On November 29, 2021 G1 Therapeutics, Inc. (Nasdaq: GTHX), a commercial-stage oncology company, reported that the Company has initiated a Phase 2, single arm, open-label study of trilaciclib administered prior to the antibody-drug conjugate (ADC), Trodelvy (sacituzumab govitecan-hziy) in patients with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC) (Press release, G1 Therapeutics, NOV 29, 2021, View Source [SID1234596203]). Antitumor efficacy and myeloprotective endpoints are being assessed in this trial. Initial results of this study are expected in the second half of 2022.

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"All of our clinical programs are designed to maximize the utility of trilaciclib and evaluate its ability to transform treatments for patients living with cancer, including potential synergies with newer promising agents, such as ADCs," said Raj Malik, M.D., Chief Medical Officer at G1 Therapeutics. "We are excited to develop this combination in TNBC, an area where trilaciclib in our Phase 2 trial and Trodelvy have both shown clinically meaningful and substantial improvements in overall survival and could act synergistically to improve patient outcomes with fewer myelosuppressive side effects. We believe strongly in the clinical rationale underlying this combination and that the data generated from this study will be instructive as we contemplate combinations of trilaciclib and ADCs in other treatment settings and tumor types."

Patient recruitment in this trial is now underway. Approximately 40 patients will be enrolled in this exploratory Phase 2, multicenter, open-label, single arm study evaluating the safety and efficacy of trilaciclib administered prior to sacituzumab govitecan-hziy in patients with unresectable, locally advanced or metastatic TNBC who received at least 2 prior treatments, at least 1 in the metastatic setting. Trilaciclib will be administered as a 30-minute IV infusion completed within 4 hours prior to the start of sacituzumab govitecan-hziy treatment on day 1 and day 8 of each 21-day cycle.

Study drug administration will continue until progressive disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or clinical progression as determined by the Investigator, unacceptable toxicity, withdrawal of consent, Investigator decision, or the end of the study, whichever occurs first.

The primary objective is to evaluate the anti-tumor efficacy of trilaciclib when administered prior to sacituzumab govitecan-hziy as measured by progression-free survival (PFS). Key secondary endpoints include evaluation of the anti-tumor efficacy as measured by the objective response rate (ORR), duration of objective response (DOR), clinical benefit rate (CBR), and overall survival (OS); and evaluation of the myeloprotective effects of trilaciclib.

About Triple Negative Breast Cancer (TNBC)

According to the American Cancer Society, nearly 300,000 new cases of invasive breast cancer are diagnosed annually in the U.S. Triple-negative breast cancer makes up approximately 15-20% of such diagnosed breast cancers. TNBC is cancer that tests negative for estrogen receptors, progesterone receptors, and excess HER2 protein. Because mTNBC cells lack key growth-signaling receptors, patients do not respond well to medications that block estrogen, progesterone, or HER2 receptors. Instead, treating mTNBC typically involves chemotherapy, radiation, and surgery. TNBC is considered to be more aggressive and have a poorer prognosis than other types of breast cancer. In general, survival rates tend to be lower with mTNBC compared to other forms of breast cancer, and mTNBC is also more likely than some other types of breast cancer to return after it has been treated, especially in the first few years after treatment. It also tends to be higher grade than other types of breast cancer.

On November 29, 2021 SpringWorks Therapeutics, Inc. (Nasdaq: SWTX), a clinical-stage biopharmaceutical company focused on developing life-changing medicines for patients with severe rare diseases and cancer, reported that it has achieved full enrollment in its Phase 2b ReNeu trial evaluating mirdametinib, an investigational MEK inhibitor, in adult and pediatric patients with NF1-associated plexiform neurofibromas (NF1-PN) (Press release, SpringWorks Therapeutics, NOV 29, 2021, View Source [SID1234596202]). The study enrolled over 50 adults and over 50 pediatric patients with NF1-PN. SpringWorks expects to provide an update on anticipated ReNeu trial timelines and milestones at an upcoming company-sponsored R&D Day.

