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Constellation Pharmaceuticals Presents Phase 1 Data for CPI-0209 at ASCO Annual Meeting

On June 4, 2021 Constellation Pharmaceuticals, Inc. (Nasdaq: CNST), a clinical-stage biopharmaceutical company using its expertise in epigenetics to discover and develop novel therapeutics, reported in a poster presentation preliminary data from the ongoing Phase 1/2 trial of CPI-0209, a novel, second-generation, small molecule inhibitor of Enhancer of Zeste Homolog 2 (EZH2) (Press release, Constellation Pharmaceuticals, JUN 4, 2021, View Source [SID1234583530]). These data were published online in conjunction with the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, and show comprehensive target engagement and durable exposure of CPI-0209. Anti-tumor activity of CPI-0209 in pre-clinical models was demonstrated across several advanced hematologic and solid tumor types.

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"We designed CPI-0209 to improve on first-generation EZH2 inhibitors in a number of ways, including increased potency, long residence time on target, and a lack of auto-induction of metabolism. These enhancements translate in the clinic, which we believe will be key to unlocking the full therapeutic potential of EZH2 inhibition," said Jigar Raythatha, president and chief executive officer of Constellation Pharmaceuticals. "I am also pleased that dosing is under way in our Phase 2 expansion cohorts at the selected dose."

Preliminary Data Highlights

A total of 40 patients were treated across 14 tumor types.
A 350mg oral, once-daily dose of CPI-0209 has been selected for evaluation in Phase 2.
As of the data cut of March 9, 2021, of the 4 BAP1 loss mesothelioma patients, 1 patient had a durable partial response (PR) after four cycles of treatment and 2 had stable disease (SD). Subsequently, to the data cut, the fourth patient also had SD.
High levels of target engagement observed preclinically are now corroborated clinically.
Safety

A total of 40 patients were evaluated for safety. CPI-0209 was generally well tolerated, with a manageable adverse event profile. Across all dose cohorts, 43% of patients had at least one Grade 3 or greater treatment emergent adverse event (TEAE), 28% of patients had at least one serious adverse event (SAE). The most common TEAEs (≥ 15%) included thrombocytopenia (reversible and dose dependent), diarrhea, asthenic conditions, nausea, anemia, dysgeusia, abdominal pain and alopecia. 23% of patients reported a TEAE that led to dose reduction or interruption. Four patients discontinued treatment because of TEAEs. One patient in the highest dose cohort (375mg) experienced Grade 4 thrombocytopenia, and one patient experienced a Grade 5 adverse event due to progressive disease.

For further details, please view the ASCO (Free ASCO Whitepaper) poster.

ASCO Poster Presentation

TITLE: Phase 1/2 First-in-Human Study of CPI-0209, a Novel Small Molecule Inhibitor of Enhancer of Zeste Homolog 2 (EZH2) in Patients with Advanced Tumors (Abstract Code 3104)

About CPI-0209

CPI-0209 is a second-generation EZH2 inhibitor designed to achieve comprehensive target coverage through extended on-target residence time and enhanced potency compared with first-generation EZH2 inhibitors. These features lead to faster onset and a more comprehensive on-target action than first-generation EZH2 inhibitors, as well as robust anti-tumor activity in models of multiple hematologic and solid cancer types.

About CPI-0209 clinical trial

The Phase 1 portion of the CPI-0209 Phase1/2 clinical trial is an open label, dose escalation study in patients with advanced tumors. A total of 41 patients were enrolled, of which 40 patients received CPI-0209. The primary objective of the Phase 1 portion is to evaluate safety and determine the recommended Phase 2 dose of CPI-0209.

The Phase 2 portion is an open label, single arm study, currently enrolling 20 to 29 patients per cohort in the following tumor types: relapsed urothelial carcinoma, relapsed ovarian clear cell carcinoma, and relapsed endometrial carcinoma all with known ARID1A mutation; relapsed or refractory lymphomas; malignant pleural or peritoneal mesothelioma with known BAP1 loss; as well as metastatic castration-resistant prostate cancer. The goal of these cohorts is to establish the safety and the antitumor activity of CPI-0209 as a monotherapy for patients with these tumor types.

