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Harbour BioMed Announces Positive Phase II Results for HBM4003 and Tislelizumab Combination in MSS mCRC

On October 22, 2025 Harbour BioMed (HKEX: 02142), a global biopharmaceutical company focused on the discovery and development of novel antibody therapeutics in immunology and oncology, reported positive Phase II clinical data for porustobart (HBM4003), a next-generation, fully human heavy-chain-only anti-CTLA-4 antibody, in combination with tislelizumab, in patients with microsatellite stable (MSS) metastatic colorectal cancer (mCRC).

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The multicenter, open-label Phase II study (NCT05167071) enrolled 24 heavily pretreated patients with non-liver-metastatic (NLM) MSS mCRC. Patients received HBM4003 (0.3 mg/kg) plus tislelizumab (200 mg) every 21 days. The primary efficacy endpoint was objective response rate (ORR) per RECIST 1.1 criteria. The findings showed promising antitumor activity and a manageable safety profile for the combination therapy in this difficult-to-treat population.

Key findings include:

Baseline: All patients (N=24) had received ≥2 prior lines of therapy; 16/24 (66.7%) had lung metastases.
Efficacy: Among the 23 evaluable patients, the combination therapy achieved:
Objective Response Rate (ORR): 34.8% (8 partial responses)
Disease Control Rate (DCR): 60.9% (8 partial responses + 6 stable diseases)
Median Progression-Free Survival (mPFS): 4.2 months
Safety: The regimen was well-tolerated, with no Grade 4 or fatal treatment-emergent adverse events (TEAEs) observed.
TRAEs were reported in 87.5% (21/24) of patients, most commonly (incidence ≥20%) liver function test abnormalities, hematological abnormalities, and pyrexia (mostly Grade 1-2).
Treatment-related serious adverse events (SAEs) occurred in 37.5% (9/24) of patients.
Dr. Jingsong Wang, Founder, Chairman and CEO of Harbour BioMed commented: "The 2025 Nobel Prize in Physiology or Medicine was awarded to three immunologists for their groundbreaking discoveries in regulatory T cells (Treg cells) and their role in controlling the immune system. HBM4003, a next-generation anti-CTLA-4 antibody discovered through our HCAb Harbour Mice platform, is a direct clinical application arising from this foundational research. The positive results from this Phase II clinical study mark an important milestone for Harbour BioMed and underscore the therapeutic potential of HBM4003. We will continue to advance HBM4003 with the goal of delivering transformative immuno-oncology therapies to patients worldwide."

About Porustobart (HBM4003)

Porustobart (HBM4003) is a next-generation, fully human heavy-chain-only anti-CTLA-4 antibody discovered and developed using the HCAb Harbour Mice platform. It is also the first fully human heavy-chain-only antibody which entered clinical development globally. Compared with conventional CTLA-4 antibodies, porustobart has unique, favourable properties, including significant Treg cell depletion and optimized pharmacokinetics for improved safety. Additionally, by enhancing antibody-dependent cellular cytotoxicity (ADCC), porustobart increases the potential to selectively deplete intratumoral Treg cells, helping to overcome the efficacy and toxicity bottleneck of current CTLA-4 therapies. The Company has implemented a global development plan for multiple types of solid tumors with an adaptive treatment design for porustobart. Positive efficacy and safety data have been observed in the monotherapy trial targeting advanced solid tumors, as well as in combination trials with PD-1 inhibitors for melanoma, CRC, NEN and HCC. Final data from the study of HBM4003 in combination with toripalimab for advanced HCC were published in Clinical Cancer Research in August 2025.

(Press release, Harbour BioMed, OCT 22, 2025, View Source [SID1234656903])

Revolution Medicines to Present Updated Elironrasib Safety and Efficacy Data in Patients with KRAS G12C Non-Small Cell Lung Cancer Following Treatment with a KRAS(OFF) G12C Inhibitor

On October 22, 2025 Revolution Medicines, Inc. (Nasdaq: RVMD), a late-stage clinical oncology company developing targeted therapies for patients with RAS-addicted cancers, reported updated clinical data for elironrasib, a RAS(ON) G12C-selective inhibitor, in previously treated patients with KRAS G12C non-small cell lung cancer (NSCLC) who had received a prior KRAS(OFF) G12C inhibitor. These results will be highlighted in an oral presentation at the AACR (Free AACR Whitepaper)-NCI-EORTC Symposium on Molecular Targets and Cancer Therapeutics in Boston, October 23-25.

