On April 9, 2021 Iovance Biotherapeutics, Inc. (NASDAQ: IOVA), a late-stage biotechnology company developing novel T cell-based cancer immunotherapies, reported data from Cohort 2 in the C-144-01 study of lifileucel in advanced melanoma (Press release, Iovance Biotherapeutics, APR 9, 2021, View Source [SID1234577772]). These data will be part of an oral presentation in a Clinical Trials Plenary Session at the upcoming American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2021 Annual Meeting.

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"We are very excited to report our latest Cohort 2 melanoma data in an oral presentation at AACR (Free AACR Whitepaper)," said Maria Fardis, Ph.D., President and Chief Executive Officer of Iovance Biotherapeutics. "The long term follow up data show that median duration of response was not reached at 28.1 months of median study follow up. Furthermore, overall response rate remained at 36.4 percent and we saw a continued deepening of response in 17 percent of the patients. The data continue to demonstrate durability and depth of our lifileucel TIL therapy response after a one-time treatment, in a difficult to treat patient population with advanced melanoma. We are honored that AACR (Free AACR Whitepaper) has chosen our melanoma Cohort 2 data to be featured in a clinical trials plenary session."

Jason Chesney, M.D., Ph.D., Director, James Graham Brown Cancer Center, University of Louisville and C-144-01 study investigator stated, "Melanoma patients who have progressed on immune checkpoint and BRAF/MEK inhibitors are among the most challenging patients for oncologists to treat. The updated results of the C-144-01 study continue to demonstrate that autologous tumor infiltrating lymphocytes (TILs; lifileucel) induce durable clinical responses in 36 percent of patients in the study. This study also creates opportunities for additional trials of TILs in many other cancer types and in combination with immunomodulatory agents."

The Cohort 2 data are available in the abstract titled, "Lifileucel (LN-144), a cryopreserved autologous tumor infiltrating lymphocyte (TIL) therapy in patients with advanced (unresectable or metastatic) melanoma: durable duration of response at 28-month follow up." Data highlights as of the December 14, 2020 data cut extract used for the abstract submitted to AACR (Free AACR Whitepaper) were as follows:

Lifileucel showed a 36.4% overall response rate (4.5% complete responses and 31.8% partial responses) and median duration of response (DOR) was not reached at 28.1 months of median study follow up as assessed by investigators (n=66).
The Cohort 2 patients had heavily pretreated metastatic melanoma with high baseline disease burden. They have progressed on multiple prior therapies (3.3 mean prior therapies), including anti-PD1 and BRAF/MEK inhibitors if BRAFV600 mutation positive.
The adverse event profile was consistent with the underlying advanced disease, lymphodepletion and IL-2 regimens, with no additional adverse events emerging over time.
The abstract is available in the AACR (Free AACR Whitepaper) Online Meeting Planner at www.aacr.org and on the Iovance website at www.iovance.com/our-science/publications. The data from the abstract will be highlighted in additional detail at the AACR (Free AACR Whitepaper) 2021 Annual Meeting. Details of the oral presentation are as follows:

Abstract Title: Lifileucel (LN-144), a cryopreserved autologous tumor infiltrating lymphocyte (TIL) therapy in patients with advanced (unresectable or metastatic) melanoma: durable duration of response at 28-month follow up
Authors: Jason Alan Chesney, MD, PhD, et al.
Abstract Number: 5329
Presentation Number: CT008
Session Title: Immunooncology and Cell Therapy Trials
Session Date and Time: Saturday, April 10, 2021, 4:45 PM – 5:00 PM ET
Location: AACR (Free AACR Whitepaper) Virtual Annual Meeting 2021 at www.aacr.org
In addition to the oral presentation, three Iovance poster presentations at AACR (Free AACR Whitepaper) will highlight the design of clinical trials in progress in solid tumors and chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL). These posters are intended to educate physicians about study design and will not include clinical data. Posters will be available from 8:30 a.m. ET on Saturday, April 10 through Monday, June 21, 2021 in the Virtual ePoster Hall at www.aacr.org and on the Iovance website at www.iovance.com/our-science/publications.

