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Immunocore announces initial Phase 1 data of ImmTAC® candidate IMC-C103C targeting MAGE-A4

On 6 December 2021 Immunocore Holdings Plc (Nasdaq: IMCR), a late-stage biotechnology company pioneering the development of a novel class of T cell receptor (TCR) bispecific immunotherapies designed to treat a broad range of diseases, including cancer, infectious and autoimmune disease, reported the initial Phase 1 data of IMC-C103C, a bispecific T cell engager targeting MAGE-A4, in selected advanced solid tumors (Press release, Immunocore, DEC 6, 2021, View Source [SID1234596499]).

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IMC-C103C was developed using the company’s innovative ImmTAC technology platform and is being developed in partnership with Genentech, a member of the Roche Group. The trial (IMC-C103C-101) includes a Phase 1 dose escalation to evaluate safety, maximum tolerated dose / expansion dose, and preliminary clinical activity. The initial Phase 1 data from this study is the subject of a presentation at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Immuno-Oncology Congress.

The presentation includes data from 44 patients enrolled across 10 dose-escalation cohorts. Indications with high MAGE-A4 prevalence (eg. serous ovarian, synovial sarcoma) enrolled all-comers with retrospective MAGE-A4 testing by immunohistochemistry (IHC) while other indications required prospective confirmation of tumor MAGE-A4 expression by IHC.

IMC-C103C demonstrated a manageable safety profile. The most common any-grade, treatment-related adverse events were consistent with cytokine release syndrome, were dose dependent and rapidly resolved. The most common related grade 3 or grade 4 adverse event was neutropenia, typically at doses ≥ 90 micrograms. Neutropenia was reversible, with treatment interruption or G-CSF, and was not dose-limiting. None of the treatment-related AEs led to discontinuation or death.

IMC-C103C dose escalation began at 0.5 micrograms, the minimum anticipated biological effect level (MABEL), and includes 10 cohorts to date. Pharmacodynamic biomarkers of T cell activation were first observed at 15 micrograms and became consistent and robust at doses ≥ 90 micrograms. IMC-C103C treatment results in a substantial increase in T cell infiltration in tumor biopsies relative to baseline.

The most frequently enrolled patients had platinum relapsed/refractory ovarian cancer, who were enrolled regardless of their tumor MAGE-A4 protein expression. Most of these patients had low or no MAGE-A4 protein expression in their tumors as measured by IHC (median H score = 8). One ovarian cancer patient, with a very low MAGE protein expression, treated at a dose of < 90 micrograms, had a durable confirmed partial response (PR) with 8.3 months duration. An additional ovarian cancer patient at a dose of ≥ 90 micrograms, also with very low MAGE-A4 protein expression, has a confirmed partial response ongoing at 4.4+ months. One of the three non-ovarian cancer patients (head and neck squamous cell carcinoma) at a dose of ≥ 90 micrograms has a confirmed PR that is ongoing.

"IMC-C103C is our second T cell engager to demonstrate durable clinical activity, now in multiple solid tumors," stated Bahija Jallal, Chief Executive Officer. "We are highly encouraged to see these responses in ovarian and head and neck cancer. The durable PRs in ovarian cancer occur in heavily pre-treated patients even with low MAGE-A4 protein tumor expression. We have initiated an expansion arm in ovarian carcinoma, while we continue signal searching and determining the optimal dose in multiple solid tumors."

Earlier this month, Immunocore initiated an expansion arm in high grade serous ovarian carcinoma at 140 micrograms. IMC-C103C-101 will continue to explore the optimal dose and evaluate clinical activity in multiple solid tumors. The company plans to present additional data from this program in 2022. IMC-C103C is part of a co-development / co-promotion collaboration with Genentech under which Immunocore shares program costs and profits equally.

Conference Call Information
Immunocore will host a live webcast and conference call today beginning at 8:00 am E.T. to discuss the results with Dr. Diwakar Davar, an assistant professor of medicine and a medical oncologist and hematologist at the University of Pittsburgh Medical Center (UPMC). A live webcast of the conference call will be available under "Events" in the Investor Relations section of Immunocore Holdings’ website at www.immunocore.com. The presentation from today’s call and the archived webcast will be available on Immunocore’s website after the conference call concludes and will be available for 30 days following the call.