"The compelling clinical activity, durable response and acceptable tolerability profile seen with elironrasib underscore the potential of this differentiated RAS(ON) G12C-selective inhibitor, including in patients who have progressed on G12C(OFF) inhibitors," said Mark A. Goldsmith, M.D., Ph.D., chief executive officer and chairman of Revolution Medicines. "These findings reinforce the promise of our RAS(ON) inhibitor platform to deliver a range of therapies that target the active, GTP-bound state of RAS proteins with the potential to create new global standards of care."

As of the August 4, 2025 data cutoff date, patients with KRAS G12C NSCLC, who had received prior therapy with a KRAS(OFF) G12C inhibitor, were treated with elironrasib at the recommended Phase 2 dose of 200 mg orally twice daily (BID) and were evaluated on key safety and antitumor activity endpoints. These patients (n=24) were heavily pretreated, with a median of three prior lines of therapy (range 2-6), with 92% (22 out of 24 patients) having progressed on a prior KRAS(OFF) G12C inhibitor. Elironrasib demonstrated compelling antitumor activity, with a confirmed objective response rate of 42% (95% CI: 22-63) and a disease control rate of 79% (95% CI: 58-93). The median duration of response was 11.2 months (95% CI: 5.9-not estimable), and the median progression-free survival was 6.2 months (95% CI: 4.0-10.3). The median overall survival (OS) was not yet reached and 12-month OS rate was 62% (95% CI: 40-78).

These results are from RMC-6291-001, an ongoing multicenter, Phase 1 trial designed to evaluate elironrasib (RMC‑6291) monotherapy in patients with advanced KRAS G12C solid tumors.

Elironrasib is an innovative, mutant-selective inhibitor that binds selectively and covalently to the oncogenic RAS(ON) form of the RAS G12C variant that drives approximately 12% of cases of NSCLC. Revolution Medicines is exploring elironrasib monotherapy and combinations in various treatment settings and continues work to prioritize among multiple options for advancing its development. In July 2025, elironrasib was granted Breakthrough Therapy Designation for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic NSCLC who have received prior chemotherapy and immunotherapy but have not been previously treated with a KRAS G12C inhibitor.

NSCLC accounts for 80%-85% of all lung cancers, and most patients have advanced or metastatic disease at initial diagnosis.1,2 KRAS mutations are found in nearly 30% of NSCLC cases, among which KRAS G12C is the most common.

Advancing RAS(ON) Inhibitor Platform Across Tumor Types
Jan Smith, Ph. D., chief scientific officer of Revolution Medicines will also highlight encouraging preclinical data supporting the RAS(ON) inhibitor doublet of zoldonrasib and daraxonrasib during a plenary session at the start of the AACR (Free AACR Whitepaper)-NCI-EORTC Symposium.

Several other presentations to be featured at the meeting demonstrate continued progress across Revolution Medicines’ RAS(ON) inhibitor portfolio, including:

"Targeting the Oncogenic State of RAS with Tri-Complex Inhibitors"
"RAS(ON) Inhibitor In-Pathway Combinations Maximize RAS Pathway Suppression in KRAS Mutant CRC Models"
"Resistance Mechanisms to Monotherapy Daraxonrasib (RMC-6236) in RAS Mutant PDAC"
"RASolve 301: A Phase 3 Study of Daraxonrasib (RMC-6236) vs. Docetaxel in RAS-Mutant NSCLC"
Further details and information on presentations can found on the AACR (Free AACR Whitepaper)-NCI-EORTC Symposium website.

About Non-Small Cell Lung Cancer
More than 197,000 people are diagnosed with non-small cell lung cancer (NSCLC) in the U.S. each year.3 Despite treatment advancements, NSCLC remains a leading cause of cancer-related mortality worldwide, primarily due to its late-stage diagnosis and limited response to conventional therapies.

(Press release, Revolution Medicines, OCT 22, 2025, View Source [SID1234656902])

Nurix Therapeutics Announces $250.0 Million Registered Offering of Common Stock

On October 22, 2025 Nurix Therapeutics, Inc. (Nasdaq: NRIX), a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of targeted protein degradation medicines in oncology and autoimmune disease, reported the pricing of its underwritten registered offering of 24,485,799 shares of its common stock at a price of $10.21 per share. The gross proceeds to Nurix from the offering, before deducting underwriting discounts and commissions and other offering expenses payable by Nurix, are expected to be $250.0 million. The offering is expected to close on or about October 23, 2025, subject to the satisfaction of customary closing conditions. All of the securities are being offered by Nurix.

