1stOncology™: Cancer Intelligence Service – Page 10812 – 1stOncology is recognized as a Top 10 Global Pharma Analytic Provider

Intensity Therapeutics Doses First Patient with Combination of INT230-6 and Bristol Myers Squibb’s Yervoy® in a Phase 2 Study

On September 17, 2020 Intensity Therapeutics, Inc., a clinical-stage biotechnology company developing proprietary technology and products to kill tumors and increase immune system recognition of the cancer, reported that the first patient has been dosed with a combination of INT230-6, the Company’s lead investigational product, and Yervoy (ipilimumab), Bristol Myers Squibb’s (BMS) Cytotoxic T Lymphocyte-Associated Antigen 4 (CTLA-4) immune checkpoint inhibitor therapy in Phase 2 (Press release, Intensity Therapeutics, SEP 17, 2020, View Source [SID1234565284]). The combination is being studied in a series of phase 2 expansion cohorts within IT-01, Intensity’s ongoing international clinical study (NCT03058289), which evaluates the safety and efficacy of the combination in patients with three different types of cancer (breast cancer, liver cancer, and sarcoma).
"Bringing INT230-6 into phase 2 human testing in combination with Yervoy is an important achievement for Intensity Therapeutics," commented Lewis H. Bender, President and Chief Executive Officer of Intensity Therapeutics. "Our preclinical and clinical data have resulted in favorable safety for INT230-6 as a single agent or in combination with immunotherapies. The phase 1 escalation portion of our INT230-6 development program is complete. We are excited about starting the phase 2 portion of our trial using INT230-6 at proper doses early in the treatment process especially in combination with Yervoy."

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

Schedule Your 30 min Free Demo!

"The phase 2 Yervoy combination studies accrue patients with breast cancer, liver cancer, and sarcoma that are refractory to standard of care and have high unmet medical need" said Ian B. Walters, MD, Chief Medical Officer of Intensity Therapeutics. "We are optimistic that our trial design enables us to quickly evaluate safety and efficacy in patients having cancers that are difficult to treat. Physicians desperately need better therapies for their patients. Our approach to safely debulk tumors and recruit an immune response by releasing tumor antigens derived from the patient’s own tumors may be amplified by blocking a checkpoint signal using Yervoy."

About INT230-6

INT230-6, Intensity’s lead proprietary product candidate, is designed for direct intratumoral injection. INT230-6 was discovered using Intensity’s proprietary DfuseRxSM technology platform. The drug is comprised of two proven, potent anti-cancer agents, cisplatin and vinblastine, and a penetration enhancer molecule that helps disperse the drugs throughout tumors for diffusion into cancer cells. In preclinical studies, INT230-6 eradicated tumors by a combination of direct tumor killing, release of tumor antigens and recruitment of immune cells to the tumor. Results generated by both the Company and the National Cancer Institute (NCI) showed treatment with INT230-6 in in vivo models of severe cancer resulted in substantial improvement in overall survival compared to standard therapies. Further, INT230-6 provided complete responses in animals with long-term protection from multiple re-challenges of the initial cancer and resistance to other cancers. The Company’s research published in the International Journal of Molecular Sciences earlier this year and published jointly with the NCI as part of Intensity’s collaborative research, published in July 2019 in the Journal OncoImmunology, also showed strong synergy when INT230-6 was combined with anti-PD-1 and anti-CTLA-4 antibodies. INT230-6 is being evaluated in a Phase 1/2 clinical study (NCT03058289) in patients with various advanced solid tumors. There have been no dose limiting adverse events observed in patients to date, even when dosing into deep tumors in the lung and liver. Several patients demonstrated tumor shrinkage, symptomatic improvement, and evidence of cancer cell death and immune cell activation on tumor biopsy. In the combination cohort with pembrolizumab the Company reported the safety of the combination was comparable to INT230-6 monotherapy.

Halozyme Announces Poster Presentation Of Data From Roche’s Phase 1b Study Evaluating Atezolizumab For Subcutaneous Administration Utilizing Enhanze® In Non-Small Cell Lung Cancer

On September 17, 2020 Halozyme Therapeutics, Inc. (NASDAQ: HALO) reported that its collaborator, Roche, presented a poster with data from Part 1 of its Phase 1b study (IMscin001) evaluating atezolizumab (Tecentriq) for subcutaneous administration utilizing Halozyme’s ENHANZE technology in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) at the ESMO (Free ESMO Whitepaper) Virtual Congress 2020 (Press release, Halozyme, SEP 17, 2020, View Source [SID1234565283]).

The Phase 1b dose-finding study enrolled 67 patients with advanced/metastatic NSCLC previously treated with chemotherapy (no prior cancer immunotherapy) in 3 cohorts. The poster concluded that atezolizumab utilizing ENHANZE was well tolerated, provided similar exposure as atezolizumab IV and that results support further development of subcutaneous atezolizumab in IMscin001 Part 2, a confirmatory phase III study.

"We are pleased that the results from Roche’s Phase 1b evaluating atezolizumab with ENHANZE support continued development in a Phase 3 study," said Dr. Helen Torley, president and chief executive officer.

