor under the companies’ July 2019 agreement. Exelixis has now assumed responsibility for the future clinical development, commercialization, and global manufacturing of the compound now known as XL102 (formerly AUR102). Exelixis also announced that it has submitted an Investigational New Drug Application (IND) to the U.S. Food and Drug Administration (FDA) to evaluate XL102 alone or in combination therapy for the treatment of inoperable locally advanced or metastatic solid tumors…In addition, Exelixis and Aurigene initiated three Aurigene-led drug discovery programs on mutually agreed upon targets, in exchange for additional upfront option payments of $2.5 million per program.”

IND • Licensing / partnership • Oncology • Solid Tumor

Exelixis Announces Third Quarter 2020 Financial Results and Provides Corporate Update (Exelixis Press Release) - "The...EXAMINER Phase 4 trial was designed to enroll up to 250 patients, and top-line results from the trial are anticipated later this year...Based on current event rates, Exelixis anticipates announcing top-line results...[from] the COSMIC-312 Phase 3 Pivotal Trial in Previously Untreated Hepatocellular Carcinoma...in the first half of 2021...AUR102 could be the subject of an IND later this year."

IND • P3 data: top line • P4 data • Hepatocellular Cancer • Oncology • Thyroid Gland Carcinoma

[VIRTUAL] Potent anti-tumor activity of AUR102, a selective covalent inhibitor of CDK7 (AACR-NCI-EORTC 2020) - "In vitro combination studies showed synergy with fulvestrant in a ER+ breast cancer cell line (MCF-7), with docetaxel in a prostate cancer cell line (DU-145), and venetoclax in a mantle cell lymphoma cell line (Z-138). AUR102 exhibits potent anti-tumor activity in in vitro and in vivo models. Findings presented here support further evaluation of AUR102 in the clinic for the treatment of cancer both as a single agent and in combination with approved anticancer agents."

Breast Cancer • Diffuse Large B Cell Lymphoma • Genito-urinary Cancer • Hematological Malignancies • Hormone Receptor Breast Cancer • Leukemia • Lymphoma • Mantle Cell Lymphoma • Oncology • Prostate Cancer • Solid Tumor • Triple Negative Breast Cancer

[VIRTUAL] Potent anti-tumor activity of AUR102, a selective covalent inhibitor of CDK7 (AACR-NCI-EORTC 2020) - "In vitro combination studies showed synergy with fulvestrant in a ER+ breast cancer cell line (MCF-7), with docetaxel in a prostate cancer cell line (DU-145), and venetoclax in a mantle cell lymphoma cell line (Z-138). AUR102 exhibits potent anti-tumor activity in in vitro and in vivo models. Findings presented here support further evaluation of AUR102 in the clinic for the treatment of cancer both as a single agent and in combination with approved anticancer agents."

Breast Cancer • Diffuse Large B Cell Lymphoma • Genito-urinary Cancer • Hematological Malignancies • Hormone Receptor Breast Cancer • Leukemia • Lymphoma • Mantle Cell Lymphoma • Oncology • Prostate Cancer • Solid Tumor • Triple Negative Breast Cancer

Exelixis and Aurigene Announce That Promising Preclinical Data to Be Presented at the ENA Symposium Support the Clinical Development of a Novel CDK7 Inhibitor (Businesswire) - "Exelixis...today disclosed new preclinical data showing that AUR102 has potent anti-tumor activity in a large panel of cancer cell lines. AUR102 is a potent, selective, and orally bioavailable covalent inhibitor of cyclin-dependent kinase 7 (CDK7), which is an important regulator of the cellular transcriptional and cell cycle machinery. Exelixis has an exclusive option for AUR102 under its July 2019 exclusive collaboration, option and license agreement with Aurigene. The new data will be presented in a poster (Abstract 170) at the 32nd EORTC-NCI-AACR (ENA) Symposium, which is being held virtually on October 24-25, 2020."

Preclinical • Oncology • Solid Tumor