Spectrum Pharmaceuticals Submits New Drug Application for Poziotinib

On December 6, 2021 Spectrum Pharmaceuticals (NasdaqGS: SPPI), a biopharmaceutical company focused on novel and targeted oncology therapies, reported that it has submitted its New Drug Application (NDA) for poziotinib to the U.S. Food and Drug Administration (FDA) for use in patients with previously treated locally advanced or metastatic non-small cell lung cancer (NSCLC) with HER2 exon 20 insertion mutations (Press release, Spectrum Pharmaceuticals, DEC 6, 2021, View Source [SID1234596498]). The NDA submission is based on the positive results of Cohort 2 from the ZENITH20 clinical trial, which assessed the safety and efficacy of poziotinib. The product has received Fast Track designation and there is currently no treatment specifically approved by the FDA for this indication.

"The NDA submission for poziotinib marks an important step in achieving a first treatment for patients with HER2 exon 20 insertion mutations in lung cancer," said Joe Turgeon, President and CEO of Spectrum Pharmaceuticals. "I want to thank the patients, investigators and our internal staff who have passionately worked to achieve this important milestone in an area of high unmet medical need."

ZENITH20 Cohort 2 Clinical Results Summary

Results for Cohort 2 of the ZENITH20 clinical trial have been published in the Journal of Clinical Oncology (November 29, 2021), and can be accessed by clicking here.

Cohort 2 enrolled 90 patients who received an oral once daily dose of 16 mg of poziotinib. The intent-to-treat analysis demonstrated a confirmed objective response rate (ORR) of 27.8% (95% Confidence Interval (CI), 18.9%-38.2%). The observed lower bound of 18.9% exceeded the pre-specified lower bound of 17%. The median duration of response was 5.1 months and the median progression free survival was 5.5 months. In this cohort, 87% of patients had drug interruptions with 11 patients (12%) permanently discontinuing due to adverse events. 13 patients (14%) had treatment-related serious adverse events. As previously announced, the company had a successful pre-NDA meeting with the FDA which resulted in an agreement to submit an NDA for poziotinib. During the meeting, Spectrum confirmed with the FDA that Cohort 2 data could serve as the basis of an NDA submission. The company will continue to work with the FDA as appropriate, while the agency conducts its review.

About the ZENITH20 Clinical Trial

The ZENITH20 study consists of seven cohorts of NSCLC patients. Cohorts 1 (EGFR) and 2 (HER2) in previously treated NSCLC patients with exon 20 mutations and Cohort 3 (EGFR) in first-line patients have completed enrollment. Cohort 4 (HER2) in first-line NSCLC patients with exon 20 mutations is still enrolling patients. Cohorts 1- 4 are each independently powered for a pre-specified statistical hypothesis and the primary endpoint is objective response rate (ORR). Cohort 5 includes previously treated or treatment-naïve NSCLC patients with EGFR or HER2 exon 20 insertion mutations. Cohort 6 includes NSCLC patients with classical EGFR mutations who progressed while on treatment with first-line osimertinib and developed an additional EGFR mutation. Cohort 7 includes NSCLC patients with a variety of less common mutations in EGFR or HER2 exons 18-21 or the extracellular or transmembrane domains.

Autolus Therapeutics announce new time for investor call to discuss data presented at the 63rd ASH Annual Meeting & Exposition

On December 6, 2021 Autolus Therapeutics plc (Nasdaq: AUTL), a clinical-stage biopharmaceutical company developing next-generation programmed T cell therapies, reported it will hold a conference call to discuss the data being presented at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition, being held between December 11-14, 2021 (Press release, Autolus, DEC 6, 2021, View Source [SID1234596497]). Note this is a change to the timing announced previously.

New timing of investor call

Management will host a conference call and webcast on Monday, December 13, 2021, at 8:00 am ET/1:00 pm GMT to discuss the ASH (Free ASH Whitepaper) data. To listen to the webcast and view the accompanying slide presentation, please go to the events section of Autolus’ website.

Merus Presents Clinical Data on MCLA-145 at the ESMO Immuno-Oncology Congress 2021

On December 6, 2021 Merus N.V. (Nasdaq: MRUS) ("Merus", "the Company", "we", or "our"), a clinical-stage oncology company developing innovative, full-length multispecific antibodies (Biclonics and Triclonics), reported that clinical data on MCLA-145 from the phase 1 trial in patients with solid tumors at the ESMO (Free ESMO Whitepaper) Immuno-Oncology Congress 2021 being held virtually (Press release, Merus, DEC 6, 2021, View Source [SID1234596496]).

"We are encouraged by the progress we are making with MCLA-145," said Dr. Andrew Joe, Chief Medical Officer. "Patients have been treated at 8 dose levels with preliminary evidence of antitumor activity observed, as we continue to explore MCLA-145 as monotherapy."

