HER2-Negative Metastatic Breast Cancer Pipeline Insight, 2025: Immunotherapy and ADCs Drive Innovation Across HR+ and TNBC Subtypes | DelveInsight

The HER2-negative metastatic breast cancer (MBC) landscape is rapidly evolving, with over 50 candidates in clinical development across hormone receptor-positive (HR+) and triple-negative breast cancer (TNBC) subtypes. Novel approaches-including antibody-drug conjugates (ADCs), immune checkpoint inhibitors, AKT inhibitors, PARP inhibitors, and TROP2-targeted therapies-are at the forefront of innovation as developers pursue more durable, biomarker-driven treatment strategies.
The HER2-negative metastatic breast cancer (MBC) landscape is rapidly evolving, with over 50 candidates in clinical development across hormone receptor-positive (HR+) and triple-negative breast cancer (TNBC) subtypes. Novel approaches-including antibody-drug conjugates (ADCs), immune checkpoint inhibitors, AKT inhibitors, PARP inhibitors, and TROP2-targeted therapies-are at the forefront of innovation as developers pursue more durable, biomarker-driven treatment strategies.

DelveInsight's "HER2-Negative Metastatic Breast Cancer - Pipeline Insight, 2025 [https://www.delveinsight.com/report-store/her2-negative-metastatic-breast-cancer-pipeline-insight?utm_source=abnewswire&utm_medium=pressrelease&utm_campaign=jpr]" delivers an in-depth analysis of the dynamic therapeutic pipeline for HER2-negative MBC, which represents the majority of all breast cancer cases. HR+ is the most prevalent subtype, often treated with endocrine therapies, while TNBC remains a challenging, aggressive disease with fewer effective long-term options. Sacituzumab govitecan (Trodelvy), the first ADC approved for metastatic TNBC, is now being evaluated in HR+ settings, expanding its potential reach. Datopotamab deruxtecan, another TROP2-directed ADC, is progressing through Phase III trials in both HR+ and TNBC cohorts and is considered a next-generation competitor in the class.

Meanwhile, AstraZeneca's capivasertib, an AKT inhibitor, has shown promise in HR+ MBC when combined with endocrine agents, as demonstrated in the pivotal CAPItello-291 trial. Immunotherapies like pembrolizumab (Keytruda) and atezolizumab continue to play a role in PD-L1+ TNBC, with ongoing evaluations in earlier-line settings and in combination with chemotherapy, ADCs, or targeted agents.

Biomarker-led approaches, including genomic profiling, circulating tumor DNA (ctDNA), and immune signatures, are shaping trial designs and patient stratification, especially as resistance to endocrine or chemotherapies emerges. Developers are also leveraging ADC platforms and bispecific antibodies to improve drug delivery specificity and reduce systemic toxicity, particularly in the TNBC population.

As 2025 progresses, the pipeline is shifting from traditional chemotherapy-based regimens toward personalized, mechanism-based therapies with higher efficacy and tolerability. Global trials are enrolling rapidly, aided by patient advocacy, expanded access initiatives, and regulatory mechanisms such as fast track, breakthrough designation, and accelerated approvals.

The future of HER2-negative MBC therapy lies in precision oncology and rational drug combinations, offering renewed hope for patients with both HR+ and TNBC subtypes. With more than 100 therapies in development and several late-stage candidates poised for regulatory milestones, this space is on the brink of a significant therapeutic transformation.

Interested in learning more about the current treatment landscape and the key drivers shaping the HER2 HER2-negative metastatic Breast Cancer pipeline? Click here [https://www.delveinsight.com/report-store/her2-negative-metastatic-breast-cancer-pipeline-insight?utm_source=abnewswire&utm_medium=pressrelease&utm_campaign=jpr]

Key Takeaways from the HER2 Negative Metastatic Breast Cancer Pipeline Report

- DelveInsight's HER2 Negative Metastatic Breast Cancer pipeline analysis depicts a strong space with 50+ active players working to develop 50+ pipeline drugs for HER2 Negative Metastatic Breast Cancer treatment.

