On December 9, 2022, Puma Biotechnology, Inc. (the "Company") entered into a Securities Purchase Agreement (the "Purchase Agreement") with Alan H. Auerbach, the Company’s President, Chief Executive Officer and Chairman of the Board (the "Purchaser"). Pursuant to the Purchase Agreement, the Company agreed to sell 568,181 shares of its common stock, par value $0.0001 per share (the "Shares"), to the Purchaser for aggregate gross proceeds of approximately $2.5 million before deducting any offering expenses (the "Private Placement") (Filing, 8-K, Puma Biotechnology, DEC 9, 2022, View Source [SID1234625221]). The purchase price for each Share was $4.40, which was equal to the closing price of the Company’s common stock on NASDAQ on the date of the Purchase Agreement. The Private Placement closed on December 12, 2022.

The Private Placement is exempt from registration pursuant to the exemption for transactions by an issuer not involving any public offering under Section 4(a)(2) of the Securities Act of 1933, as amended (the "Securities Act"). The Shares were not registered under the Securities Act or any state securities laws and may not be reoffered or resold in the United States absent registration with the SEC or an applicable exemption from the registration requirements.

The foregoing description of the transaction does not purport to be a complete description of the Purchase Agreement and is qualified in its entirety by reference to the complete text of the Purchase Agreement, a copy of which is filed as Exhibit 10.1 to this Current Report on Form 8-K and is incorporated by reference herein.

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On December 9, 2022 Sermonix Pharmaceuticals Inc., a privately held biopharmaceutical company developing innovative targeted therapeutics to specifically treat ESR1-mutated metastatic breast and gynecological cancers, reported two poster presentations at the 2022 San Antonio Breast Cancer Symposium (SABCS) evaluating the results of an online survey of ER+/HER2- metastatic breast cancer (mBC) patients (Press release, Sermonix Pharmaceuticals, DEC 9, 2022, View Source [SID1234625144]). The survey’s objectives were to better understand this patient population’s knowledge of next-generation sequencing (NGS) and ESR1 mutations, and to learn about the group’s treatment goals and quality of life (QOL) concerns.

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The QOL-focused poster also received a GRASP Advocate Choice Award. GRASP, which stands for Guiding Researchers and Advocates to Scientific Partnerships, connects patient advocates with cancer researchers to make faster and more impactful progress to improve cancer treatments. The Sermonix poster will be discussed Dec. 15 during a post-SABCS virtual session.

Conducted in June 2022, the 42-question online EQUALS (ESR1 QUAlity of Life Survey) survey drew 474 respondents. Most respondents had some knowledge of NGS, but knowledge of ESR1 mutations was lower, and discordance between physician discussion of NGS and liquid biopsies was observed. Awareness of NGS and ESR1 mutations analyzed by demographics data also suggests socioeconomic disparities in patient education and knowledge.

Other key takeaways included that patients received medical information from medical sources as well as other mBC patients; that patients are nearly equally concerned about disease progression, qualify of life and treatment side effects; that disparities in quality of life and support at home exist based on ethnicity, age and income gaps; and that mBC advocacy groups can help reach ethnically diverse populations, which may help with clinical trial recruitment or disseminating patient education.

"The foremost concerns of ER+/HER2- metastatic breast cancer patients, as well as their understanding of the rapidly changing treatment and biomarker testing environment, has not been greatly studied, especially with respect to diverse populations," said Dr. Elizabeth Attias, Sermonix chief strategy and development officer, and a co-author of the SABCS posters. "As NGS testing becomes an increasingly important component of metastatic breast cancer treatment and the molecular patient journey, the EQUALS survey results underscore the need for further education on NGS and ESR1 mutations for all patients."