The offering includes participation from both new and existing investors including General Atlantic, Redmile Group, Braidwell LP, Deep Track Capital, Perceptive Advisors, Trails Edge Capital Partners and Vestal Point Capital, as well as other healthcare-dedicated funds.

J.P. Morgan Securities LLC, Jefferies LLC and Stifel, Nicolaus & Company, Incorporated are acting as joint book-running managers for the offering. Oppenheimer & Co. Inc. and Robert W. Baird & Co. Incorporated are acting as lead managers for the offering.

Nurix currently intends to use any net proceeds from this offering primarily to fund clinical development of its drug candidates, including the clinical development of bexobrutideg (NX-5948) in chronic lymphocytic leukemia (CLL) and for the exploration of potential autoimmune indications, to fund research and development activities to expand its pipeline and for working capital and general corporate purposes.

The offering is being made pursuant to a shelf registration statement on Form S-3 (File No. 333-280117) that was previously filed by Nurix with the Securities and Exchange Commission ("SEC") and declared effective on June 11, 2024. A prospectus supplement and accompanying prospectus relating to and describing the terms of the offering will be filed with the SEC and will be available on the SEC’s website at www.sec.gov. A copy of the prospectus supplement relating to the offering, when available, may be obtained from: J.P. Morgan, c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY 11717, or by email at [email protected] and [email protected]; Jefferies LLC, Attention: Equity Syndicate Prospectus Department, 520 Madison Avenue, New York, New York 10022, by telephone at (877) 821-7388, or via email at [email protected]; or Stifel, Nicolaus & Company, Incorporated, Attention: Prospectus Department, One Montgomery Street, Suite 3700, San Francisco, CA 94104, by telephone at (415) 364-2720, or via email at [email protected].

This press release shall not constitute an offer to sell or the solicitation of an offer to buy any securities of Nurix, 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.

(Press release, Nurix Therapeutics, OCT 22, 2025, View Source [SID1234656901])

Nurix Initiates DAYBreak™ Pivotal Study of Bexobrutideg in Relapsed or Refractory Chronic Lymphocytic Leukemia

On October 22, 2025 Nurix Therapeutics, Inc. (Nasdaq: NRIX), a clinical stage biopharmaceutical company focused on the discovery, development, and commercialization of targeted protein degradation medicines in oncology and autoimmune disease, reported the initiation of the DAYBreak clinical trial, a pivotal single-arm Phase 2 study of bexobrutideg (NX-5948) in patients with relapsed or refractory chronic lymphocytic leukemia.

DAYBreak and the planned Phase 3 confirmatory study of bexobrutideg will evaluate the 600 mg dose taken once daily (QD). The selection of the 600 mg dose follows the completion of the analysis of data from a randomized cohort within the Phase 1b study comparing 200 mg and 600 mg in accordance with Project Optimus and reflects alignment with global regulators including the U.S. Food and Drug Administration, the U.K Medicines and Healthcare products Regulatory Agency, and the European Medicines Agency.

In an investor webcast at 8:00 a.m. ET, today, Wednesday, October 22, 2025, Nurix will provide a program update including a review of new preclinical data supporting the potential best-in-class BTK degrader profile of bexobrutideg and discuss the DAYBreak and planned Phase 3 confirmatory studies.

"The initiation of the DAYBreak study marks Nurix’s transition to a pivotal-stage company and a major milestone for bexobrutideg, which our data demonstrate has a potential best-in-class profile," said Arthur T. Sands, M.D., Ph.D., president and chief executive officer of Nurix. "With the DAYBreak study underway, we are advancing the development of bexobrutideg and are one step closer to registration and commercialization."

The DAYBreak study will enroll patients with r/r CLL who have experienced disease progression following treatment with a covalent BTK inhibitor (cBTKi), a BCL-2 inhibitor (BCL-2i), and a non-covalent BTK inhibitor (ncBTKi). The DAYBreak study aims to evaluate bexobrutideg’s potential to address an unmet medical need in this patient population and generate data to support a potential Accelerated Approval submission.