- The leading HER2 Negative Metastatic Breast Cancer companies include BeiGene, Context Therapeutics, Astex Pharmaceuticals, Eisai Inc., AstraZeneca, Dantari, Inc., and others are evaluating their lead assets to improve the HER2 Negative Metastatic Breast Cancer treatment landscape.

- Key HER2 HER2-negative metastatic Breast Cancer pipeline therapies in various stages of development include Pamiparib, Onapristone, ASTX-727, Durvalumab, DAN-222, and others.

- In July 2025, Imagion Biosystems (ASX: IBX), a company focused on enhancing healthcare outcomes through early cancer detection using its proprietary MagSense HER2 imaging technology, announced an update for shareholders on its upcoming Phase 2 HER2 breast cancer clinical trial planned in the U.S.

- In June 2025, results from the Phase III OASIS-4 study showed that elinzanetant significantly reduced moderate to severe vasomotor symptoms (VMS) in women undergoing endocrine therapy for hormone receptor-positive (HR+) breast cancer. Statistically significant improvements were also seen in sleep disturbances, menopause-related quality of life, and VMS severity. The findings were presented at ASCO 2025 and published in the New England Journal of Medicine. OASIS-4 is the first global Phase III trial to evaluate elinzanetant for VMS linked to endocrine therapy in HR+ breast cancer.

- In April 2025, AstraZeneca and Daiichi Sankyo announced positive high-level results from the planned interim analysis of the DESTINY-Breast09 Phase III trial. The trial demonstrated that Enhertu (trastuzumab deruxtecan) in combination with pertuzumab provided a statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared to the current 1st-line standard of care regimen of taxane, trastuzumab, and pertuzumab (THP) for patients with HER2-positive metastatic breast cancer. This marks the first trial in over a decade to show superior efficacy across a broad HER2-positive metastatic patient population.

- In April 2025, AstraZeneca and Daiichi Sankyo's ENHERTU (trastuzumab deruxtecan) was approved in the EU as monotherapy for adults with unresectable or metastatic HR-positive, HER2-low/ultralow breast cancer, after at least one endocrine therapy and when further endocrine therapy is unsuitable.

- In March 2025, the FDA granted orphan drug designation to NERLYNX (neratinib) for breast cancer patients with brain metastases. Neratinib is a tyrosine kinase inhibitor approved for extended adjuvant treatment of HER2-positive breast cancer after trastuzumab therapy.

- In January 2025, the FDA approved AstraZeneca's DATROWAY (datopotamab deruxtecan or Dato-DXd) for adults with unresectable or metastatic HR-positive, HER2-negative breast cancer who have previously received endocrine therapy and chemotherapy.

Request a sample and discover the recent breakthroughs happening in the HER2-negative metastatic Breast Cancer pipeline landscape [https://www.delveinsight.com/report-store/her2-negative-metastatic-breast-cancer-pipeline-insight?utm_source=abnewswire&utm_medium=pressrelease&utm_campaign=jpr].

HER2 Negative Metastatic Breast Cancer Overview

HER2 Negative Metastatic Breast Cancer (MBC) is a subtype of breast cancer where the cancer cells lack overexpression of the human epidermal growth factor receptor 2 (HER2) protein. This form of metastatic breast cancer tends to have different treatment options and prognosis compared to HER2-positive cases. Patients with HER2-negative MBC often rely on hormone therapies, chemotherapy, and emerging targeted treatments. The absence of HER2 makes therapies like trastuzumab ineffective, underscoring the need for alternative therapeutic strategies to manage disease progression and improve patient outcomes.

