CLINICAL TRIALS PROFILE FOR ALPELISIB

All Clinical Trials for alpelisib

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT01602315 ↗	A Phase Ib/II Study of BYL719 and Cetuximab in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma	Terminated	Novartis Pharmaceuticals	Phase 1/Phase 2	2012-11-12	This was a multi-center, open-label, Phase Ib dose escalation /Phase II study in recurrent or metastatic head and neck squamous cell carcinoma (RM HNSCC) patients considered to be resistant, ineligible or intolerant to platinum-based chemotherapy. The Phase Ib included three arms. Three different methods of administration and two different BYL719 formulations were studied to determine the MTD and/or RP2D of BYL719 in combination with cetuximab: Arm A - film-coated whole tablets were orally administered to patients who were able to swallow the tablets; Arm B - a drinkable suspension prepared from crushed film-coated tablets was administered orally to patients with swallowing dysfunction Arm C - a suspension from a dispersible tablet administered via G-tube, in patients with swallowing dysfunction. Arm C was used to investigate the pharmacokinetics (PK), compared to Arm A (film coated tablet), and safety of the dispersible tablet of the dispersible tablet formulation of BYL719. The Phase II investigated the clinical efficacy of BYL719 and consisted of an open label, randomized Phase II part investigating BYL719 in combination with cetuximab compared to cetuximab alone in patients resistant or intolerant to platinum and naïve to cetuximab (Scheme 1: Arm 1 and Arm 2), and a non-randomized Phase II part Scheme 2: Arm 3. In addition, patients who experienced disease progression in Arm 2 (cetuximab) were allowed to switch to the combination regimen (cross-over, Arm 2B). The safety of the BYL719 in combination with cetuximab was also further characterized in Arms 1, 2B and 3. Patients were treated until progression of disease), unacceptable toxicity, or withdrawal of informed consent, whichever occurred first (except for phase II Arm 2 had the opportunity to crossover to the combination treatment (Arm 2B). In the follow-up period all patients had to complete the safety follow-up assessments within 30 days after the last dose of the study treatment. Patients who did not have disease progression at the time of discontinuation of study treatment were radiologically followed for disease status until disease progression, initiation of subsequent anticancer therapies, or death, whichever occurred first. In addition, all patients enrolled in Phase II were followed for survival.
NCT01708161 ↗	A Phase Ib/II Study of the Combination of BYL719 Plus AMG 479 in Adult Patients With Selected Solid Tumors	Terminated	NantCell, Inc.	Phase 1/Phase 2	2012-11-27	This was a multi-center, open-label, phase Ib/II study. The aim of the phase Ib part was to estimate the MTD(s) and/or identify the recommended phase II dose(s) (RP2Ds) for the combination of BYL719 and AMG 479 (ganitumab), followed by the phase II part to assess the clinical efficacy and to further assess the safety of the combination in selected patient populations. Patients were to be treated until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. All patients were to be followed up. At a minimum, patients must have completed the safety follow-up assessments 30 days after the last dose of the study treatment.
NCT01708161 ↗	A Phase Ib/II Study of the Combination of BYL719 Plus AMG 479 in Adult Patients With Selected Solid Tumors	Terminated	Novartis Pharmaceuticals	Phase 1/Phase 2	2012-11-27	This was a multi-center, open-label, phase Ib/II study. The aim of the phase Ib part was to estimate the MTD(s) and/or identify the recommended phase II dose(s) (RP2Ds) for the combination of BYL719 and AMG 479 (ganitumab), followed by the phase II part to assess the clinical efficacy and to further assess the safety of the combination in selected patient populations. Patients were to be treated until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. All patients were to be followed up. At a minimum, patients must have completed the safety follow-up assessments 30 days after the last dose of the study treatment.
NCT01822613 ↗	Study of Safety & Efficacy of the Combination of LJM716 & BYL719 in Patients With Previously Treated Esophageal Squamous Cell Carcinoma (ESCC)	Completed	Novartis Pharmaceuticals	Phase 1	2013-07-26	To study the safety and efficacy of the combination of LJM716 and BYL719 against currently available treatments of physician's choice in previously treated esophageal squamous cell carcinoma patients.
NCT01923168 ↗	Study of Letrozole With or Without BYL719 or Buparlisib, for the Neoadjuvant Treatment of Postmenopausal Women	Completed	Novartis Pharmaceuticals	Phase 2	2014-03-11	The purpose of the study was to determine whether treatment with a PI3K inhibitor plus letrozole led to an increase in pathologic clinical response and Objective Response Rate compared to treatment with placebo plus letrozole in patients with Breast cancer.

