On January 18, 2022 I-Mab reported that the first patient has been dosed in its China Phase II trial of lemzoparlimab in combination with the PD-1 antibody toripalimab (TUOYI) in patients with advanced solid tumors (Press release, I-Mab Biopharma, JAN 18, 2022, View Source [SID1234605605]). The phase 2 study is designed as a basket trial and could potentially lead to a registrational trial in China.

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"We are pleased to initiate the phase 2 trial for the combination of lemzoparlimab and toripalimab in patients with advanced solid tumors in China, and looking forward to accelerating its clinical development," said Dr. Andrew Zhu, President at I-Mab. "We are leveraging our translational medicine findings to select tumors with a higher probability of success for this trial."

Lemzoparlimab is a novel CD47 antibody that exerts strong anti-tumor activity while exhibiting minimal binding to red blood cells based on pre-clinical data. It is being evaluated in combination with pembrolizumab (Keytruda) in advanced solid tumors in the U.S. and in patients with NHL and AML/MDS in other ongoing clinical studies in the U.S. and China. In all clinical trials conducted so far, lemzoparlimab has been administered without a priming dose.

About CD47 and Lemzoparlimab

CD47 is a cell surface protein over-expressed in a wide variety of cancers and can act to protect tumors by delivering a "don’t eat me" signal to otherwise tumor-engulfing macrophages. CD47 antibody blocks this signal and enables macrophages to attack tumor cells. However, development of CD47 antibody as a cancer therapy has been hampered by its hematologic side effects, such as severe anemia, caused by natural binding of CD47 antibody to red blood cells. Scientists at I-Mab discovered a novel CD47 antibody, lemzoparlimab, that is designed to target tumor cells while exerting a minimal untoward effect on red blood cells.

Multiple clinical studies are ongoing in both the U.S. and China to explore indications in treating both hematologic malignancies and solid tumors. Lemzoparlimab is being studied in patients with myelodysplastic syndrome (MDS), acute myelocytic leukemia (AML), and advanced solid tumors in combination with chemotherapy and immune checkpoint inhibitors in the U.S. and China. Combined clinical results from these studies could potentially support future registrational trials in China.

In September 2020, I-Mab and AbbVie entered into a global strategic collaboration to develop and commercialize lemzoparlimab. This includes the design and conduct of further clinical trials to evaluate lemzoparlimab in multiple cancers in China and globally. AbbVie has assumed sponsorship of the U.S. study as of April 2021.

On January 18, 2022 Turning Point Therapeutics, Inc. (NASDAQ: TPTX), a precision oncology company developing next-generation therapies that target genetic drivers of cancer, reported updates and anticipated milestones across its 2022 strategic objectives (Press release, Turning Point Therapeutics, 18 18, 2022, View Source [SID1234605604]).

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"As we look to 2022, we are focused on continuing progress across our clinical stage pipeline and expanding our discovery engine," said Athena Countouriotis, M.D., president and CEO. "We are encouraged that all six cohorts in our registration enabling TRIDENT-1 study for our lead drug candidate repotrectinib continue to enroll at a strong pace and we look forward to providing topline BICR data from the ROS1-positive NSCLC cohorts in the second quarter of this year. With our strong balance sheet and organizational growth and leadership, we are well positioned to continue to make rapid progress across our entire portfolio."

The company’s key strategic priorities are:

1. ADVANCE REPOTRECTINIB PROGRAM

The company announced today that the Phase 2 registration enabling TRIDENT-1 study had strong progress across all cohorts for enrollment during the fourth quarter of 2021 with expansion cohort 4 (EXP-4 — ROS1-positive advanced NSCLC population pretreated with one prior TKI without chemotherapy) now fully enrolled with the targeted 60 patients. Enrollment across all six cohorts of the study remains open and continues to progress steadily. Enrollment in EXP-4 is ongoing to provide continued access to new patients.

Data from ROS1-positive TKI-naïve NSCLC patients in the Phase 1 portion of the TRIDENT-1 trial continue to demonstrate best-in-class potential. The duration of response (DOR) for 6 responder patients, among a total of 7 patients treated at or above the recommended Phase 2 dose, ranged from 5.6 to 42.2+ months with 3 patients who had DOR of greater than 30 months. DOR was calculated using blinded independent central review (BICR) assessments as of the data cut-off date of July 22, 2019 followed by physician assessments as of the data cut-off date of November 29, 2021. Duration of treatment for the 7 patients ranged from 10.9 to 45.8+ months with 4 out of 7 patients remaining on treatment for greater than 3 years as of the data cut-off date of November 29, 2021.