Noteworthy NGS/ESR1 mutation results:

Most patients’ oncologists (63%) had discussed tumor NGS by a blood test or tumor biopsy with them, but only 50% of them had explained liquid biopsy (assessment of circulating tumor DNA from a blood draw).
Patients knew a lot/moderate amount about NGS (65%), less so of liquid biopsies (57%).
When asked if they knew what an ESR1 mutation was, just 47% knew a lot/moderate amount; only 45% of patients thought they had been tested for an ESR1 mutation.
Noteworthy QOL results:

About half of patients (48%) reported good/very good QOL, with 22% reporting poor/very poor QOL. Common side effects mostly/moderately impacting QOL were: fatigue (54%), joint pain (50%), vaginal atrophy/dryness (47%) and vasomotor symptoms (46%).
Worry about disease progression occurred often: every day (26%), a few times a week (19%) or month (28%), or only before scans (18%).
Upon progression, patients worried slightly more about efficacy of new treatment (63%) and having additional options (58%) than they did about side effects (57%).
Patients’ current treatment goals were: control cancer growth/spread (69%), prolong life (68%), tolerate side effects (67%), maintain QOL (65%) and relieve suffering/pain (60%); similar to their goals at diagnosis.
Since diagnosis, major/moderate life impacts were: side effects (57%), mental health/stress (57%), QOL (54%), finances (45%) and inability to engage in activities (41%).
Most patients (60%) thought their mBC or treatment impacted their intimate/sexual relationship negatively and more than half (62%) worried about sexual intimacy. Only 39% of patients were comfortable discussing intimacy/sexual side effects with their medical team.
Most (91%) were concerned that their treatments may have a negative impact on their bones.
"The EQUALS Survey was able to illustrate the experiences of a remarkably diverse patient population thanks to the support of patient advocacy groups such as The Chrysalis Initiative and FORCE," said Kelly Shanahan, director at Metavivor Research and Support, Inc., and a co-author of the posters. "While that itself is a success, it is also important to note that all women in the survey report a high level of anxiety and stress regardless of color."

The EQUALS Steering Committee was comprised of Shanahan; Sarah Sammons, M.D., adjunct assistant professor in the Department of Medicine at Duke University and member of the Duke Cancer Institute; Jane Meisel, M.D., associate professor of hematology and medical oncology, and associate vice chair of faculty development and promotions at Winship Cancer Institute of Emory University; and Timothy Pluard, M.D., director of the Saint Luke’s Cancer Institute and the Koontz Center for Advanced Breast Cancer.

On December 9, 2022 Race Oncology Limited ("Race") is pleased to report that it has submitted a human ethics application to the Hunter New England Human Research Ethics Committee (NSW, Australia) seeking approval to commence the observational stage of a planned Phase 1/2b clinical trial of Zantrene (bisantrene dihydrochloride) in breast cancer patients to be treated with doxorubicin and cyclophosphamide and who have two or more cardiovascular risk factors (Press release, Race Oncology, DEC 9, 2022, View Source [SID1234625140]).

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This study will be led by Associate Professor Aaron Svedlov, a highly credentialed cardiologist with a research focus on cardio-oncology. Dr Sverdlov was awarded the 2018 Ministerial Award for Rising Stars in Cardiovascular Research. He established and cochairs the National Cardio-Oncology Working Group under the auspices of the Australian Cardiovascular Alliance. Dr Sverdlov has over 50 peer-reviewed publications and four book chapters in the field of cardio-oncology. The study will recruit and monitor up to 50 patients being treated for breast cancer using the standard of care (SoC) regimen of doxorubicin (Adriamycin) and cyclophosphamide-referred to as "AC chemotherapy".

The aim of this study is to identify the rate and level of heart damage caused by AC chemotherapy using modern advanced cardiac imaging and biochemical methods. In addition, the anti-cancer efficacy of AC chemotherapy will be monitored using a liquid biopsy (DNA) approach. The study is expected to fully recruit in 2023. The data from this study will be used to design a subsequent Phase 1/2b interventional trial that may help patients to avoid the permeant heart damage caused by AC chemotherapy and improve anti-cancer outcomes.

These human trials are fully funded from capital raised in December 2021 (ASX Announcement: 21 December 2021). Race CEO Phillip Lynch commented, "Cardioprotection remains a significant unmet patient need, and our preclinical data suggests that we have in Zantrene the opportunity to effectively address this need. I look forward to us progressing the clinical program and to clarifying the large commercial opportunity this program represents." Race Oncology Ltd ABN 61 149 318 749 Registered office: L36, 1 Macquarie Place, Sydney NSW 2000 www.raceoncology.com

Race CSO Dr Daniel Tillett commented, "This trial is Race’s first step in advancing the cardioprotection opportunity for Zantrene in the clinic. Gaining high quality observational data to design our interventional Phase 1/2b trial of Zantrene in breast cancer is critical to the success of this program. We look forward to updating our investors on the progress of this trial." Trial Background Anthracycline Chemotherapeutics Anthracyclines are one of the most effective anti-cancer treatments developed and are used in more cancer settings than any other class of chemotherapeutic agent.