MCLA-145

The reported data are from the phase 1 open-label, multicenter dose escalation study, of bispecific antibody MCLA-145 in patients with solid tumors. The primary objective is to evaluate the safety, tolerability, and dose-limiting toxicity (DLT) of MCLA-145 and to determine maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE).

Observations in the presentation include:

As of the data cutoff date of July 14, 2021, 34 patients with advanced or metastatic solid tumors with median age of 60.5 (range 27-81) years have been treated at 8 dose levels ranging from 0.4-75mg Q2W
Median (range) duration of treatment with MCLA 145 was approximately 6 (1–74) weeks
Reported adverse events (AEs) have been managed with drug interruption and/or administration of steroids in some patients
Treatment-emergent AEs (TEAEs) occurred in 33 patients (97.1%); treatment-related TEAEs occurred in 23 patients (67.6%), most commonly fatigue (n=6, 17.6%) and decreased neutrophil count (n=6, 17.6%)
DLTs defined as within 28 days from the first infusion occurred in 4 patients (11.8%)
Laboratory alanine transaminase/aspartate transaminase (ALT/AST) elevations of any grade were observed in 15 patients (44.1%), with grade ≥3 ALT/AST elevations in 6 patients (17.6%)
Preliminary evidence of antitumor activity has been observed at doses ≥25 mg biweekly
Peripheral blood shows robust T-cell activation, including activation of cytotoxic CD8+ cells and cytokines, across the 10 to 75 mg biweekly dosing range
Further evaluation of optimal dose and efficacy in PD-L1+ tumors is planned.
The phase 1 clinical trial of MCLA-145 consists of a dose escalation phase, followed by a planned dose expansion phase. MCLA-145 is the first drug candidate co-developed under Merus’ global collaboration and license agreement with Incyte, which permits the development and commercialization of up to 11 bispecific and monospecific antibodies from the Merus Biclonics platform. Merus retains full rights to develop and commercialize MCLA-145, if approved, in the United States; and Incyte holds full rights to develop and commercialize MCLA-145 outside the United States.

Adicet Bio Announces Positive Interim Clinical Data From First-Ever Allogeneic, Off-The-Shelf, Gamma Delta CAR T Investigational Cell Therapy

On December 6, 2021 Adicet Bio, Inc. (Nasdaq: ACET), a biotechnology company discovering and developing first-in-class allogeneic gamma delta CAR T cell therapies for cancer and other diseases, reported positive interim data from its dose escalation Phase 1 study evaluating the safety and tolerability of ADI-001, Adicet’s investigational therapy targeting CD20 for the potential treatment of B-cell Non-Hodgkin’s Lymphoma (Press release, Adicet Bio, DEC 6, 2021, View Source [SID1234596495]).

As of the November 22, 2021 data cutoff, six patients had been enrolled and received ADI-001. The first two patients enrolled in the lowest dose level tested did not reach the day 28 assessment and were not evaluable for efficacy per protocol. Three of the four evaluable patients achieved responses, including two complete responses (CR) and one partial response (PR) that investigators characterized as near complete response. Patients were heavily pre-treated, with a median of five lines of prior systemic therapy, including a patient who had received prior autologous CD19 CAR T, and achieved complete response following a single infusion of ADI-001 administered at the lowest dose level.

"We are extremely excited to see such profound early complete responses in our Phase 1 dose-finding study evaluating ADI-001 as monotherapy among patients with very advanced cancer starting at our first dose level of 30 million CAR+ cells," said Chen Schor, President and Chief Executive Officer of Adicet Bio. "Data to-date suggest that ADI-001 is highly clinically active. We look forward to reporting additional data in the first half of 2022 and to rapidly progressing our pipeline to realize the full potential of our gamma delta CAR T cell platform for patients."

"The unequivocal responses to ADI-001 in this heavily pre-treated patient population at such low dose levels are highly promising," said Sattva Neelapu M.D., Professor in the Department of Lymphoma/Myeloma at The University of Texas MD Anderson Cancer Center. "These data suggest that ADI-001 has the potential to be an effective treatment option for B cell malignancies if confirmed in further clinical testing. ADI-001 does not require gene editing and provides complementary innate, adaptive, and CAR mediated antitumor effects which may improve durability and minimize emergence of tumor resistance."

Of the four efficacy evaluable patients, three received ADI-001 at dose level one (30 million CAR+ cells) and one received ADI-001 at dose level two (100 million CAR+ cells). In dose level one, one patient achieved a CR, one patient achieved a PR that was characterized as near CR and one patient had progressive disease (PD). In dose level two, the first patient achieved a CR.

