Jounce Therapeutics Advances in INNATE Study of JTX-8064 (LILRB2 / ILT4 Inhibitor) Monotherapy and Pimivalimab (PD-1 Inhibitor) Combination Therapy in Patients with Advanced Solid Tumors | Antibody
Jounce Therapeutics Advances in INNATE Study of JTX-8064 (LILRB2 / ILT4 Inhibitor) Monotherapy and Pimivalimab (PD-1 Inhibitor) Combination Therapy in Patients with Advanced Solid Tumors
Posted on Saturday 09 October 2021 11:19
– Recruitment initiated in the extension cohorts of specific tumor monotherapy and pimivalimab combination –
– Enrollment in monotherapy and in combination with the increase in the dose of pimivalimab completed –
CAMBRIDGE, MA, USA I October 07, 2021 I Jounce Therapeutics, Inc. (NASDAQ: JNCE), a clinical-stage company focused on the discovery and development of novel cancer immunotherapies and predictive biomarkers, today announced the launch of patient recruitment into the INNATE expansion cohorts tumor specific for both JTX-8064 monotherapies. and the combination therapy of JTX-8064 with its internal PD-1 inhibitor, pimivalimab. JTX-8064, the first tumor-associated macrophage candidate developed from Jounce’s translational scientific platform, is a humanized IgG4 monoclonal antibody designed to specifically bind to the Leukocyte Immunoglobulin Like Receptor B2 (LILRB2 / ILT4) macrophage receptor. By inhibiting the binding of LILRB2 with its ligands, JTX-8064 reprograms immunosuppressive macrophages to an immunoactive state in preclinical studies, potentially improving T cell response and anti-tumor immunity.
“We are very pleased to announce that we have started assaying patients in the tumor-specific JTX-8064 monotherapy and pimivalimab combination extension cohorts of our INNATE study,” said Beth Trehu, MD, medical director of Jounce Therapeutics. “We have made tremendous progress in INNATE, having advanced the study from the onset of dose escalation in monotherapy to the initiation of tumor-specific combination extension cohorts, proof of concept , in just nine months. These advancements have been driven by the continued dedication of our employees, the enthusiasm of the researchers and, based on science, our belief that the mechanism of action of JTX-8064 has the potential to address the major emerging unmet need. in immuno-oncology, overcoming resistance to PD- (L) 1 inhibitors. We look forward to sharing updates on our continued execution of the INNATE study. “
The proof of concept (POC) expansion cohorts in INNATE will target three different segments of the OI patient populations; first, patients whose tumors have progressed on or after a previous inhibitor of PD-1 or PD-L1 (PD- (L) 1i) and whose tumors have shown primary or acquired resistance; second, IO-naive patients with tumors for which no PD- (L) 1i treatment is approved; and third, IO naive patients with tumors that have PD- (L) 1i approval. The POC extension cohorts in INNATE follow a two-step Simon design with the potential to enroll up to 29 patients per combined cohort and 47 patients in the monotherapy cohort if pre-specified criteria are met. If the POC is established after evaluating 29 or 47 patients, respectively, Jounce intends to quickly move JTX-8064 into registration trials on a cohort-by-cohort basis. INNATE will also assess potential pharmacodynamic and predictive biomarkers to guide future development, in line with Jounce’s philosophy of developing the right immunotherapies for the right patients.
The INNATE trial (NCT04669899) is divided into 4 parts:
- Part 1: Dose escalation in JTX-8064 monotherapy in solid tumors (completed July 2021)
- Part 2: JTX-8064 + pimivalimab dose escalation in solid tumors (recruitment completed)
- Part 3: JTX-8064 Monotherapy Expansion Cohort in 2sd– to 4e-line PD- (L) 1i naive, platinum resistant ovarian cancer (initiated in August 2021)
- Part 4: JTX-8064 + pimivalimab in indication-specific extension cohorts (initiated October 2021)
- Combination expansion cohorts include:
- 2sd– to 3rd-line non-small cell lung cancer that has progressed during or after PD- (L) 1i
- 2sd-line + clear cell renal carcinoma that has progressed during or after PD- (L) 1i
- 2sd– to 4e-line of triple negative breast cancer that has progressed during or after PD- (L) 1i
- 2sd– to 3rd-line cutaneous squamous cell carcinoma that has progressed on or after PD- (L) 1i
- 1st-line PD- (L) 1i naive, squamous cell carcinoma of the head and neck PD-L1 +
- 2sd– to 4e-line PD- (L) 1i naive, platinum resistant, ovarian cancer
- 2sd– to 4e-line PD- (L) 1i naive, undifferentiated pleomorphic sarcoma and liposarcoma
- Combination expansion cohorts include:
JTX-8064 is a humanized IgG4 monoclonal antibody designed to bind specifically to the leukocyte-like Immunoglobulin receptor B2 (LILRB2 / ILT4) and block interactions with its ligands. JTX-8064 is the first tumor-associated macrophage candidate developed from Jounce’s translational scientific platform. Preclinical data presented at the 2020 Annual Meeting of the Society for Immunotherapy of Cancer and the 2019 and 2021 Annual Meetings of the American Association for Cancer Research support the development of JTX-8064 as a novel immunotherapy to reprogram immunosuppressive macrophages and strengthen anti-tumor immunity. Phase 1 clinical trial named INNATE (NCT04669899) of JTX-8064 as monotherapy and in combination with Jounce’s internal anti-PD-1 inhibitor, pimivalimab (formerly JTX-4014) is currently recruiting patients with advanced solid tumors in expanding tumor-specific cohorts.
Pimivalimab (formerly JTX-4014) is a well-characterized fully human IgG4 monoclonal antibody designed to block binding to PD-L1 and PD-L2. Pimivalimab demonstrated a sustained overall response rate of 17% in a phase 1 trial involving 18 heavily pretreated PD- (L) 1 inhibitor naive patients, which excluded all tumor types for which inhibitors of PD- (L) 1 have been approved. In this Phase 1 trial, pimivalimab was shown to have an acceptable safety profile. Pimivalimab is currently being evaluated in the Phase 1 INNATE trial (NCT04669899) in combination with JTX-8064, an LILRB2 (ILT4) inhibitor. Pimivalimab is also being evaluated in the SELECT Phase 2 clinical trial (NCT04549025) in combination with vopratelimab, a clinical stage monoclonal antibody that binds and activates ICOS, the inducible T cell co-stimulator, a protein present on the surface of certain T cells frequently found in many solid tumors.
About Jounce Therapeutics:
Jounce Therapeutics, Inc. is a clinical-stage immunotherapy company dedicated to transforming cancer treatment by developing therapies that enable the immune system to attack tumors and deliver lasting benefits to patients through a focused approach. on biomarkers. Jounce currently has several development programs underway while simultaneously advancing additional early stage assets of its robust discovery engine based on its translational science platform. Jounce’s priority program, JTX-8064, is an LILRB2 (ILT4) receptor antagonist that has been shown to reprogram tumor-associated immunosuppressive macrophages into an anti-tumor state in preclinical studies. Jounce’s most advanced product candidate, vopratelimab, is a monoclonal antibody that binds and activates ICOS, and is currently under investigation in the phase 2 SELECT trial. Pimivalimab is a PD-1 inhibitor intended for use in combination in the INNATE and SELECT assays and with Jounce’s larger pipeline. Additionally, Jounce has granted exclusive worldwide rights to GS-1811 (formerly JTX-1811), a monoclonal antibody targeting CCR8 and designed to selectively deplete regulatory T cells in the tumor microenvironment, to Gilead Sciences, Inc. more information, please visit www. jouncetx.com.
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