1 These drugs are used to treat millions of cancer patients every year, including those with leukemias, lymphomas, neuroblastoma, kidney, liver, stomach, uterine, thyroid, ovarian, sarcomas, bladder, lung and breast cancers. The most clinically used anthracyclines are doxorubicin, daunorubicin, epirubicin and idarubicin.

2 The anti-cancer efficacy of anthracyclines is known to correlate to dose with higher doses providing greater efficacy, but at the expense of higher rates of serious and irreversible side-effects.1 In clinical practice, anthracycline chemotherapeutics such as doxorubicin are given at a level close to the patient’s maximal tolerated dose (MTD) in order to maximise the anticancer efficacy. Common dose limiting toxic side-effects of anthracyclines include: cardiotoxicity, suppression of the immune system and red blood cell production (myelosuppression), hair loss (alopecia), and gastrointestinal toxicity that can cause serious nausea and weight loss.1,2 Anthracycline Cardiotoxicity While highly effective anti-cancer drugs, the anthracyclines can cause serious and permanent damage to the heart in many patients. Some studies have estimated that over half of patients exposed to anthracyclines will develop some form of heart disease within 6 years of treatment.

3 Anthracyclines, such as doxorubicin and epirubicin (Figure 1), can lead to either acute or late onset cardiotoxicity. Acute toxicity is associated with increased inflammation and can lead to a pericarditis-myocarditis syndrome. Flaccid dilative cardiomyopathy is the predominant form of late onset anthracycline cardiotoxicity and can occur months to years after anthracycline exposure.

4 Figure 1. Chemical structures of the anthracyclines, doxorubicin and epirubicin. O OMe O OH OH O OH OH O O NH2 OH Me Doxorubicin O OMe O OH OH O OH OH O O NH2 OH Me Epirubicin Race Oncology Ltd ABN 61 149 318 749 Registered office: L36, 1 Macquarie Place, Sydney NSW 2000 www.raceoncology.com Although the mechanism of early and late onset anthracycline cardiotoxicity remains unclear, risk factors include increased cumulative anthracycline dose, concurrent mediastinal radiation, extremes of age, female gender, and pre-existing heart disease.

5 Prevention of Anthracycline Cardiotoxicity A number of potential cardioprotective techniques and therapies have been explored over the years, ranging from modified anthracycline preparations, anti-oxidants, free radical scavengers, renin-angiotensin-system antagonists, cardio-selective beta-blockers to statins. While many showed promise in animal studies, clinical studies have often had mixed results with many agents offering little or no cardio-protective benefit and/or compromising the cancer treatment.

6 None have offered the combined features of cardioprotection and improved anti-cancer efficacy. As a consequence, cardioprotective treatments are not routinely used in clinical oncology practice. Indeed, there remains clear demand for treatment options that prevent today’s cancer patient from becoming tomorrow’s cardiac patient, all while extending anti-cancer effect. Anthracycline use in Breast Cancer Breast cancer accounts for 30% of all new cancer diagnoses in women. It is estimated in the US that in 2022, 287,850 new cases of invasive breast cancer are expected to be diagnosed in women, along with 51,400 new cases of non-invasive (in situ) breast cancer.

7 The vast majority (94%) of new breast cancer patients present with early-stage disease.

8 Anthracycline agents such as doxorubicin and epirubicin, are routinely used for the management of breast cancer with follow-up taxane-based therapy. Surprisingly, women diagnosed with early-stage breast cancer were found to be more likely to die from cardiovascular disease than from breast cancer. Cardiovascular disease is also the leading cause of death in women over 75 diagnosed with stage II breast cancer.

9 The risk of cardiotoxic damage is so elevated in breast cancer patients that many oncologists have moved in recent years to using anthracycline-free treatment regimens or limiting patient dosages, despite the well-established efficacy of anthracyclines.9 Zantrene Cardioprotection Zantrene was originally developed as a heart safer alternative to the anthracyclines particularly with respect to preservation of heart muscle.10 In the late 1980s, Zantrene was the subject of a US based Phase 3 single agent clinical trial in advanced breast cancer patients.