All evaluable patients had been heavily pre-treated with a median of five lines of prior systemic therapies. Of the three patients who achieved PR or better under Lugano 2014 criteria (ORR=75%, CR=50%), one had diffuse large B-cell lymphoma (DLBCL) with five prior lines of therapy including two cycles of anti-CD19 CAR T cell therapy, one had follicular lymphoma transformed into a large B-cell tumor with four prior lines of therapy, and the third had mantle cell lymphoma with five prior lines of therapy. These patients achieved two CRs and a near CR.

Overall, ADI-001 infusions were generally well-tolerated. No dose-limiting toxicities, graft vs host disease (GvHD), Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) or grade 3 or higher Cytokine Release Syndrome (CRS) have been reported to-date, suggesting a potentially wide therapeutic window for ADI-001.

A significant increase in circulating IL-15 was observed during the 28-day window following lymphodepletion, potentially providing cytokine support for the proliferation of ADI-001. Emergence of circulating ADI-001 in the blood was observed by quantitative polymerase chain reaction and by flow cytometry, demonstrating expansion of ADI-001 in patients. Elevations in additional circulating cytokines, primarily IL-2 and IL-8 were observed during the first 14 days from dosing, consistent with the activation profile of ADI-001 and similar to the observed time-to-peak for cytokines previously reported in association with autologous alpha-beta CAR T cells. Importantly, no meaningful increases in IL-6 were seen in association with ADI-001, except for one patient who experienced COVID-19 infection, suggesting reduced likelihood for ICANS and high-grade CRS.

"It is remarkable to see our early preclinical studies translate to the clinic. The preliminary safety and efficacy data from low-dose ADI-001 collected to date indicate the potential for a broad therapeutic window. Without the need for gene editing and its associated safety concerns, our platform is designed to preserve the natural innate and adaptive anti-tumor activity of gamma delta CAR T cells, which we believe may lead to better durability," said Francesco Galimi, M.D., Ph.D., Senior Vice President and Chief Medical Officer of Adicet Bio. "As we look to expand into additional cohorts, we plan to leverage our scalable off-the-shelf manufacturing process to meet future needs. We look forward to advancing our novel allogeneic gamma delta T cell pipeline for cancer patients."

Table 1: Summary of ADI-001 interim data from two dosing cohorts*:

Dose Level Age/Sex B-cell lymphoma subtypes # Prior lines of therapies Prior CAR T? Best Response (BOR) by Lugano Criteria (2014)
30 million CAR+ cells

62/F Transformed DLBCL
(from chronic lymphocytic leukemia) 5 prior lines No PD
66/F Transformed high grade
B cell tumor (from follicular lymphoma) 4 prior lines

No PR
(Near CR)
75M DLBCL 5 prior lines Yes (liso-cel) CR
100 million CAR+ cells 62/M Mantle cell lymphoma 5 prior lines No CR
*Efficacy evaluable patients as of November 22, 2021 database entry. Data are subject to further review and verification.

Webcast/Conference Call Information
Adicet will host a live presentation on Monday, December 6 at 8:30am EST to discuss the results. Dr. Sattva Neelapu from the University of Texas MD Anderson Cancer Center will participate in the event.

The live webcast of the presentation can be accessed under "Presentations & Events" in the investors section of the Company’s website at www.adicetbio.com or by dialing (877) 800-3802 (domestic) or (615) 622-8057 (international) and reference the conference ID 6952318. The archived webcast will be available on the Company’s website beginning approximately two hours after the event.

About ADI-001
ADI-001 is an investigational allogeneic gamma delta CAR T cell therapy being developed as a treatment for B-cell non-Hodgkin’s lymphoma. ADI-001 targets malignant B-cells via an anti-CD20 CAR and via the gamma delta innate and T cell endogenous cytotoxicity receptors. Gamma delta T cells engineered with an anti-CD20 CAR have demonstrated potent antitumor activity in preclinical models, leading to long-term control of tumor growth.

About the GLEAN Study
This Phase I study is an open-label, multi-center study of ADI-001 enrolling adults diagnosed with B cell malignancies who have either relapsed, or are refractory to at least two prior regimens. The primary objectives of the study are to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of ADI-001, and to determine optimal dosing as a monotherapy. The study is expected to enroll approximately 75 patients. For more information about the clinical study design, please visit: www.clinicaltrials.gov (NCT04735471).