Abstract Title: A Phase 2, multicenter study of autologous tumor infiltrating lymphocytes (TIL) (LN-144/LN-145/LN-145-S1) in patients with solid tumors (IOV-COM-202)
Authors: Scott Gettinger, MD, et al.
Abstract Number: CT235
Abstract Title: A Phase 1/2 study evaluating the safety and efficacy of IOV-2001 in patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) (IOV-CLL-01)
Authors: Meixiao Long, MD, PhD, et al.
Abstract Number: CT244
Abstract Title: A phase 2 multicenter study of autologous tumor infiltrating lymphocytes (TIL; LN-145) cell therapy in patients with metastatic non-small cell lung cancer (IOV-LUN-202)
Authors: Erminia Massarelli, MD, PhD, et al.
Abstract Number: CT246

On April 9, 2021 Mersana Therapeutics, Inc. (NASDAQ:MRSN), a clinical-stage biopharmaceutical company focused on discovering and developing a pipeline of antibody-drug conjugates (ADCs) targeting cancers in areas of high unmet medical need, reported the initiation of patient dosing in UPLIFT, a single-arm registration strategy to evaluate the safety and efficacy of upifitamab rilsodotin (UpRi, XMT-1536) in patients with platinum-resistant ovarian cancer who have received up to four lines of therapy (Press release, Mersana Therapeutics, APR 9, 2021, View Source [SID1234577790]).

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"UpRi has demonstrated clinically meaningful activity, a biomarker-response relationship and a differentiated tolerability profile without severe neutropenia, peripheral neuropathy or ocular toxicity in heavily pretreated ovarian cancer patients who have limited options and poor prognosis. The UPLIFT strategy is critical to bringing this promising agent to patients waiting for new therapies," said Anna Protopapas, President and Chief Executive Officer of Mersana Therapeutics.

UPLIFT will evaluate the safety and efficacy of UpRi in patients with platinum-resistant ovarian cancer who have received up to four lines of therapy. Consistent with the bevacizumab label, patients previously treated with three or four lines of therapy may enroll without regard to prior bevacizumab treatment. There is no exclusion for patients with baseline peripheral neuropathy. Patients may enroll without regard to NaPi2b expression; however, the role of the biomarker will be evaluated. The primary endpoint will be the objective response rate (ORR) in the high NaPi2b population and the secondary endpoints will be the ORR regardless of NaPi2b expression, as well as duration of response and safety.

"We believe this study design, which is an amendment to the ongoing Phase 1 expansion study, allows for significant operational efficiencies and leverages our current momentum in patient enrollment. The study design also allows us the opportunity to fully evaluate the role of the biomarker with endpoints in both the high NaPi2b and overall populations. We are excited to open this cohort to this heavily pretreated patient population with few options," said Arvin Yang, M.D., Ph.D., Senior Vice President and Chief Medical Officer of Mersana Therapeutics.

The single-arm registration strategy is an amendment to the ongoing multinational, multi-center, open label study protocol, and the Company expects to enroll approximately 100 patients with high NaPi2b expression and up to 180 patients overall.

On April 9, 2021 Nammi Therapeutics, Inc. (Nammi), an LA-based immunotherapy company, reported its first two cancer drug candidates, one from each of Nammi’s distinctive drug development platforms, Nammisomes and Masked ImmunoCytokines (MIC) (Press release, Nammi Therapeutics, APR 9, 2021, View Source [SID1234577806]). Nammi is presenting the lead products for each platform in two posters at the 2021 annual American Association for Cancer Research (AACR) (Free AACR Whitepaper) Conference. The posters will be available on the conference website April 10-June 21, 2021. The therapies being presented are selected products initiating GMP manufacturing and IND-enabling studies. Both of Nammi’s platforms embody our 3 core principles:

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The redundancy of immune regulatory pathways requires synergistic combinations for robust and broad efficacy of immuno-therapies in cancer;
Potent immune stimulators must be dampened while in circulation to avoid systemic toxicities; and
Optimal therapies will employ mechanisms to selectively deliver and activate immune cells within tumors to focus on killing the tumor rather than healthy tissue.
Nammi’s Nammisome platform combines immune modulating prodrugs into lipid nanoparticles enabling selective delivery to tumors. A second immunotherapy platform called Masked ImmunoCytokines (MICs) was acquired by a recent merger with Qwixel Therapeutics. MICs employ interferons, that have both direct anti-tumor cytotoxic activity as well as broad immune stimulating activity, and focus the potent effects by fusion to an anti-tumor targeting antibody and masking of the interferon so that it is only activated in the tumor microenvironment

QXL138AM: Poster #1726 highlights preclinical validation of our first in class MIC comprised of a CD138-targeted antibody fused with Interferon alpha (IFNα) that is masked with a tumor-selectively releasable peptide. CD138 is expressed in multiple myeloma as well as many different solid tumor indications including breast, colon, hepatic, ovarian, urothelial, and head and neck cancers.

NTI-55: Poster #1581 highlights preclinical validation of NTI-55, a novel combination of validated immune modulator lipid prodrugs, including a TLR7 agonist and an A2AR inhibitor, that stimulates an immune response and blocks an important tumor-derived immune checkpoint. These are broad based mechanisms that provide potential for NTI-55 in all solid tumor indications. These lipid prodrugs are assembled into lipid nanoparticles called Nammisomes that reduce systemic exposure to the immunotherapies while synchronizing delivery to, and activation at, the tumor sites.