Roche presents data on giredestrant, a next generation selective oestrogen receptor degrader for people with hormone receptor-positive, HER-2 negative breast cancer

On June 4, 2021 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported the presentation of new and updated data on giredestrant (formerly known as GDC-9545), an investigational next generation oral selective oestrogen receptor degrader (SERD), in people with hormone receptor (HR)-positive, HER2-negative breast cancer (Press release, Hoffmann-La Roche, JUN 4, 2021, View Source [SID1234583529]). Breast cancer is now the most common cancer in the world, with HR-positive being the most common subtype representing 70% of cases.1,2 Data from these studies will be presented at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, which will be held June 4-8, 2021.

"We’re encouraged by the results of these ongoing giredestrant studies which form part of a comprehensive clinical development programme in HR-positive breast cancer," said Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development. "Prolonged treatment durations and risk of relapse can represent significant challenges for patients, therefore a need remains for more effective and tolerable treatment options."

The data from two phase I studies presented at ASCO (Free ASCO Whitepaper) show giredestrant’s promising clinical activity and safety profile in HR-positive, HER2-negative breast cancer:

NCT03916744: Interim analysis of this window of opportunity study in the post-menopausal, neoadjuvant (preoperative) setting showed giredestrant’s consistent and compelling activity.3

The pharmacodynamic effect of giredestrant was assessed using the Ki67 proliferation biomarker, which indicates the ability of a therapy to suppress tumour growth.
Giredestrant showed promising impact on tumour cell proliferation after ~14 days of treatment; a mean reduction of Ki67 of 78% (95% CI:72-83); 55% of tumours exhibited complete cell cycle arrest defined as Ki67 ≤2.7%.
The safety profile of giredestrant in the neoadjuvant setting was consistent with its mechanism of action and there were no discontinuations due to adverse events (AEs).

NCT03332797: Updated data from this phase I study in the locally advanced/metastatic breast cancer setting showed that giredestrant as a monotherapy was well-tolerated, and had promising clinical activity, irrespective of the type of prior therapy or the presence of ESR1 mutations (mutations in the ESR1 gene are important mechanisms of resistance to hormone therapy).4,5

At 30mg, a 20% overall response rate was seen in patients with measurable disease at baseline, and clinical benefit rates of 55% and 76% were observed in the overall and ESR1 mutant subgroups, respectively.
Giredestrant showed notable activity in the ESR1 mutant subgroup indicating that giredestrant overcomes ESR1 mutations.
Giredestrant was well-tolerated at all doses (10–250mg); there were no dose limiting toxicities with giredestrant monotherapy; AEs were generally low grade.
A standardised once-daily 30mg dose has been selected for the giredestrant development programme, both as a monotherapy and in combination studies.

We are currently enrolling patients into two phase II studies (CoopERA and AcelERA) evaluating giredestrant in neoadjuvant oestrogen receptor (ER)-positive early breast cancer, and previously treated locally advanced or metastatic breast cancer respectively, as well as one phase III study (PersevERA), evaluating giredestrant plus palbociclib against letrozole plus palbociclib in patients with ER-positive, HER2-negative locally advanced or metastatic breast cancer.6,7,8

The mainstay of treatment is to block oestrogen, but the side effects of this have a very significant impact on quality of life and can greatly affect treatment adherence.9,10 With giredestrant, we are striving to provide a more tailored, more effective and less debilitating treatment for HR-positive breast cancer.

Giredestrant received U.S. Food and Drug Administration (FDA) Fast Track Designation (FTD) for ER-positive, HER2-negative, second and third-line metastatic breast cancer on 15 December 2020. A FTD is a process designed to facilitate the development, and expedite the review of drugs to treat serious conditions and fill an unmet medical need.11

About giredestrant
Giredestrant is a next generation investigational SERD, designed to fully block ER signalling with robust receptor occupancy. Oestrogen encourages HR-positive breast cancer cells to grow by attaching to the ER. Giredestrant works by blocking this receptor to prevent the action of oestrogen, and in the process causes the receptor to be degraded. This investigational medicine has also shown efficacy regardless of ESR1 mutation status (mutations in the ESR1 gene are important mechanisms of resistance to hormone therapy).5,9,12,13

Orally given, giredestrant delivers a strong clinical efficacy and safety profile and has shown superior pre-clinical potency over other SERDs in development.12,14 The oral administration of giredestrant has the potential to transform the treatment experience for patients, offering greater convenience and a less painful option compared to therapies administered via intramuscular injection.