This Phase 3 trial showed that Zantrene had comparable efficacy to standard of care treatment, doxorubicin, but was associated with significantly less damage to the patients’ hearts. Approximately 24% of patients who received doxorubicin suffered serious heart failure compared to just 6.6% with Zantrene.11 Race Oncology Ltd ABN 61 149 318 749 Registered office: L36, 1 Macquarie Place, Sydney NSW 2000 www.raceoncology.com In recent studies, Zantrene was found to protect human heart cardiomyocytes (heart muscle cells) grown in cell culture from doxorubicin-induced cell death (ASX Announcement: 22 November 2021). It was also found to protect the hearts of mice from the damaging effects of doxorubicin even when the chemotherapeutic dose was increased without significant additional toxicity or bone marrow suppression (ASX Announcement: 30 June 2022).

Cardioprotection Clinical Trial Design

This first study (Stage 1) is observational in nature and designed to assess the prevalence of cardiac toxicity (sub-clinical and clinical) in a cohort of cardiovascular high-risk breast cancer patients receiving doxorubicin/cyclophosphamide (AC) chemotherapy. Data from this study will be used to inform and power a subsequent interventional clinical trial (Stage 2) with the objective of using Zantrene in combination with AC to prevent cardiac damage and increase anti-cancer efficacy (Figure 2).

Figure 2. Two stage cardioprotection trial design. Stage 1 is an observational trial to determine the rate and level of cardiac damage from AC chemotherapy. Stage 2 is an interventional study where increasing levels of Zantrene are used to determine the optimal dose to minimise heart damage and provide anti-cancer efficacy. Cardiac damage rate & tumour response to AC treatment (50) ~20 ~20 ~20 ~20 Stage 1. Non-interventional Trial Stage 2. Active Treatment Trial Synthetic control arm Race Oncology Ltd ABN 61 149 318 749 Registered office: L36, 1 Macquarie Place, Sydney NSW 2000 www.raceoncology.com

Stage 1. Clinical Trial Summary

Study Title A non-interventional study to establish the incidence and extent of chemotherapy-induced cardiotoxicity in breast cancer patients at high cardiovascular risk receiving doxorubicin / cyclophosphamide (AC) therapy. Phase of Development Observational Active Ingredient Doxorubicin & cyclophosphamide Study Description Detection of chemotherapy induced cardiotoxicity in breast cancer patients. Principle Investigator A/Prof Aaron Svedlov Sponsor Race Oncology Indication/population ≥18 years of age with breast cancer and least 2 cardiac (per HFA-ICOS risk assessment score) risk factors who have been prescribed doxorubicin / cyclophosphamide chemotherapy for at least 4 cycles. Number of Subjects Up to 50 patients Study Period 24 months Study Design An observation study of the rate and extent of clinical and sub-clinical cardiac damage in breast cancer patients with multiple pre-existing cardiac risk factors as well as the cancer response rate. Statistical Methods Assuming a 15% cardiotoxicity rate (>11% decrease in global longitudinal strain by conventional echocardiographic measurements) 47 patients would be required using an alpha of 0.05 and power of 80%. End Points Primary: Incidence, severity and biomarkers of early, subclinical and clinical cardiotoxicity in breast cancer patients treated with AC chemotherapy. Secondary: Clinical safety profile of AC treatment in the patient population. Cancer response to AC treatment. Frequency, severity of alopecia (hair loss). Impact of AC treatment on overall patient quality of life. Participating Centres Calvary Mater Hospital, Newcastle, NSW. Race Oncology Ltd ABN 61 149 318 749 Registered office: L36, 1 Macquarie Place, Sydney NSW 2000 www.raceoncology.com

Q&A

Why study breast cancer patients getting standard of care doxorubicin / cyclophosphamide (AC) chemotherapy?