Find out more about HER2 Negative Metastatic Breast Cancer medication at https://www.delveinsight.com/report-store/her2-negative-metastatic-breast-cancer-pipeline-insight [https://www.delveinsight.com/report-store/her2-negative-metastatic-breast-cancer-pipeline-insight?utm_source=abnewswire&utm_medium=pressrelease&utm_campaign=jpr]

HER2 Negative Metastatic Breast Cancer Treatment Analysis: Drug Profile

Pamiparib: BeiGene

Pamiparib is a selective small-molecule inhibitor targeting PARP1 and PARP2 enzymes, under investigation as both a monotherapy and in combination treatments for various solid tumors. It stands out from other PARP inhibitors due to its ability to penetrate the brain, higher selectivity, strong DNA-trapping effects, and good oral bioavailability, as shown in preclinical studies. Pamiparib is currently in Phase II clinical trials for the treatment of HER2-negative metastatic breast cancer.

Onapristone: Context Therapeutics

ONA-XR, an extended-release form of onapristone, is an experimental drug that blocks progesterone signaling by preventing the progesterone receptor (PR) from binding to its partner. As the only known full PR antagonist, it targets PR-positive cancers-an area with no currently approved selective therapies. Preclinical and clinical evidence indicate that ONA-XR inhibits PR binding to chromatin, reduces cancer stem cell activity, and blocks immune evasion. It is presently being evaluated in multiple Phase II and Phase 0 trials for primary and metastatic breast, ovarian, and endometrial cancers, including HER2-negative metastatic breast cancer.

HER2 Negative Metastatic Breast Cancer Therapeutics Assessment

By Product Type

- Mono

- Combination

- Mono/Combination.

By Stage

- Late-stage products (Phase III)

- Mid-stage products (Phase II)

- Early-stage product (Phase I) along with the details of

- Pre-clinical and Discovery stage candidates

- Discontinued & Inactive candidates

By Route of Administration

- Intra-articular

- Intraocular

- Intrathecal

- Intravenous

- Ophthalmic

- Oral

- Parenteral

- Subcutaneous

- Topical

- Transdermal

By Molecule Type

- Oligonucleotide

- Peptide

- Small molecule

Scope of the HER2 Negative Metastatic Breast Cancer Pipeline Report

- Coverage: Global

- Key HER2 Negative Metastatic Breast Cancer Companies: BeiGene, Context Therapeutics, Astex Pharmaceuticals, Eisai Inc., AstraZeneca, Dantari, Inc., and others.

- Key HER2 Negative Metastatic Breast Cancer Pipeline Therapies: Pamiparib, Onapristone, ASTX-727, Durvalumab, DAN-222, and others.

Explore detailed insights on drugs used in the treatment of HER2-negative metastatic Breast Cancer here [https://www.delveinsight.com/report-store/her2-negative-metastatic-breast-cancer-pipeline-insight?utm_source=abnewswire&utm_medium=pressrelease&utm_campaign=jpr].

Table of Contents

1. Introduction

2. Executive Summary

3. HER2 Negative Metastatic Breast Cancer Pipeline: Overview

4. Analytical Perspective In-depth Commercial Assessment

5. HER2 Negative Metastatic Breast Cancer Pipeline Therapeutics

6. HER2 Negative Metastatic Breast Cancer Pipeline: Late-Stage Products (Phase III)

7. HER2 Negative Metastatic Breast Cancer Pipeline: Mid-Stage Products (Phase II)

8. HER2 Negative Metastatic Breast Cancer Pipeline: Early Stage Products (Phase I)

9. Therapeutic Assessment

10. Inactive Products

11. Company-University Collaborations (Licensing/Partnering) Analysis

12. Key Companies

13. Key Products

14. Unmet Needs

15. Market Drivers and Barriers

16. Future Perspectives and Conclusion

17. Analyst Views

18. Appendix

About DelveInsight

DelveInsight is a leading Business Consultant and Market Research firm focused exclusively on life sciences. It supports Pharma companies by providing comprehensive end-to-end solutions to improve their performance. Get hassle-free access to all the healthcare and pharma market research reports through our subscription-based platform, PharmDelve.

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