On January 15, 2021 Puma Biotechnology, Inc. (NASDAQ: PBYI), a biopharmaceutical company, reported interim results from the biliary tract cancers cohort of the ongoing SUMMIT trial of neratinib at the virtual 2021 Gastrointestinal Cancers Symposium hosted by the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) (ASCO GI) that is currently taking place (Press release, Puma Biotechnology, JAN 15, 2021, View Source [SID1234574061]). The presentation, entitled, "Targeting HER2 (ERBB2) mutation-positive advanced biliary tract cancers with neratinib: Results from the phase II SUMMIT "basket" trial," is being presented at a Poster Session by James J. Harding, MD, Regional Director, Early Drug Development, Memorial Sloan Kettering Cancer Center, an investigator of the trial. A copy of this poster presentation is available on the Puma website.

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The Phase II SUMMIT basket trial is an open-label, multicenter, multinational study that included a cohort evaluating the safety and efficacy of neratinib administered daily to patients who have HER2 (ERBB2) mutation-positive advanced biliary cancer. Patients received 240 mg of neratinib daily as a single agent.

In this cohort of 25 patients, 11 patients had cholangiocarcinoma, 10 patients had cancer of the gallbladder and 4 patients had cancer of the ampulla of Vater. 24 patients had received prior systemic chemotherapy with a median of 2 prior lines of therapy (range 0-7) before entering the trial.

The efficacy results from the trial demonstrated that there were 4 patients with confirmed partial responses (3 patients with cancer of the gallbladder and 1 patient with cholangiocarcinoma) and an additional 3 patients who had stable disease lasting ≥16 weeks (1 patient with cancer of the ampulla of Vater and 2 patients with cholangiocarcinoma, one of which remained on treatment for 56 weeks before progression). This resulted in an objective response rate of 16% and a clinical benefit rate of 28%. The durations of response were 3.0 months, 3.7 months, and 4.7 months and additionally one patient with gallbladder cancer remains on treatment >80 weeks.

The safety profile of patients with biliary tract tumors is similar to that previously reported for patients treated with neratinib monotherapy and mandatory loperamide prophylaxis in the first 2 months; treatment was manageable, with 56% of patients experiencing some diarrhea, including 24% with grade 3 diarrhea. There were no episodes of grade 4 diarrhea, and no treatment discontinuations due to diarrhea. Four patients required neratinib dose reduction and one patient was hospitalized due to diarrhea.

"We have shown neratinib to be safe and tolerable in these patients with advanced biliary tract tumors, and demonstrated activity comparable to current standards of care with similar progression-free survival and overall survival in these heavily pretreated patients," said Dr. Harding.

Alan H. Auerbach, CEO and President of Puma Biotechnology, added, "We are very pleased with the preliminary activity seen with neratinib in this cohort of patients and specifically in patients with cancer of the gallbladder and cholangiocarcinoma."

On January 15, 2021 CytRx Corporation (OTCQB:CYTR) ("CytRx" or the "Company"), a specialized biopharmaceutical company focused on research and development for the oncology and neurodegenerative disease categories, highlighted that NantKwest, Inc. (NASDAQ: NK) ("NantKwest") and ImmunityBio, Inc. ("ImmunityBio") reported that their ongoing Phase 2 clinical trials of a novel combination immunotherapy – which include CytRx’s licensed drug aldoxorubicin – for locally advanced or metastatic pancreatic cancer have produced early indications of increased survival rates for patients with no other approved treatment options (Press release, CytRx, JAN 15, 2021, View Source [SID1234574060]). Interim results of the three-cohort trials, known as QUILT 88, show median survival rates more than doubled that of the historic rate in patients with advanced metastatic pancreatic cancer (for which no other FDA approved treatment exists).