The subcutaneous formulation of atezolizumab is being developed to potentially allow faster administration via subcutaneous injection under the skin, compared to the original intravenous (IV) formulation, thereby significantly reducing a patient’s time spent receiving treatment.

BOEHRINGER INGELHEIM AND MIRATI THERAPEUTICS ANNOUNCE CLINICAL COLLABORATION TO STUDY BI 1701963, A SOS1::PAN-KRAS INHIBITOR IN COMBINATION WITH MRTX849, A KRAS G12C SELECTIVE INHIBITOR

On September 17, 2020 Boehringer Ingelheim and Mirati Therapeutics, Inc. (NASDAQ: MRTX) reported a clinical collaboration to evaluate the combination of BI 1701963, a SOS1::pan-KRAS inhibitor blocking KRAS independent of mutation type, and MRTX849, a KRAS G12C selective inhibitor in patients with solid tumors that harbor the KRAS G12C mutation (Press release, Boehringer Ingelheim, SEP 17, 2020, View Source [SID1234565282]). The collaboration will investigate the potential of this combination to provide more effective and durable responses for patients with lung and colorectal cancers who currently have limited treatment options.

Preclinical data suggest that the combination of a KRAS G12C inhibitor with a SOS1::pan-KRAS inhibitor results in increased anti-tumor activity based on the complementary mechanisms of these targeted oncology agents. By shifting the equilibrium from active KRAS(ON) towards the inactive KRAS(OFF) form, SOS1::pan-KRAS inhibitors have the potential to sensitize KRAS G12C mutant tumors to covalent KRAS G12C inhibitors that bind to KRAS(OFF).

"We look forward to collaborating with Boehringer Ingelheim to test this combination in clinical trials," said Joseph Leveque, M.D., Executive Vice President and Chief Medical Officer of Mirati Therapeutics, Inc. "This collaboration is aligned with the broad and aggressive development strategy we have for MRTX849 and brings the potential for another therapeutic option to patients with KRAS G12C mutations."

"We are excited to partner with Mirati in our ambition to make a difference for people living with KRAS-driven cancers. Combining our SOS1::pan-KRAS inhibitor with the mutation specific G12C inhibitor could be a win-win approach enhancing the response to therapy," said Victoria Zazulina, M.D., Global Medical Head for Oncology at Boehringer Ingelheim. "We have a comprehensive KRAS program including the first SOS1::pan-KRAS inhibitor in the clinic, BI 1701963, for which we are exploring several combinations to optimize its therapeutic benefit in broad patient populations."

Under the terms of the non-exclusive collaboration, Mirati will be the sponsor of the trial and Boehringer Ingelheim and Mirati will jointly share the costs of and oversee clinical development for the combined therapy.

About MRTX849
MRTX849 is an investigational, orally available small molecule that is designed to potently and selectively inhibit a form of KRAS, which harbors a substitution mutation (G12C). KRAS G12C mutations are present in approximately 14% of non-small cell lung cancer (NSCLC) adenocarcinoma patients, in 3-4% of colorectal cancer patients, and in subsets of other types of cancer. Tumors characterized by KRAS G12C mutations are commonly associated with poor prognosis and resistance to therapy, and patients with these mutations have few treatment options. MRTX849 is being evaluated in a Phase 1/2 trial treating patients with molecularly identified, KRAS G12C-positive advanced solid tumors and in the first quarter of 2020, enrollment began in the registration enabling cohort in monotherapy NSCLC, colorectal cancer and pancreatic cancer.

About BI 1701963
BI 1701963 is an investigational, orally available small molecule, that is designed to bind to the catalytic domain of SOS1 preventing the interaction with KRAS(OFF) and simultaneously blocking SOS1 driven feedback. This reduces the formation of KRAS(ON) and in consequence inhibits MAPK pathway signaling in KRAS-dependent cancers. The selective inhibition of SOS1 is a therapeutic concept that could allow KRAS blockade irrespective of KRAS mutation type (pan-KRAS approach). SOS1::KRAS inhibitors exhibit activity on a broad spectrum of KRAS alleles, including all major G12D/V/C and G13D oncoproteins, as recently published by Hofmann MH, et al. in Cancer Discovery, a journal of the American Association of Cancer Research (AACR) (Free AACR Whitepaper). BI 1701963 is currently being evaluated in a Phase I clinical trial in patients with advanced KRAS-mutated cancers to evaluate safety, tolerability, pharmacokinetic and pharmacodynamic properties, and preliminary efficacy of BI 1701963 alone and in combination with MEK inhibitors.

Lineage Cell Therapeutics to Present at FORCE Wealth Virtual Fireside Chat on September 23, 2020

On September 17, 2020 Lineage Cell Therapeutics, Inc. (NYSE American and TASE: LCTX), a clinical-stage biotechnology company developing novel cell therapies for unmet medical needs, reported that Brian M. Culley, Chief Executive Officer, and Brandi L. Roberts, Chief Financial Officer, will be participating in a FORCE Wealth Virtual Fireside Chat on September 23, 2020 at 12:00 pm Eastern Time / 9:00 am Pacific Time (Press release, Lineage Cell Therapeutics, SEP 17, 2020, View Source [SID1234565281]). Jason McCarthy, Ph.D., Senior Managing Director, Biotechnology, Maxim Group, LLC will host the fireside chat with Lineage management.