The company anticipates discussing with the U.S. Food and Drug Administration (FDA) topline BICR data from all of the ROS1-positive NSCLC cohorts from TRIDENT-1 at a pre-NDA meeting in the second quarter of 2022.The company plans on reporting the BICR results, including both objective response rate (ORR) and DOR, in the second quarter of 2022 prior to the pre-NDA meeting.

The company anticipates providing a clinical data update from the NTRK-positive advanced solid tumor cohorts from TRIDENT-1 in the second half of 2022.

2. ADVANCE OTHER PIPELINE PROGRAMS

ELZOVANTINIB (TPX-0022), MET/SRC/CSF1R INHIBITOR

Patient enrollment continues in the SHIELD-1 study at 40 mg QD to 40 mg BID in Phase 1 dose expansion and in parallel elzovantinib also is being studied at an intermediate dose level (60 mg QD to 60 mg BID) in Phase 1 dose escalation.
The company anticipates providing a clinical data update from the Phase 1 SHIELD-1 study in the second half of 2022.
The company anticipates initiating the Phase 2 portion of the SHIELD-1 study in the second half of 2022, pending FDA feedback on data from the intermediate dose level.

The company anticipates initiating the SHIELD-2 combination study of elzovantinib and aumolertinib in mid-2022, pending clearance of an investigational new drug (IND) application by the FDA.

Aumolertinib is EQRx, Inc.’s drug candidate targeting EGFR, and the combination of aumolertinib and elzovantinib will be studied in this Phase 1b/2 trial in patients with EGFR mutant MET-amplified advanced NSCLC who have progressed following treatment with osimertinib. The study will evaluate the safety, tolerability and preliminary efficacy of the combination regimen.
TPX-0046, RET INHIBITOR

The company continues to progress the dose-finding portion of the Phase 1/2 SWORD-1 study, where the company is evaluating multiple doses and schedules to further characterize the pharmacokinetics, safety, and efficacy profile before determining the RP2D.
TPX-0131, ALK INHIBITOR

The dose finding portion of the Phase 1/2 FORGE-1 study is ongoing. The company anticipates providing early interim data from initial patients treated in the dose-finding portion of the FORGE-1 study in the fourth quarter of 2022 or early 2023.
3. ADVANCE RESEARCH PROGRAMS

The company remains on track to nominate two development candidates in the second half of 2022. The company currently has four internal discovery programs targeting aberrant GTPase signaling known to drive genomically defined cancers with significant unmet medical need. The most advanced programs target KRAS G12D and the p21 activated kinase, or "PAK" family.

The company also plans on providing details on the other 2 GTPase signaling discovery programs during the second half of 2022.
FINANCIAL UPDATE

Based on its current operating plans, the company expects that its cash, cash equivalents and marketable securities of $975-985 million as of December 31, 2021 (unaudited), are sufficient to fund current operations into the second half of 2024.

On January 18, 2022 TC BioPharm reported that Executive Chairman and Founder, Dr. Michael Leek will be participating in Advanced Therapies Week in Miami, Florida January 25-28 (Press release, TC Biopharm, JAN 18, 2022, View Source [SID1234605603]).

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Michael will participate in a session titled, Treating Cancer and Covid – Use of Banked Allogeneic Gamma-Delta T Cells in Oncology and Severe Viral Infection. The presentation will take place on Friday January 28th at 9:50 am ET at the Miami Beach Convention Centre. For more information or to register for the event, please visit; View Source

Dr. Michael Leek has 30 years’ experience in regenerative medicine, during which he progressed 10 different cell-based products from the laboratory into clinic. In 2017, Michael received the ‘Scottish Life-Sciences Entrepreneurial Business Leadership’ award for 2016-2017. Michael is also a Fellow of the Royal Society of Medicine and Honorary Lecturer at the University of Aberdeen, School of Medical Sciences.

Advanced Therapies Week is a large and immersive expo for companies in the cell and gene therapy sector. It has a focus on knowledge sharing, relationship building and deal making to advance a major pillar of medicine.

On January 18, 2022 – Transgene (Euronext Paris: TNG), a biotech company that designs and develops virus-based immunotherapeutics against cancer, and PersonGen BioTherapeutics, a Chinese biotech company at clinical trial stage, which is developing breakthrough and innovative CAR-T cell therapies for solid tumors and hematologic tumors, reported a strategic collaboration to evaluate the feasibility and efficacy of combination therapy associating PersonGen’s TAA06 CAR-T cell injection with intravenous (IV) administration of an armed oncolytic virus, from Transgene’s Invir (Press release, Transgene, 18 18, 2022, View Source [SID1234605602]). IO platform, in solid tumors including pancreatic cancer and brain glioma. The collaboration aims to demonstrate the combination’s likely synergistic mechanisms to potentiate CAR-T cell therapy.