"While strikingly distinct in design, the two approaches elegantly exemplify the vision of Nammi to develop immunotherapies that focus the immune system on anti-tumor activity while sparing patients from toxicities associated with systemic immune activation. We also believe there is a strong potential for synergy in combining the drugs to triangulate their immune activation for even more robust efficacy", said David Stover, Ph.D., President and CEO of Nammi.

Nammi has raised over $10M to date from Founders and Angel investors to drive preclinical development of both platforms. Nammi foresees filing INDs for both lead programs in mid-2022. Additional pipeline products, stemming from both the Nammisome and the MIC platforms, are in lead selection stage.

On April 9, 2021 Nimbus Therapeutics, a biotechnology company designing breakthrough medicines through structure-based drug discovery and development, reported the presentation of data from the company’s HPK1 inhibitor program in a poster at the AACR (Free AACR Whitepaper) Annual Meeting held virtually April 10-15, 2021 (Press release, Nimbus Therapeutics, APR 9, 2021, View Source [SID1234577755]).

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Newly disclosed data show that Nimbus’ small-molecule HPK1 inhibitor, NMBS-2, demonstrates significant tumor growth inhibition as a single agent and in combination with anti-PD1 in multiple mouse syngeneic tumor models. In combination with anti-PD1, NMBS-2 restored cytokine secretion from exhausted human T cells and induced robust tumor growth inhibition in the CT-26 model. Furthermore, animals treated with NMBS-2 and anti-PD1 showed complete rejection of subsequently reintroduced CT-26 tumor cells, suggesting the establishment of a robust and durable immune memory.

"Building on our promising findings to date demonstrating the anti-tumor immune activity of NMBS-2, these latest data provide a compelling picture of its potential clinical utility in a range of tumor types — both as a single agent and as a combination therapy with anti-PD1 treatment," said Peter Tummino, Ph.D., Chief Scientific Officer of Nimbus. "We’re rapidly progressing IND-enabling studies of NMBS-2 now with plans to initiate first-in-human studies in the second half of 2021."

On April 9, 2021 Kazia Therapeutics Limited (ASX: KZA; NASDAQ: KZIA), an Australian oncology-focused drug development company, reported to share new data from its ongoing phase II study of paxalisib in glioblastoma, the most common and most aggressive form of primary brain cancer (Press release, Kazia Therapeutics, APR 9, 2021, View Source [SID1234577773]).

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The data is the subject of a poster presentation at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, which is being held virtually from 10-15 April 2021, and from 17-21 May 2021.

Key Points

Pharmacokinetic (PK) data, which shows how long paxalisib remains in the human body, strongly supports 60mg once daily dosing, confirming planned administration schedule for commercial launch.

Analysis of food effect shows no significant difference between taking paxalisib with food versus on an empty stomach, allowing for a less restrictive administration schedule in commercial use.

Study remains ongoing, with a number of patients still in follow-up. Final data is now expected in 2H CY2021.

Kazia CEO, Dr James Garner, commented, "this is extremely useful and encouraging data, as we begin to compile regulatory documentation for paxalisib and give shape to its potential commercial approval. These results give us great confidence that we are administering the drug at the right dose, at the right frequency, and under the correct conditions. Moreover, the data helps to confirm the approach that we have taken in the GBM AGILE pivotal study."

He added, "a lot of our efforts at present are focused on assembling the complex package of scientific information that is required to secure FDA approval for any new drug. Today’s data provides one more piece in that jigsaw. More broadly, the phase II study is drawing to a conclusion, and we expect to be able to share final data in the second half of this year."

The poster can be viewed on the Company’s website at View Source

Background

The phase II study of paxalisib (NCT03522298) opened to recruitment in May 2018. It was designed to establish the most appropriate dose for use in newly-diagnosed patients, and to seek initial indications of potential clinical efficacy.

The study had previously determined a maximum tolerated dose (MTD) of 60mg, administered once daily. This determination was based primarily on safety findings, which suggested increased toxicity at a higher dose. Today’s PK data corroborates this finding, and shows that increased doses provide limited additional benefit in terms of drug exposure. In effect, these two independent variables both point to a dose of 60mg, giving a high degree of confidence that this is appropriate for future studies and for commercialisation.

Interim analyses of efficacy data from this study have previously shown encouraging signals of clinical efficacy, with a median overall survival (OS) of 17.5 months and a median progression-free survival (PFS) of 8.4 months reported at the most recent data cut. These figures compare very favourably to historical controls for temozolomide, which provide an OS of 12.7 months and a PFS of 5.3 months.

The phase II study remains ongoing, with a number of patients in follow-up, and is expected to deliver final data in 2H CY2021.

In January 2021, paxalisib opened to recruitment in the GBM AGILE pivotal study, which is expected to provide the basis for registration in the US and other territories.