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"Plexiform neurofibromas can cause severe disfigurement, pain, and functional impairment, and patients living with these devastating tumors are in need of new treatments. We are very pleased to have reached another important milestone on behalf of the NF1-PN patient community by completing enrollment in the ReNeu study," said Saqib Islam, Chief Executive Officer of SpringWorks. "We believe that mirdametinib has the potential to be a best-in-class treatment for NF1-PN based on its clinical activity, tolerability profile, ability to be taken without regard to food, and expected availability of a pediatric formulation. We look forward to providing further updates on the trial at our R&D Day."

The ReNeu trial is a multi-center, open-label Phase 2b trial evaluating the efficacy, safety, and tolerability of mirdametinib in patients two years of age and older with an inoperable NF1-associated PN causing significant morbidity. Patients receive mirdametinib at a dose of 2 mg/m2 twice daily (maximum dose of 4 mg twice daily) without regard to food. Mirdametinib is administered in a 3-week on, 1-week off dosing schedule. The primary endpoint of the ReNeu trial is objective response rate defined as ≥ 20% reduction in target tumor volume as measured by MRI and assessed by blinded independent central review. Secondary endpoints include safety and tolerability measures, duration of response, and changes from baseline in patient reported outcomes. More information about the ReNeu trial is available at www.clinicaltrials.gov under the identifier NCT03962543.

As previously disclosed, interim data from the first 20 adult patients enrolled in the ReNeu trial were presented at the 2021 Children’s Tumor Foundation NF Conference and showed encouraging efficacy and tolerability. As of the March 23, 2021 data cutoff date, 50% of patients had achieved an objective response as assessed by blinded independent central review, 80% remained on study, and median time on treatment was 13 cycles (approximately 12 months). Among these patients, mirdametinib was generally well tolerated, with the majority of treatment-related adverse events (TRAE) being Grade 1 or 2; only one Grade 3 TRAE and no Grade 4 or 5 adverse events (AE) were reported in these 20 patients.

About NF1-PN

Neurofibromatosis type 1 (NF1) is a rare genetic disorder that arises from mutations in the NF1 gene, which encodes for neurofibromin, a key suppressor of the MAPK pathway.1,2 NF1 is the most common form of neurofibromatosis, with an estimated global birth incidence of approximately 1 in 3,000 individuals, and approximately 100,000 patients living with NF1 in the United States.3,4 The clinical course of NF1 is heterogeneous and manifests in a variety of symptoms across numerous organ systems, including abnormal pigmentation, skeletal deformities, tumor growth and neurological complications, such as cognitive impairment.5 Patients with NF1 have an eight to 15-year mean reduction in their life expectancy compared to the general population.2

NF1 patients have approximately a 30-50% lifetime risk of developing plexiform neurofibromas, or PN, which are tumors that grow in an infiltrative pattern along the peripheral nerve sheath and that can cause severe disfigurement, pain and functional impairment; in rare cases, NF1-PN may be fatal.3,4,6 Patients with NF1 can also experience additional manifestations, including neurocognitive deficits and developmental delays.4 NF1-PNs are most often diagnosed in the first two decades of life.3 These tumors can be aggressive and are associated with clinically significant morbidities; typically, they grow more rapidly during childhood.7,8

Surgical removal of these tumors is challenging due to the infiltrative tumor growth pattern along nerves and can lead to permanent nerve damage and disfigurement.9 MEK inhibitors have emerged as a validated class of treatment for NF1-PN.4

About Mirdametinib

Mirdametinib is an oral, allosteric small molecule MEK inhibitor in development as a monotherapy treatment for neurofibromatosis type 1-associated plexiform neurofibromas (NF1-PN) and low-grade glioma (LGG), and as a combination therapy for the treatment of several subsets of biomarker-defined metastatic solid tumors. To date, over 250 subjects have been exposed to treatment with mirdametinib across clinical trials, with preliminary evidence of clinical activity against tumors driven by over-activated MAPK signaling.5

Mirdametinib is designed to inhibit MEK1 and MEK2, which occupy pivotal positions in the MAPK pathway. The MAPK pathway is a key signaling network that regulates cell growth and survival and that plays a central role in multiple oncology and rare disease indications when genetically altered.

The U.S. Food and Drug Administration (FDA) and the European Commission granted Orphan Drug designation for mirdametinib for the treatment of NF1, and the FDA granted Fast Track designation for the treatment of patients ≥ 2 years of age with NF1-PN that are progressing or causing significant morbidity.