Nurix plans to initiate a randomized confirmatory Phase 3 trial in the first half of 2026 in r/r CLL patients whose disease has previously progressed while receiving a cBTKi. This global Phase 3 confirmatory trial in patients treated in the second line or later setting will compare bexobrutideg monotherapy to an investigator’s choice of pirtobrutinib monotherapy (a ncBTKi), bendamustine + rituximab, or idelalisib + rituximab.

"The favorable safety profile observed at the 600 mg bexobrutideg dose allows us to optimize its therapeutic effect, providing patients the opportunity to regain control of CLL that has progressed or has failed to respond to other therapies," said Paula O’Connor, M.D., chief medical officer of Nurix. "With regulatory alignment, we are advancing a global registrational program intended to address a large unmet need for patients with relapsed or refractory CLL. We look forward to completing this pivotal Phase 2 study and our confirmatory Phase 3 trial as part of our comprehensive development plan designed to provide patients with a much-needed therapeutic alternative.

As an innovator in the field of targeted protein degradation, Nurix has generated significant data to support bexobrutideg’s potential best-in-class BTK degrader profile.

"During our upcoming conference call, we will share highlights from our latest, unpublished preclinical data demonstrating superior degradation potency, broad coverage of clinically relevant BTK mutations, and exquisite selectivity, which together set a high bar for this class of medicines," said Gwenn Hansen, Ph.D., chief scientific officer of Nurix. "These superior attributes strengthen our conviction that bexobrutideg may prove to be a clinically superior medicine for the treatment of patients with CLL and other B-cell driven diseases."

Investor webcast
Nurix will host an investor webcast today, October 22, 2025, at 8:00 a.m. EDT. A live webcast and replay of today’s event will be available on the Investors section of the Nurix website at View Source A copy of the materials to be presented at the Investor Update will be filed in an accompanying Form 8-K filing and may be found at View Source

(Press release, Nurix Therapeutics, OCT 22, 2025, View Source [SID1234656899])

I-Mab To Present Positive Updated Givastomig Monotherapy Data at 2025 AACR-NCI-EORTC Molecular Targets and Cancer Therapeutics Conference on October 23, 2025

On October 22, 2025 I-Mab (NASDAQ: IMAB) (I-Mab or the Company), is a global biotechnology platform company committed to accelerating access to innovative medicines for patients worldwide, reported that updated data from the Phase 1 study (NCT04900818) of givastomig as a monotherapy in heavily pre-treated patients (n=45) with gastroesophageal carcinoma (GEC) will be presented as a "short-talk" at the Triple Meeting on October 23, 2025 in Boston, Massachusetts (Presentation #B016). Givastomig is a bispecific antibody targeting CLDN18.2 (Claudin 18.2) and 4-1BB.

"The Phase 1 givastomig monotherapy data that will be shared at the Triple Meeting continue to demonstrate impressive safety and efficacy, with an 18% ORR in heavily pre-treated gastric cancer patients, with favorable overall safety. These data, showing responses over a dose range from 5 mg/kg Q2W to 18 mg/kg Q3W, further enrich givastomig’s emerging product profile and bolster our confidence that givastomig has the potential to be a best-in-class Claudin18.2-directed therapy across a broad range of CLDN18.2 expression. In Q1 2026, we expect to report topline results from the fully-enrolled Phase 1b dose expansion immune-chemotherapy combination study and initiate a global, randomized Phase 2 combination study. We believe the data from these studies will clearly demonstrate givastomig’s potential to significantly improve the standard of care in the treatment of first line GEC patients with a broad range of Claudin 18.2 expression levels," said Phillip Dennis, MD, PhD, Chief Medical Officer of I-Mab.

"In our experience, givastomig integrates well into the workflow at our center. Based on the monotherapy efficacy across a range of doses and Claudin 18.2 expression levels, and excellent overall safety, givastomig has the potential to be the best-in-class Claudin-directed therapy and combination partner for the treatment of frontline gastric cancer. These follow-up data, plus encouraging initial results from the Phase 1b immune-chemotherapy frontline combination studies, presented earlier this year, give us hope that givastomig treatment can lead to improved treatment outcomes for patients with gastric cancers. We are eager to move forward with the planned Phase 2 study and continue to advance this program," said Samuel J Klempner, MD, Associate Professor of Medicine at Massachusetts General Hospital.