While the rate of clinical heart damage (>10% decrease in heart output) from AC chemotherapy is known from the scientific literature, the rate and level of sub-clinical heart damage has not been well described. Since sub-clinical heart damage has historically been considered an unavoidable aspect of chemotherapy, its rate and level have often not been collected at the level of precision required to construct a reliable synthetic control arm. In addition, new technology and imaging techniques now allow cardiac damage to be detected much more accurately and at lower levels than in the past. Knowing the true rate and level of chemotherapy induced heart damage will allow the interventional cardioprotective trial to be optimised, ensuring the minimum number of patients will be exposed to potentially ineffective doses of Zantrene. What are synthetic control arms? Synthetic control arms use real-world evidence to support interventional clinical trials. Instead of collecting clinical data from patients recruited for a trial who have been randomly assigned to a control or standard-of-care (SoC) arm, synthetic control arms model the experimental treatment controls using real-world data that has previously been collected from other sources such as health data generated during routine care, electronic health records, administrative claims data, disease registries, and/or other clinical trials12. Synthetic control arms may reduce or eliminate the need to enrol control or standard-ofcare participants in an active (interventional) trial, which can increase efficiency, reduce delays, lower trial costs, and speed the approval of life saving therapies. For example, if a trial needs to have 300 patients in the treatment arm in order to demonstrate the efficacy of a new drug, then instead of having to recruit 600 patients – 300 for the active arm and 300 for the control arm – only 300 patients may need to be recruited when using a synthetic control arm design. The major limitation of synthetic control arms is they require that the disease is predictable and that the standard of care is well-defined and stable. Fortunately, AC chemotherapy in breast cancer meets these two requirements. What are the advantages of this two-trial approach? By splitting the cardioprotection trial into two separate trials (observational and interventional) we can achieve the following outcomes: 1. The study can begin in Q1 2023 without the need for the new formulation to be manufactured and be ready for clinical trial. This will speed the time to completion of the full cardioprotection program. 2. The treatment cohort can be sized appropriately to ensure the minimum of patients are exposed to sub-optimal or excessive doses of Zantrene. Race Oncology Ltd ABN 61 149 318 749 Registered office: L36, 1 Macquarie Place, Sydney NSW 2000 www.raceoncology.com 3. Patients do not need to be randomly assigned to a placebo control arm in the Phase 1 interventional trial, increasing patient satisfaction and participation. 4. The cost of the trial is reduced as a separate observational study is cheaper to run than a conventional control arm in an interventional trial. How long will the human ethics approval process take? This is difficult to answer as it depends on many factors outside of Race’s control. Our expectation is that as this first observational study has minimal additional risks to the patients, it will receive approval relatively promptly allowing the trial to start in Q1 2023. When will the first patients be treated with Zantrene to protect their hearts during chemotherapy? The aim is to treat the first breast cancer patient with Zantrene soon after the new formulation has been manufactured and is ready for use in clinical trials – Race expects this to occur in Q3 2023 (ASX Announcement: 28 September 2022). References 1. Weiss RB. (1992) The anthracyclines: will we ever find a better doxorubicin? Semin Oncol. 9(6):670-86. 2. Venkatesh P, Kasi A. (2021) Anthracyclines. In: StatPearls. Treasure Island (FL): StatPearls Publishing. View Source 3. Swain SM, Whaley FS, Ewer MS. (2003) Congestive heart failure in patients treated with doxorubicin: a retrospective analysis of three trials. Cancer 97:2869–79. 4. Cai, F. et al. (2019) Anthracycline-induced cardiotoxicity in the chemotherapy treatment of breast cancer: Preventive strategies and treatment. Mol Clin Oncol 11, 15–23. 5. McGowan, J. V. et al. (2017) Anthracycline Chemotherapy and Cardiotoxicity. Cardiovascular drugs and therapy 31, 63–75. 6. Kimmick, G., Dent, S. & Klem, I. (2019) Risk of Cardiomyopathy in Breast Cancer: How Can We Attenuate the Risk of Heart Failure from Anthracyclines and Anti-HER2 Therapies? Curr Treat Options Cardiovasc Medicine 21, 30. 7. View Source 8. Waks AG, Winer EP. (2019) Breast cancer treatment: a review. JAMA. 321(3):288–300. 9. Ding, W. et al. (2018) Anthracycline versus nonanthracycline adjuvant therapy for early breast cancer: A systematic review and meta-analysis. Medicine 97, e12908. 10. Citarella, R. V. et al. (1982) Activity of a novel anthracenyl bishydrazone, 9,10-anthracenedicarboxyaldehydeBis[(4,5-dihydro-1H-imidazol-2-yl)hydrazone] dihydrochloride, against experimental tumors in mice. Cancer Res 42, 440–4. 11. Cowan, J. D. et al. (1991) Randomized Trial of Doxorubicin, Bisantrene, and Miltoxantrone in Advanced Breast Cancer: A Southwest Oncology Group Study. J National Cancer Inst 83, 1077–1084. 12. View Source