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According to NantKwest and ImmunityBio, the current trials were based on the original Cancer Moonshot hypothesis and exploratory QUILT trials initiated in 2017. The companies announced this week that the trials appear to validate the theory that by orchestrating natural killer and T-cell therapy, survival rates for individuals afflicted with advanced metastatic pancreatic cancer could be improved without high-dose chemotherapy. The interim trial results disclosed by the companies are as follows:

In the Cancer Moonshot QUILT trials of haNK combined with PD-L1 inhibitor avelumab, which were completed in 2019, the median overall survival rate more than doubled (three months historic control versus 8 months in the treatment arm) in the 12-patient trial.
A complete remission was achieved when replacing haNK and PD-L1 inhibitor avelumab with PD-L1 t-haNK and four out of five patients who had not yet reached median survival time (three months) are alive 8-16 months since beginning treatment on these expanded protocols.
A single-arm Phase 2 trial (QUILT 88, Cohort C) was initiated in October 2020, for which the primary endpoint is overall survival and 15 out of 18 (83%) patients enrolled with second-line or greater pancreatic cancer remain alive to date.
Randomized Phase 2 trials (QUILT 88, Cohorts A and B) for first- and second-line metastatic pancreatic cancer are actively enrolling at three sites with more than 50 patients enrolled or being evaluated in QUILT 88 to date.
Additional information pertaining to QUILT 88 trial details:

According to NantKwest and ImmunityBio, QUILT 88 is intended to evaluate the comparative efficacy and overall safety of standard-of-care chemotherapy versus standard-of-care chemotherapy in combination with PD-L1 t-haNK, Anktiva (N-803) and aldoxorubicin in subjects with locally advanced or metastatic pancreatic cancer. Each treatment setting, as well as each first- and second-line or later maintenance treatment, will be evaluated independently as Cohort A, Cohort B, and Cohort C, respectively, with A and B having independent experimental and control arms. The trial will initially enroll 298 subjects across all three cohorts. The primary objective of Cohorts A and B is progression-free survival and the objective of Cohort C is overall survival per RECIST V1.1. Secondary objectives include initial safety and additional efficacy measures, including overall response rate, complete response rate, durability of response, disease control rate, and overall survival.

Cancer Moonshot QUILT trial numbers include QUILT 3.039, 3.060, 3.070, and 3.080.

Additional information pertaining to QUILT 88 trial sites and enrollment:

According to NantKwest and ImmunityBio, there are currently three trial sites that have been activated: Hoag Memorial Hospital Presbyterian in Orange County, Calif.; The Chan Soon-Shiong Institute for Medicine in Los Angeles County, Calif.; and Avera McKennan Hospital and University Health Center in Sioux Falls, South Dakota. The latter site will serve patients in the tri-state area (Iowa, Nebraska, and South Dakota). More than 50 patients are currently enrolled in or being evaluated for the trial.

Additional information pertaining to pancreatic cancer:

Pancreatic cancer is the fourth leading cause of cancer-related deaths in the U.S., with an estimated 47,050 deaths and 57,600 new cases expected in 2020. It is the 12th most common cancer worldwide, with around 338,000 new cases diagnosed in 2012 (2% of all cancer diagnoses). Pancreatic cancer continues to increase today with no standard of care available for patients beyond second line. A clear unmet medical need exists in these patients facing anticipated survival times that are brief and high levels of existing comorbidities.

Patrick Soon-Shiong, M.D., Chairman, and Chief Executive Officer of ImmunityBio, issued the following statements earlier this week:

"For five patients for whom no other treatment was available, we replaced haNK and avelumab with the investigational NK cell therapy PD-L1 t-haNK and were pleased to observe a complete remission in the first patient to receive this combo therapeutic. To date, four out of five of these patients remain alive since beginning treatment. These observations confirmed the promise of our hypothesis that activating the patient’s own immune system with low-dose chemo immunomodulation therapy could improve outcomes. On the basis of our initial studies, we initiated our QUILT 88 randomized trials in metastatic pancreatic cancer and are pleased to present today those findings, including Cohort C survival rates. While this data is still early, a doubling of the survival rate is encouraging and warrants further confirmation through QUILT 88."

Steven A. Kriegsman, CytRx’s Chairman and Chief Executive Officer, commented:

"We are very encouraged to see that Aldoxorubicin is helping to deliver positive outcomes for pancreatic cancer patients participating in the ongoing QUILT 88 trials. In our view, the interim results announced by NantKwest and ImmunityBio reflect the significant potential of the novel combination immunotherapy being studied. We look forward to monitoring the continuation of QUILT 88 and remain optimistic about the role Aldoxorubicin can play in combating aggressive cancers."