Giredestrant has a comprehensive development programme across a broad range of settings and treatment combinations for patients with HR-positive, HER2-negative breast cancer. A standardised once-daily 30mg dose has been selected for the giredestrant development programme, both as a monotherapy and in combination studies.

About NCT0391674415
An open-label, short-term window study due to explore the safety, pharmacokinetics, pharmacodynamics, and activity of giredestrant in around 75 post-menopausal women with untreated stage I-III ER-positive/HER2-negative early breast cancer. The primary endpoint of the study will be the change in Ki67 scores (a measure of how quickly cancer cells are proliferating) between biopsies taken before and after treatment. Secondary endpoints include safety outcomes and plasma concentration of giredestrant.

About NCT0333279716
An ongoing phase Ia/b first-in-human, multi-centre, open-label, dose escalation, dose expansion study. The study is exploring the safety, pharmacokinetics, pharmacodynamics, and activity of giredestrant as a single agent, and in combination with palbociclib and/or luteinizing hormone-releasing hormone agonist, in 181 people with locally advanced or metastatic ER-positive/HER2-negative breast cancer. Primary endpoints of the study include the maximum tolerated dose of giredestrant and as well as safety outcomes. Secondary endpoints include plasma concentration levels of giredestrant and palbociclib over time, objective response rate, clinical benefit rate and duration of response.

Spectrum Pharmaceuticals Presents Poziotinib Data in Patients with Brain Metastases from the ZENITH20 Clinical Trial at 2021 ASCO Annual Meeting

On June 4, 2021 Spectrum Pharmaceuticals (NasdaqGS: SPPI), a biopharmaceutical company focused on novel and targeted oncology therapies, reported an e-poster on poziotinib CNS activity in patients with NSCLC with EGFR or HER2 exon 20 mutations (Press release, Spectrum Pharmaceuticals, JUN 4, 2021, View Source [SID1234583528]). These data from Cohorts 1, 2 and 3 of the ongoing ZENITH20 clinical trial assessed the results from 36 patients with brain metastases at baseline with three patients (8%) achieving intracranial complete responses. The presentation titled "CNS activity of poziotinib in NSCLC with exon 20 insertion mutations" is available on the website for the 2021 ASCO (Free ASCO Whitepaper) Annual Meeting being held June 4-8, 2021.

"CNS metastases are a common and life-threatening complication of metastatic disease in NSCLC patients," said Francois Lebel, M.D., Chief Medical Officer of Spectrum Pharmaceuticals. "These data show clinically meaningful CNS activity for poziotinib treated NSCLC patients with CNS metastases with EGFR or HER2 exon 20 insertion mutations."

CNS Activity from the ZENITH20 Clinical Trial

The ZENITH20 trial has enrolled NSCLC patients with EGFR and HER2 exon 20 insertion mutations. This analysis looked at the results for 284 patients from Cohorts 1, 2 and 3. 36 patients had brain metastases as reviewed by an independent central imaging laboratory from baseline. Brain metastasis occurs frequently in NSCLC, up to 25% of patients, and is associated with short survival. Patients received poziotinib at a dose of 16mg once daily.

The poster presentations will be available for viewing by registered participants during the conference via the ASCO (Free ASCO Whitepaper) website beginning on June 4, 2021.

Heat Biologics to Showcase Favorable Survival Data of HS-110 in Previously Treated Non-Small Cell Lung Cancer Patients at 2021 American Society of Clinical Oncology Annual Meeting

On June 4, 2021 Heat Biologics, Inc. (Nasdaq: HTBX), a clinical-stage biopharmaceutical company focused on developing first-in-class therapies to modulate the immune system, reported that Dr. Roger B. Cohen, MD, Professor of Medicine at the University of Pennsylvania Perelman School of Medicine, presented an overview of the latest HS-110 data at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting which is being held from June 4-8, 2021 (Press release, Heat Biologics, JUN 4, 2021, View Source [SID1234583527]). This poster presentation can be viewed on Heat Biologics’ website at: View Source The ASCO (Free ASCO Whitepaper) Annual Meeting is the world’s largest oncology conference showcasing the latest advancements in cancer research.