AACR-NCI-EORTC "the Triple Meeting" Conference Information:

Title: Updated Safety, Efficacy and Biomarker Analysis from the Phase I Study of Givastomig, a Novel Claudin 18.2/4-1BB Bispecific Antibody, in Claudin 18.2 Positive Advanced Gastroesophageal Carcinoma (GEC)

Session: Concurrent Session 2: Bispecifics/T-cell Engagers

Speaker: Samuel J. Klempner, MD, Associate Professor of Medicine, Massachusetts General Hospital

Presentation Number: B016

Date and Time: Thursday, October 23, 2025, 6:20 – 6:35 PM ET

Location: Hynes Convention Center

A copy of the Triple Meeting presentation and poster will be available on the Publications and Presentations page of the I-Mab website on October 23, 2025.

Givastomig Phase 1 Monotherapy Updated data Summary GEC (per June 10, 2025 data cut-off):

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Givastomig was well tolerated up to 15 mg/kg Q2W and 18 mg/kg Q3W and continues to show monotherapy activity in heavily pre-treated GEC patients with a wide range of CLDN18.2 expression
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Givastomig may have the ability to target patients with lower CLDN18.2 expression compared with other CLDN18.2 agents
Patients Characteristics:

•
45 GEC patients were dosed with givastomig every two weeks (Q2W) across dose levels of: 5mg/kg (n=7), 8 mg/kg (n=5), 12 mg/kg (n=21), 15 mg/kg (n=6) and 18 mg/kg Q3W (n=6) as of the June 10, 2025 data cutoff
•
Patients had received a median of 3 prior therapies including 74% with a prior PD-L1 inhibitor
Efficacy Results:

•
Confirmed Objective Response Rate (ORR):
o
18% of patients (8/45) achieved a partial response (PR)
▪
5 mg/kg (1/7)
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8 mg/kg (1/5)
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12 mg/kg (4/21)
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15 mg (0/6)
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18 mg/kg Q3W (2/6)
o
Claudin 18.2 expression in responders ranged from 11% (1+, 10%; 2+, 1%) to 100% (2+, 10%; 3+, 90%)
•
The Disease Control Rate (DCR) was 49%, including stable disease (SD) in 14 patients
Follow-up and Biomarker Data:

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2 patients are ongoing (4%), with 1 PR (8 mg/kg) at 33 months (mo), and 1 PR (18 mg/kg Q3W) at 10 mo
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The median progression free survival (mPFS) and median overall survival (mOS) are 2.96 mo (95% CI 1.71-3.91) and 7.49 mo (95% CI 4.96-12.5), respectively

No statistical difference in ORR, DCR, PFS or OS, between CLDN18.2-high (n=21) and CLDN18.2-low patients (n=24): ORR 19% v. 17% (p=1.00), DCR 57% v. 42% (p=0.46), mPFS 3.68 mo v. 1.84 mo, PFS hazard ratio (HR) 0.87 (p=0.67), and mOS 7.49 mo v. 7.49 mo, OS HR 0.88 (p=0.74), respectively
Safety:

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There were no new safety signals identified with longer follow-up
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No dose limiting toxicities were observed
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Common TREAEs (≥15%, any grade/grade 3) included anemia (27%/9%), white blood cell count decrease (22%/7%), nausea (20%/2%), ALT increase (16%/2%) and AST increase (16%/4%)
About Givastomig

Givastomig (TJ033721 / ABL111) is a bispecific antibody targeting Claudin 18.2 (CLDN18.2)-positive tumor cells. It conditionally activates T cells through the 4-1BB signaling pathway in the tumor microenvironment where CLDN18.2 is expressed. Givastomig is being developed for potential treatment of gastric cancer and other Claudin 18.2-positive gastrointestinal malignancies. In Phase 1 trials, givastomig has shown promising anti-tumor activity attributable to a potential synergistic effect of proximal interaction between CLDN18.2 on tumor cells and 4-1BB on T cells in the tumor microenvironment, while minimizing toxicities commonly seen with other 4-1BB agents.

Givastomig is being jointly developed through a global partnership with ABL Bio, in which I-Mab is the lead party and shares worldwide rights, excluding Greater China and South Korea, equally with ABL Bio.

(Press release, I-Mab Biopharma, OCT 22, 2025, View Source [SID1234656898])