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Under the terms of the collaboration agreement, Transgene will develop multiple new OV
candidates, using its patented oncolytic virus backbone VVcopTK-RR- and its Invir.IO technology
platform, specifically for IV administration in combination with PersonGen’s TAA06 CAR-T
injection. PersonGen will evaluate the efficacy of the combination to eliminate solid tumors in
preclinical models.

While CAR-T cell drugs have achieved great success in the treatment of hematological tumor
therapies, there are many clinical challenges with the use of these novel therapies to treat solid
tumors. One of the most critical obstacles is that the solid tumor microenvironment not only
obstructs the homing of CAR-T cells, but also inhibits CAR-T cells’ function. In addition, the high
heterogeneity of solid tumors also facilitates immune escape from CAR-T cell therapy.
TAA06, has been independently developed by PersonGen, which has filed an investigational new
drug (IND) application for this novel CAR-T therapy in China and will initiate the IND in the US later
this year. Preclinical studies with TAA06, including pharmacodynamic data have shown superior
in vivo and in vitro therapeutic efficacy in solid tumors.

Patented VVcopTK-RR- oncolytic viruses developed with Transgene’s Invir.IO platform are able to:
• selectively replicate in cancer cells leading to tumor lysis; effectively release antitumor payloads into the tumor;
• stimulate an immune response locally in the tumor, thus optimizing the safety profile
of the virus with the added potential to transform a "cold" tumor into a "hot" tumor.
Clinical and preclinical data has demonstrated that after IV administration, VVcopTK-RR- oncolytic
viruses selectively replicate and persist in tumor cells leading to the local expression of its
functional payload*
.
Based on these highly supportive data, Transgene and PersonGen believe that combining
Transgene’s OV and PersonGen’s CAR-T therapies could overcome the challenges of solid tumor
heterogeneity by improving the tumor microenvironment.

On January 18, 2022 Cardiff Oncology reported new data from its lead clinical program evaluating onvansertib in combination with standard-of-care (SOC) FOLFIRI/bevacizumab for second-line treatment of patients with KRAS-mutated metastatic colorectal cancer (mCRC) (Press release, Cardiff Oncology, JAN 18, 2022, View Source [SID1234605601]). A subset of these data will be featured in a poster presented by Dr. Heinz-Josef Lenz, principal investigator, USC Norris Comprehensive Cancer Center, at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium (ASCOGI) on Saturday, January 22, 2022.

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"As we have increased the number of patients evaluated and the duration of follow-up, our Phase 1b/2 trial has consistently generated data suggesting that onvansertib provides meaningful clinical benefits when added to SOC," said Katherine L. Ruffner, M.D., chief medical officer of Cardiff Oncology. "The objective response rate and median progression free survival observed substantially exceed what would be expected with SOC alone, and five patients receiving onvansertib have been able to pursue potentially curative metastasis-directed treatments. We also observed a confirmed complete response, which is exciting given the difficult-to-treat nature of second line mCRC patients."

The most current data for the trial are shown below and include patient follow up collected after the cutoff dates for both the ASCO (Free ASCO Whitepaper)-GI abstract and poster (one additional PR was recorded after December 3):

Efficacy data in evaluable patients (represents an update from ASCO (Free ASCO Whitepaper)-GI abstract/poster):

Among patients treated per protocol at the recommended Phase 2 dose (RP2D; 15 mg/m2) in combination with FOLFIRI-bev:
12 of 35 (34%) achieved an initial complete response (CR) or partial response (PR)
10 of 35 (29%) achieved a confirmed CR or PR (awaiting confirmatory scan for 1 patient)
33 of 35 (94%) had a best response of disease control (CR + PR + SD)
Objective response rates of 5-13% observed in historical control trials in similar patient populations treated with various different drug combinations, including the standard of care chemotherapy of FOLFIRI with bevacizumab1-4
Patients evaluable for response treated at all dose levels (12 mg/m2, 15 mg/m2, 18 mg/m2)
17 of 48 (35%) achieved an initial CR or PR
13 of 48 (27%) have achieved a confirmed CR or PR (awaiting confirmatory scan for 1 patient)
44 of 48 (92%) had a best response of disease control (CR + PR + SD)
Status of 4 unconfirmed PRs:
1 patient discontinued from the trial prior to confirmatory scan due to an adverse event that was unrelated to treatment (hepatitis B)
1 patient went from PR to SD at the confirmatory scan and patient subsequently discontinued from the trial to pursue potentially curative metastasis-directed therapy
1 patient went from PR to SD at the confirmatory scan (patient remains on treatment)
1 patient has yet to have their confirmatory scan
5 of 48 (10%) evaluable patients discontinued therapy to pursue potentially curative metastasis-directed therapy (surgery or microwave ablation), including 2 patients with SD
Median progression free survival (mPFS; no update from ASCO (Free ASCO Whitepaper)-GI poster)