HS-110, in combination with a checkpoint inhibitor (CPI), is a potentially transformational agent to improve survival benefit for patients with non-small cell lung cancer (NSCLC). This is a first-in-class, allogeneic, off-the shelf cell-based therapy developed by Heat leveraging its proprietary gp96 platform. At this year’s ASCO (Free ASCO Whitepaper) meeting, the Company is pleased to report the latest data of HS-110 in combination with OPDIVO (nivolumab) in two distinct treatment settings in a total of 115 previously treated patients with NSCLC:

Median overall survival (mOS) of 24.6 months was observed in previously treated, CPI naïve patients with advanced NSCLC (Cohort A, n=47). This data compares favorably with published data of Checkmate 057, which reported a mOS of 12.2 months in patients who received nivolumab as single agent in a similar treatment setting.
mOS of 11.9 months was reported in NSCLC patients who were previously treated with CPI and whose disease had subsequently progressed (Cohort B, n=68). Published data from other studies stated median OS of 6.8 to 9.0 months for NSCLC patients treated with chemotherapies after CPI progression.
Multiple subset analyses including injection-site reaction (ISR) and tumor PD-L1 expression were performed.
Significantly longer mOS was observed in patients with ISR compared with those without such a reaction for both Cohorts A and B.
Extended survival benefit was observed in PD-L1 positive patients in Cohort A.
A trend of improved overall survival was observed in patients with low blood tumor mutation burden in Cohort B.
Dr. Roger B. Cohen, Professor of Medicine at the University of Pennsylvania Perelman School of Medicine, commented, "HS-110 is a promising agent for treatment of incurable NSCLC. The latest data presented support further clinical evaluation in combination with first line regimens that include a CPI as well as addressing high unmet medical needs for CPI progressors."

Jeff Wolf, Chief Executive Officer of Heat, commented, "This data further reinforces the potential utility of HS-110 in combination with a CPI for multiple treatment settings of NSCLC. The growing body of clinical data demonstrates that HS-110 in combination with a CPI is well tolerated and has the potential to enhance survival benefit when given with a CPI. Our latest results, consistent with previously reported data, provide a strong foundation for the Company to discuss possible Phase 3 registration trial designs with the FDA and potential partners."

About HS-110
HS-110 is a first-in-class, off-the-shelf, allogeneic cell therapy designed to utilize gp96 for immune activation against multiple tumor testis antigens. Phase 2 trial of HS-110 in combination with Bristol Myers Squibb’s OPDIVO (nivolumab) has completed enrollment in patients with incurable or metastatic NSCLC. OPDIVO is a programmed death-1 immune checkpoint inhibitor. HS-110 has broad potential for providing multiple treatment options to NSCLC patients in combination with a PD-1 inhibitor. Positive interim survival data has been demonstrated in two distinct treatment settings in previously treated NSCLC patients who have not been treated with CPI as well as patients who have progressed during or after previous treatment with a CPI. Combination of HS-110 and PD-(L)1 therapies may confer additional survival benefit.

Glycotope Poster Presentation at the 2021 American Society of Clinical Oncology (ASCO) Virtual Annual Meeting

On June 4, 2021 Glycotope GmbH, a biotechnology company developing antibodies against proteins carrying tumor-specific carbohydrate structures, reported it is presenting two posters at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, which is being held virtually this year due to COVID-19 (Press release, Glycotope, JUN 4, 2021, View Source [SID1234583526]).

Henner Kollenberg, Managing Director of Glycotope GmbH commented: "The data presented at ASCO (Free ASCO Whitepaper) highlight our ability to draw on our long-standing expertise in glyco-biology to generate novel biopharmaceuticals targeting cancer indications. The data showed that a Glycotope-developed anti-TA-MUC1 antibody combined with the anti-EGFR Tomuzotuximab or Panitumumab in patients with refractory solid tumors is safe and feasible and exhibited interesting anti-tumour activity."

Poster details are as follows:

Poster 2524

Title: Safety and tolerability results of the GATTO study, a phase Ib study combining the anti-TA-MUC1 antibody Gatipotuzumab with the anti-EGFR Tomuzotuximab or Panitumumab in patients with refractory solid tumors
Session: Poster Session: Developmental Therapeutics—Immunotherapy
Abstract ID: 332635

Download: View Source

Poster 2522
Title: Activity results of the GATTO study, a phase Ib study combining the anti-TA-MUC1 antibody Gatipotuzumab with the anti-EGFR Tomuzotuximab or Panitumumab in patients with refractory solid tumors

Session: Poster Session: Developmental Therapeutics—Immunotherapy
Abstract ID: 329709