On December 9, 2022 Ambrx Biopharma Inc., or Ambrx, (NYSE: AMAM), a clinical stage biopharmaceutical company using its proprietary Engineered Precision Biologics (EPBs) platform to create antibody drug conjugates (ADCs), reported preliminary safety and efficacy data from its Phase 2 ACE‑Breast-03 study during a Spotlight Poster Presentation at the 2022 San Antonio Breast Cancer Symposium (SABCS) (Press release, Ambrx, DEC 9, 2022, View Source [SID1234625003]). The data presented by the investigator demonstrated 51.7% overall response rate (ORR) by RECIST v1.1 and 100% disease control rate (DCR) after treatment with ARX788 in HER2 positive mBC patients who are resistant or refractory to T-DM1.

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ACE-Breast-03 is a Phase 2, multicenter study of ARX788, an anti-HER2 ADC being evaluated for patients whose metastatic disease is resistant or refractory to T-DXd, T-DM1, or tucatinib-containing regimens. The study was conducted in the U.S., Korea, and Australia. As of the data cutoff, seven patients enrolled in the study were previously treated with T-DM1 and received a median of five lines of prior anticancer therapies. Four of seven patients were previously treated with HER2 tyrosine kinase inhibitors (TKIs). The median age was 59 years. The confirmed objective response rate (ORR) per RECIST v1.1 based was 57.1% (4/7). The disease control rate (DCR) was 100% (7/7) for patients treated with ARX788. Patients had a median time on therapy of 7.2 months and treatment remains ongoing. None of the patients experienced drug-related serious adverse events (SAEs) and all adverse events (AEs) were well tolerated with no treatment discontinuations from AEs.

Amplification of the human epidermal growth factor receptor 2 (HER2) gene with consequent HER2 protein overexpression occurs in approximately 20% of breast cancers (BC) and is a major driver of tumor development and progression. The HER2-targeted ADC trastuzumab emtansine (T-DM1) has been approved for the treatment of HER2-positive mBC after prior trastuzumab and taxane therapy. However, disease progression occurs in T-DM1 treated patients and as such, requires additional therapeutic options. The use of second-generation anti-HER2 ADCs using alternative molecules is being investigated to overcome drug resistance.

"This preliminary safety and efficacy data in a heavily pretreated population further reinforces our view of the stability and precision underlying Ambrx’s proprietary drug-linker and site-specific conjugation technology for ADC design," said Daniel O’Connor, Chief Executive Officer of Ambrx. "Our unique approach offers highly differentiated biologic design so that we can work towards providing better outcomes for patients with difficult-to-treat cancers."

Two Phase 3 studies and one registration enabled Phase 2 study with ARX788 (ACE-Breast-02, ACE-Gastric-02, and ACE-Breast-08) conducted by Amrbrx’s partner, NovoCodex Biopharmaceuticals, are ongoing in China with projected readouts in 2023.

Sara Hurvitz, M.D., Professor at David Geffen School of Medicine at UCLA, stated, "We are encouraged by the response rates and safety results, particularly given the significant need for new therapies among patients whose disease continues to progress after receiving multiple lines of therapy. We thank the San Antonio Breast Cancer Symposium for accepting our abstract as a Spotlight Poster Discussion presentation and the opportunity to show early results from the ACE-Breast-03 Phase 2 clinical trial."