mPFS has not yet been reached in patients treated per protocol at the RP2D
mPFS across all response-evaluable patients (n = 48) is 9.4 months (95% confidence interval: 7.1 – not yet reached)
mPFS of ~4.5-5.7 months has been reported in trials used as historical controls1-4
Biomarker data across all patients (no update from ASCO (Free ASCO Whitepaper)-GI poster):

Responses (CRs or PRs) were observed across seven different KRAS mutation variants, including the 3 most commonly observed in colorectal cancer (G12D, G12V, G13D)
Patients achieving a best response of a CR or PR showed the greatest decreases in plasma KRAS mutant allelic frequency (MAF) measured by droplet digital PCR (ddPCR) after 1 cycle (28 days) of therapy
Safety data across all patients (no update from ASCO (Free ASCO Whitepaper)-GI poster):

The combination of onvansertib and FOLFIRI/bevacizumab was shown to be well-tolerated with only 11% (84/788) of reported treatment-emergent adverse events (TEAEs) being G3/G4
The most commonly reported adverse event was neutropenia/neutrophil count decreased
Most reported TEAEs were manageable and reversible with supportive care
Baseline characteristics of patients at all dose levels (no update from ASCO (Free ASCO Whitepaper)-GI poster):

The patients’ median age was 61 years (range 35-83), and 56% were male
67% patients had previously received bevacizumab
16 of 48 (33%) evaluable patients remain on trial at the data cutoff date
Mark Erlander, Ph.D., chief executive officer of Cardiff Oncology, commented, "These impressive results show radiographic responses across multiple KRAS mutation variants when onvansertib is combined with the standard of care regimen of FOLFIRI-bev and demonstrate a substantial increase in disease response relative to historical controls. We believe the data presented today further validate the potential of onvansertib to provide a meaningful improvement in the treatment outcome of a large patient population that has limited available treatment options. Looking forward, and with our strong cash position, we have the ability to explore the full potential of onvansertib."

Webcast and Conference Call

The newly announced data are being discussed today at 5:00 PM ET as part of a webcast and conference call with members of the Cardiff Oncology management team. To access the webcast, click here. To participate by phone, please dial 1-877-407-9208 (domestic) or 1-201-493-6784 (international) and refer to conference ID 13725845. Following the live event, an archived webcast will be available on the "Events" section of the Cardiff Oncology website.

About the Phase 1b/2 Trial of Onvansertib in the Second-Line Treatment of KRAS-mutated mCRC

This is a multi-center, single-arm, Phase 1b/2 trial of onvansertib in combination with standard-of-care FOLFIRI and Avastin (bevacizumab) to evaluate the safety and preliminary efficacy of the combination regimen in the second-line treatment of patients with KRAS-mutated mCRC. The trial, A Phase 1b/2 Study of Onvansertib (PCM-075) in Combination with FOLFIRI and Bevacizumab for Second–Line Treatment of Metastatic Colorectal Cancer in Patients with a KRAS Mutation, is enrolling patients with histologically confirmed metastatic and unresectable colorectal carcinoma harboring a KRAS mutation. Patients must also have experienced disease progression or treatment intolerance to first-line treatment with fluoropyrimidine and oxaliplatin (FOLFOX or CapeOx) with or without bevacizumab to be eligible. The trial is being conducted at the following cancer centers across the U.S.: USC Norris Comprehensive Cancer Center, The Mayo Clinic (Arizona, Rochester, and Jacksonville), Kansas University Medical Center (KUMC), CARTI Cancer Center and Inova Schar Cancer Institute. For more information on the trial, please visit NCT03829410.

References

Giessen et al., Acta Oncologica 2015, 54: 187-193
Cremolini et al., Lancet Oncol 2020, 21: 497–507
Antoniotti et al., Correspondence Lancet Oncol June 2020
Bennouna et al., Lancet Oncol 2013; 14: 29–37