On January 15, 2021 AVEO Oncology (Nasdaq: AVEO) reported the presentation of results from the Phase 1b portion of the Phase 1b/2 DEDUCTIVE clinical trial of tivozanib (FOTIVDA), AVEO’s vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI) drug candidate, in combination with IMFINZI (durvalumab), AstraZeneca’s (LSE/STO/Nasdaq: AZN) human monoclonal antibody directed against programmed death-ligand 1 (PD-L1), in patients with advanced or metastatic hepatocellular carcinoma (HCC) (Press release, AVEO, JAN 15, 2021, View Source [SID1234574059]). The results are being presented today in a poster session at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal (ASCO GI) Cancers Symposium being held virtually.

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A total of seven patients with advanced or metastatic HCC were enrolled in the Phase 1b portion of the study, which was designed to determine the recommended Phase 2 dose and assess preliminary safety and efficacy of the tivozanib/durvalumab combination. Patients received 1.0 mg of tivozanib for 21 days followed by 7 days off therapy combined with 1500 mg of durvalumab every 28 days. The combination was well tolerated, with no dose-limiting toxicities. The combination demonstrated a 29% partial response (PR) rate and 71% disease control rate (PR + stable disease). Completion of enrollment in the ongoing Phase 2 portion of the study, which is expected to enroll up to an additional 30 subjects, is anticipated later this year.

"With a five-year survival rate of less than 5%, advanced or metastatic HCC represents an area of high unmet need," said Renuka Iyer, M.D., Professor of Oncology and Co-Director, Liver and Pancreas Tumor Center, Roswell Park Comprehensive Cancer Center. "These data demonstrated the tolerability of the tivozanib and immunotherapy combination, and I look forward to its further evaluation in the Phase 2 portion of the study."

"We believe that data observed in the Phase 1b portion of the DEDUCTIVE study continue to support tivozanib’s potential to serve as an attractive VEGFR TKI to use in the immunotherapy combination setting," said Michael Bailey, president and chief executive officer of AVEO. "As we await a decision on our New Drug Application for single agent tivozanib in relapsed or refractory renal cell carcinoma (RCC), we remain focused on executing on our combination strategy, including in metastatic RCC and HCC."

About Tivozanib (FOTIVDA)

Tivozanib is an oral, once-daily, next-generation VEGFR TKI discovered by Kyowa Kirin Co. and approved as FOTIVDA for the treatment of adult patients with advanced RCC in the European Union and other countries in the territory of the Company’s partner, EUSA Pharma (UK) Limited (EUSA territory). It is a potent, selective and long half-life inhibitor of all three VEGF receptors and is designed to optimize VEGF blockade while minimizing off-target toxicities, potentially resulting in improved efficacy and minimal dose modifications.1,2 Tivozanib is being studied in the TIVO-3 trial, which is supporting a regulatory submission of tivozanib in the U.S. seeking marketing approval as a treatment for adult patients with relapsed or refractory advanced RCC. Tivozanib has been shown to significantly reduce regulatory T-cell production in preclinical models3 and has demonstrated synergy in combination with nivolumab (anti PD-1) in a Phase 2 study in RCC.4 Tivozanib has been investigated in several tumor types, including renal cell, hepatocellular, colorectal, ovarian and breast cancers. Tivozanib is also being studied by partner Kyowa Kirin Co. in non-oncology indications.

On January 15, 2021 NANOBIOTIX (Paris:NANO) (NASDAQ:NBTX) (Euronext: NANO – NASDAQ: NBTX – the ‘‘Company"), a clinical-stage biotechnology company focused on developing first-in-class product candidates that use proprietary nanotechnology to transform cancer treatment, reported positive first results from the complete phase Ib part of a phase Ib/II study evaluating NBTXR3 (PEP503) activated by radiotherapy with concurrent chemotherapy (Press release, Nanobiotix, JAN 15, 2021, View Source [SID1234574058]). This study is sponsored and administered by PharmaEngine, Inc. in Taiwan pursuant to a License and Collaboration agreement with the Company. The data were presented at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium (ASCO-GI 2021).

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A NEW RADIOENHANCER, PEP503 (NBXTR3), IN COMBINATION WITH CONCURRENT CHEMORDIATION IN LOCALLY ADVANCED OR UNRESECTABLE RECTAL CANCER: THE DOSE-FINDING PART OF A PHASE IB/II TRIAL
Authors: Jaw-Yuan Wang, Ching-Wen Huang, Ming-Yii Huang, Huang-Ming Hu, Wen-Hung Hsu, Hsiang-Yao Shih, Chiao-Yun Chen, Chou-Pin Chen, Jeffrey Yung-Chuan Chao, You-Hsin Chiu

Abstract Number: 66

Background

Radiotherapy, chemotherapy and surgery are elements of the standard of care for patients with rectal cancer. Concurrent chemoradiation (CCRT) followed by surgery, if possible, is the recommended option for patients with resectable (surgically removable) T3 to T4 tumors, or who have locally unresectable or inoperable disease. Better response to CCRT, prior to surgery, may be associated with better long-term treatment outcomes.