Presentation highlights:

Presentation Title: ACE-Breast-03: Efficacy and safety of ARX788 in patients with HER2+ metastatic breast cancer previously treated with T-DM1
Presenting Author: Sara Hurvitz, M.D.
Poster Number: PD18-09
Key Highlights:

ARX788 provided clinical benefit to patients previously treated with T-DM1 who had disease progression
Patients treated with ARX788 had a confirmed ORR of 57.1% (4/7 patients) and unconfirmed ORR of 71.4% (5/7 patients)
The disease control rate was 100% (7/7 patients) for patients treated with ARX788
All adverse events were well tolerated with 85.7% of patients experiencing drug-related AEs (any grade) with 0% of AEs leading to discontinuation and 0% of patients experiencing drug-related SAEs
Treatment with ARX788 remains ongoing in this patient population with the median time of ARX788 therapy of 7.2 months
ARX788 is currently being studied in several registrational trials in breast cancer and gastric/GEJ cancer by Ambrx’s partner, NovoCodex Biopharmaceuticals, in China. Ambrx has recently paused the internal development of ARX788 and is seeking to partner ARX788 outside of China.

On December 9, 2022 Zymeworks Inc. (NYSE: ZYME), a clinical-stage biopharmaceutical company developing multifunctional biotherapeutics, reported new clinical data for zanidatamab, the company’s investigational HER2-targeted bispecific antibody, in combination with palbociclib, a CDK4/6 inhibitor, and fulvestrant, a selective estrogen receptor degrader, in patients with heavily pretreated HER2-positive hormone-receptor positive metastatic breast cancer (Press release, Zymeworks, DEC 9, 2022, View Source [SID1234625002]). The data were presented today in a spotlight poster session entitled Treatment of HER2-positive (HER2+) hormone-receptor positive (HR+) metastatic breast cancer (mBC) with the novel combination of zanidatamab, palbociclib, and fulvestrant during the San Antonio Breast Cancer Symposium (SABCS) taking place in San Antonio, Texas and virtually.

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Clinical Data Highlights

The data presented at SABCS are from a clinical study of 45 patients with heavily pretreated HER2-positive HR-positive metastatic breast cancer who received zanidatamab in combination with palbociclib and fulvestrant. Patients had received prior regimens containing HER2-targeted agents including trastuzumab (100%), pertuzumab (80%), T-DM1 (98%), and other available options.

In 36 efficacy-evaluable patients, treatment with zanidatamab in combination with palbociclib and fulvestrant resulted in a cORR of 33% and DCR of 92%, and the majority of patients experienced a decrease in tumor size. The mPFS was 9.6 months with seven patients still on study at the time of data cutoff (August 31, 2022). The regimen was generally well-tolerated, with the majority of treatment-related adverse events considered mild to moderate in severity (Grade 1 or 2).

"Zanidatamab together with palbociclib and fulvestrant shows encouraging antitumor activity and a manageable tolerability profile in patients with HER2‑positive hormone-receptor positive breast cancer that has progressed after treatment with multiple HER2-targeted agents," said Neil Josephson, M.D., Chief Medical Officer at Zymeworks. "We are encouraged by the durability of disease control and median progression-free survival in this heavily pretreated patient population indicating that this regimen has the potential to be developed as a chemotherapy-free treatment option for these patients."

The presentation is available to conference registrants on the SABCS conference website and is also available on the publications page of the Zymeworks website at View Source

Title: Treatment of HER2-positive (HER2+) hormone-receptor positive (HR+) metastatic breast cancer (mBC) with the novel combination of zanidatamab, palbociclib, and fulvestrant

Lead Author: Santiago Escrivá-de-Romani, MD, Vall d’Hebron Institute of Oncology (VHIO), Vall d’Hebron University Hospital; Barcelona, Spain

Program Number: PD18-10

About Zanidatamab

Zanidatamab is a bispecific antibody, based on Zymeworks’ Azymetric platform, that can simultaneously bind two non-overlapping epitopes of HER2, known as biparatopic binding. This unique design results in multiple mechanisms of action including dual HER2 signal blockade, increased binding and removal of HER2 protein from the cell surface, and potent effector function leading to encouraging antitumor activity in patients. Zymeworks is developing zanidatamab in multiple Phase 1, Phase 2 and pivotal clinical trials globally as a targeted treatment option for patients with solid tumors that express HER2. Zymeworks has entered into separate agreements with each of BeiGene, Ltd. (BeiGene) and Jazz Pharmaceuticals Ireland Limited (Jazz), granting each of BeiGene and Jazz with exclusive rights to develop and commercialize zanidatamab throughout various counties around world.