On November 29, 2021 Ultragenyx Pharmaceutical Inc. (NASDAQ: RARE), a biopharmaceutical company focused on the development and commercialization of novel therapies for serious rare and ultra-rare genetic diseases, reported that Emil D. Kakkis, M.D., Ph.D., the company’s Chief Executive Officer and President, will present at the Evercore ISI 4th Annual HealthconX Conference on December 1, 2021 at 12:10 PM ET.

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The live and archived webcast of the presentation will be accessible from the company’s website at View Source The replay of the webcast will be available for 90 days.

On November 29, 2021 Northwest Biotherapeutics (OTCQB: NWBO) ("NW Bio"), a biotechnology company developing DCVax personalized immune therapies for solid tumor cancers, reported the closing of a $15 million financing on November 22, 2021, which brought the Company’s cash reserves above $20 million (Press release, Northwest Biotherapeutics, NOV 29, 2021, View Source [SID1234596198]).

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The Company plans to use the funding to help accelerate its activities related to its brain cancer program. The financing is in the form of a 22-month loan which requires no payments for 8 months, and then provides for a subsequent 14-month amortization period. The loan has a provision for prepayment, an annualized interest rate of 8% and OID of 10%. Upon announcement of the top line data ("TLD") from the Company’s Phase III clinical trial of DCVax-L for Glioblastoma brain cancer, the lender will have a then-springing right to exchange the outstanding balance of the loan for common shares priced at the price of the first private placement transaction following TLD less a 12% discount, and to purchase another 50% of that number of shares at the same price. This then-springing right expires 14 days after that post-TLD private placement.

On November 29, 2021 Fennec Pharmaceuticals Inc., a specialty pharmaceutical company, reported that it expects to receive a Complete Response Letter (CRL) after the PDUFA target action date of November 27, 2021 from the U.S. Food and Drug Administration (FDA) regarding its New Drug Application (NDA) for PEDMARKTM (a unique formulation of sodium thiosulfate), for intravenous administration for the prevention of ototoxicity associated with cisplatin chemotherapy in pediatric patients ≥1 month to 18 years of age with localized, non-metastatic, solid tumors (Press release, Fennec Pharmaceuticals, NOV 29, 2021, View Source [SID1234596197]).

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The FDA has indicated that, following a recent completion of a pre-approval inspection of the manufacturing facility of our drug product manufacturer, deficiencies have been identified. Once the official CRL is received, the Company plans to request a Type A meeting to discuss the deficiencies and steps required for the resubmission of the NDA for PEDMARKTM.

About PEDMARK (A unique formulation of sodium thiosulfate (STS))

Cisplatin and other platinum compounds are essential chemotherapeutic agents for many pediatric malignancies. Unfortunately, platinum-based therapies cause ototoxicity, or hearing loss, which is permanent, irreversible and is particularly harmful to the survivors of pediatric cancer.

In the U.S. and Europe, it is estimated that, annually, more than 10,000 children may receive platinum-based chemotherapy. The incidence of ototoxicity depends upon the dose and duration of chemotherapy, and many of these children require lifelong hearing aids. There is currently no established preventive agent for this type of hearing loss and only expensive, technically difficult, and sub-optimal cochlear (inner ear) implants have been shown to provide some benefit. Infants and young children that suffer ototoxicity at critical stages of development lack speech language development and literacy, and older children and adolescents lack social-emotional development and educational achievement.

PEDMARK has been studied by cooperative groups in two Phase 3 clinical studies of survival and reduction of ototoxicity, The Clinical Oncology Group Protocol ACCL0431 and SIOPEL 6. Both studies have been completed. The COG ACCL0431 protocol enrolled one of five childhood cancers typically treated with intensive cisplatin therapy for localized and disseminated disease, including newly diagnosed hepatoblastoma, germ cell tumor, osteosarcoma, neuroblastoma, and medulloblastoma. SIOPEL 6 enrolled only hepatoblastoma patients with localized tumors.

The Marketing Authorization Application (MAA) for sodium thiosulfate (tradename PEDMARQSI) is currently under evaluation by the European Medicines Agency (EMA). PEDMARK has received Breakthrough Therapy and Fast Track Designation by the FDA in March 2018.