The potential efficacy of tumor-agnostic NBTXR3 in increasing tumor shrinkage—as observed in phase I head and neck cancer, and phase I liver cancer studies—may result in tumor downstaging and lead to an improvement in surgical outcomes.

Study Design

The complete dose-finding part of this phase Ib/II study evaluated the safety, feasibility and recommended phase II dose of NBTXR3 for patients with locally advanced (T3 to T4) or unresectable rectal cancer. The study enrolled 20 patients: with seven, four, three, and six patients at the 5%, 10%, 15%, and 22% dose levels, respectively.

Topline Results

Intratumoral injection of NBTXR3 with CCRT was feasible and the product candidate was well tolerated at all dose levels, and no adverse events (AEs) or serious adverse events (SAEs) associated with NBTXR3 were observed in the study. One dose-limiting toxicity associated with the injection procedure was observed (urinary tract infection). The most frequently reported AEs were diarrhea (approximately 45%), leukopenia (approximately 40%), and dermatitis (approximately 25%), however all were grade one or grade two.

More than 70% of patients in the study showed objective tumor response after CCRT. Around 90% of patients underwent total mesorectal excision (surgery); and 17.6% achieved pathological complete response (pCR). 50% of patients receiving surgery in the study had good tumor regression (tumor regression grade 0 or 1 according to modified Ryan scheme).

The RP2D has been defined as 22% of tumor volume and the extension phase II is ongoing in Taiwan.

About NBTXR3
NBTXR3 is a novel, potentially first-in-class product candidate designed to destroy tumors through physical cell death when activated by radiotherapy. NBTXR3 has a high degree of biocompatibility, requires one single administration before the first radiotherapy treatment session, and has the ability to fit into current worldwide standards of radiation care. The physical mode of action of NBTXR3 makes it applicable across solid tumors such as lung, prostate, liver, glioblastoma, and breast cancers.

On January 15, 2021 Affimed N.V. ("Affimed" or the "Company") (Nasdaq: AFMD), a clinical stage immuno-oncology company committed to giving patients back their innate ability to fight cancer, reported the closing of its previously announced public offering of 16,666,667 common shares, at the public offering price of $6.00 per share, and the exercise in full by the underwriters of their option to purchase an additional 2,500,000 common shares (Press release, Affimed, JAN 15, 2021, View Source,16%2C666%2C667%20common%20shares%2C%20at%20the [SID1234574057]). The exercise of the option to purchase over-allotment shares brought the total number of common shares sold by Affimed to 19,166,667 common shares and increased the gross proceeds raised in the offering, before deducting underwriting discounts and commissions and estimated expenses of the offering payable by Affimed, to $115 million.

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Jefferies LLC, SVB Leerink LLC and Credit Suisse Securities (USA) LLC are acting as joint book-running managers and Laidlaw & Company (UK) Ltd. is acting as co-manager. A shelf registration statement relating to these securities filed with the Securities and Exchange Commission (the "SEC") was declared effective by the SEC on December 30, 2020. The offering was made only by means of a prospectus and prospectus supplement. A prospectus supplement and accompanying prospectus related to the offering have been filed with the SEC and are available at the SEC’s website located at www.sec.gov. Copies of the prospectus supplement and accompanying prospectus related to the offering may be obtained by contacting Jefferies LLC, Attention: Equity Syndicate Prospectus Department, 520 Madison Avenue, 2nd Floor, New York, NY 10022, or by telephone at (877) 821-7388 or by email at [email protected], SVB Leerink LLC, Attention: Syndicate Department, One Federal Street, 37th Floor, Boston, MA 02110, by telephone at (800) 808-7525 ext. 6132, or by email at [email protected], or Credit Suisse Securities (USA) LLC, Attention: Prospectus Department, 6933 Louis Stephens Drive, Morrisville, NC 27560, by telephone at (800) 221-1037, or by email at [email protected]

This press release shall not constitute an offer to sell or a solicitation of an offer to buy, nor shall there be any sale of, these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.