Interested investors can access the live presentation on the Events and Presentations section of Lineage’s website and archived presentations will be available for 30 days. Additional videos are available on the Media page of the Lineage website, located at www.lineagecell.com/media/.

ADC Therapeutics Announces Presentation of Preliminary Findings from Phase 1b Clinical Trial of Camidanlumab Tesirine (Cami) in Advanced Solid Tumors at ESMO Virtual Congress 2020

On September 17, 2020 ADC Therapeutics SA (NYSE: ADCT), a late clinical-stage oncology-focused biotechnology company pioneering the development and commercialization of highly potent and targeted antibody drug conjugates (ADCs) for patients with hematological malignancies and solid tumors, reported the presentation of an on-demand e-poster titled "First-in-Human Study of Camidanlumab Tesirine (ADCT-301, Cami), an anti-CD25 Targeted Therapy in Patients with Advanced Solid Tumors: Pharmacokinetics (PK) and Biomarker Evaluation" (abstract #1030P) at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Virtual Congress 2020 (Press release, ADC Therapeutics, SEP 17, 2020, View Source [SID1234565280]).

The ongoing, multicenter, open-label Phase 1b clinical trial of camidanlumab tesirine (Cami, formerly ADCT-301) is enrolling patients with selected locally advanced or metastatic solid tumors. The primary objective of the trial is to characterize the safety and tolerability of Cami and identify recommended dose(s) and schedule(s) for future studies.

"The early PK and biomarker data from our ongoing first-in-human trial of Cami as a single agent in solid tumors support the continued evaluation of its immune-mediated anti-tumor activity through the depletion of CD25-positive regulatory T cells in the tumor microenvironment," said Jay Feingold, MD, PhD, Senior Vice President and Chief Medical Officer of ADC Therapeutics. "What we have observed thus far in the Phase 1b trial, as well as in a preclinical study that was recently published in the Journal for ImmunoTherapy of Cancer, also indicates that the exploration of Cami in combination with other immuno-modulating therapies is warranted. We look forward to advancing Cami as a novel immuno-oncology approach for the treatment of solid tumors while we also continue to evaluate Cami in our pivotal Phase 2 trial in patients with relapsed or refractory Hodgkin lymphoma."

Preliminary Data from Phase 1b Trial of Cami in Advanced Solid Tumors at ESMO (Free ESMO Whitepaper)

As of July 31, 2020, 41 patients were enrolled and treated every three weeks at doses of: 20 (n=3), 30 (n=5), 45 (n=5), 60 (n=5), 80 (n=8), 100 (n=7), 125 (n=6), and 150 µg/kg (n=2). The two most common tumor types were colorectal and pancreatic (both n=14).

Preliminary findings indicate that treatment with Cami is associated with clinically relevant modulation of immune cells, both in the circulation and in tumor tissue, with mild to moderate inter-patient variability in tumor tissue. Increases in soluble CD25 and cytokines in serum post-dosing followed a similar pattern to increases in CD4-positive and CD8-positive T cells, suggesting an increase in activated lymphocytes. Changes in lymphocyte subpopulations in the blood resulted in a dose-related increase in the effector T cell (Teff) to regulatory T cell (Treg) ratio.

The e-poster became available on the ESMO (Free ESMO Whitepaper) Congress platform today and will be available until 20:00 CEST / 2 p.m. EDT on Monday, September 21, 2020. Thereafter, the e-poster will be available on ADC Therapeutics’ website, www.adctherapeutics.com.

For more information about the company’s Phase 1b clinical trial of Cami in solid tumors, visit www.clinicaltrials.gov (identifier NCT03621982).

About Camidanlumab Tesirine (Cami)

Camidanlumab tesirine (Cami, formerly ADCT-301) is an antibody drug conjugate (ADC) comprised of a monoclonal antibody that binds to CD25 (HuMax-TAC, licensed from Genmab A/S), conjugated to the pyrrolobenzodiazepine (PBD) dimer payload, tesirine. Once bound to a CD25-expressing cell, ADCT-301 is internalized into the cell where enzymes release the PBD-based warhead killing the cell. This applies to CD25-expressing tumor cells, and also to CD25-expressing Tregs. The intra-tumoral release of its PBD warhead may also cause bystander killing of neighboring tumor cells and PBDs have also been shown to induce immunogenic cell death. All of these properties of Cami may enhance immune-mediated anti-tumor activity. Cami is being evaluated in a pivotal Phase 2 clinical trial in patients with relapsed or refractory Hodgkin lymphoma (HL), as well as in a Phase 1a/1b clinical trial in patients with relapsed or refractory HL and non-Hodgkin lymphoma and a Phase 1b clinical trial in solid tumors.