Clinical Trial Conditions for alpelisib

Condition Name

Condition Name for alpelisib
Intervention	Trials
Breast Cancer	20
Metastatic Breast Cancer	10
Advanced Breast Cancer	8
HER2-negative Breast Cancer	7

Condition MeSH

Condition MeSH for alpelisib
Intervention	Trials
Breast Neoplasms	44
Neoplasms	8
Carcinoma	8
Carcinoma, Squamous Cell	6

Clinical Trial Locations for alpelisib

Trials by Country

Trials by Country for alpelisib
Location	Trials
United States	196
Italy	79
Spain	44
China	36
Japan	26

Trials by US State

Trials by US State for alpelisib
Location	Trials
Texas	15
New York	15
California	15
Massachusetts	11
Missouri	10

Clinical Trial Progress for alpelisib

Clinical Trial Phase

Clinical Trial Phase for alpelisib
Clinical Trial Phase	Trials
PHASE2	4
PHASE1	2
Phase 4	1

Clinical Trial Status

Clinical Trial Status for alpelisib
Clinical Trial Phase	Trials
Recruiting	33
Not yet recruiting	22
Completed	5

Clinical Trial Sponsors for alpelisib

Sponsor Name

Sponsor Name for alpelisib
Sponsor	Trials
Novartis Pharmaceuticals	31
Novartis	9
National Cancer Institute (NCI)	4

Sponsor Type

Sponsor Type for alpelisib
Sponsor	Trials
Industry	69
Other	48
NIH	5

Clinical Trials Update, Market Analysis, and Projection for Alpelisib

Last updated: October 28, 2025

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Introduction

Alpelisib, marketed under the brand name Piqray, is an oral phosphatidylinositol-3-kinase (PI3K) alpha-specific inhibitor developed by Novartis. It has garnered significant attention in oncology due to its targeted mechanism in treating hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer harboring PIK3CA mutations. As precision medicine gains prominence, Alpelisib’s clinical development, regulatory status, and market positioning form vital components for stakeholders aiming to capitalize on the evolving landscape of targeted cancer therapies.

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Clinical Trials Update

Regulatory Approvals and Current Indications

Alpelisib received FDA approval in May 2019 for use in combination with fulvestrant for postmenopausal women and adult men with HR-positive, HER2-negative, PIK3CA-mutated advanced or metastatic breast cancer following progression on or after endocrine therapy — marking it as the first PI3K inhibitor approved explicitly for a genetically defined breast cancer subset [1]. The European Medicines Agency (EMA) followed suit in June 2020, approving Piqray with similar indications.

Ongoing and Recent Trials

The next wave of Alpelisib research centers on expanding its therapeutic potential. The SOLAR-1 trial remains the pivotal study underpinning its approval, assessing efficacy and safety in PIK3CA-mutant breast cancer [2]. Recent updates include:

• SOLAR-2: A phase III trial evaluating Alpelisib plus fulvestrant versus placebo in a broader population, including PIK3CA-mutant advanced breast cancers in the second-line setting. Results are anticipated to further inform clinical utility and possibly expand indications.
• Combination studies: Novartis is exploring combinations of Alpelisib with other targeted therapies, including CDK4/6 inhibitors and immunotherapies, to enhance efficacy and overcome resistance mechanisms.
• Alternative cancer types: Phase I/II trials investigating Alpelisib in PIK3CA-mutant head and neck squamous cell carcinomas, and other solid tumors, are ongoing, seeking to broaden its application spectrum.

Safety and Resistance Profiles

Adverse events noted from clinical trials include hyperglycemia (most common), rash, diarrhea, and fatigue. Managing metabolic side effects remains a clinical consideration; hence, ongoing studies focus on optimizing safety profiles [3]. Resistance mechanisms, primarily via secondary mutations or pathway reactivation, are being investigated to guide subsequent combination strategies.

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Market Analysis

Market Size and Dynamics

The breast cancer therapeutic market is substantial, with global revenues reaching over USD 20 billion annually. Alpelisib’s targeted approach positions it within the niche of precision oncology, a rapidly expanding segment. The PI3K inhibitor class, though limited in approved agents, has significant growth potential due to the increasing identification of PIK3CA mutations across diverse tumor types.

Competitive Landscape

Currently, Alpelisib faces limited competition within its indication:

• Buparlisib (BKM120): A pan-PI3K inhibitor with similar targets but less selective, facing setbacks due to toxicity.
• Taselisib and others: in development, but none have achieved FDA approval yet.

The specificity for PIK3CA mutations gives Alpelisib a competitive advantage, solidifying its market position.

Market Penetration and Adoption Factors

Adoption remains driven by:

• Diagnostic testing: Routine PIK3CA mutation testing (via NGS panels) is essential for identifying eligible patients, facilitated by increasing availability and decreasing costs.
• Combination regimens: Clinician preference for combination therapy to improve efficacy.
• Safety management: Effective management of hyperglycemia and other side effects influences prescribing patterns.

Future Market Growth

Projections estimate the global Alpelisib market to grow at a compound annual growth rate (CAGR) of approximately 15-20% from 2023 to 2030, driven by:

• Increased prevalence of PIK3CA mutations in breast and other cancers.
• Rising adoption of genomic testing.
• Ongoing clinical trials supporting label expansion.
• Expansion into earlier-line settings and other solid tumors.

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Market Projection and Strategic Outlook

Considering current clinical trial data, regulatory landscape, and competitive factors, Alpelisib’s market outlook appears optimistic:

• Short-term (2023-2025): Growth driven by current approvals and increasing diagnostic penetration.
• Mid-term (2025-2028): Potential expansion into neoadjuvant and adjuvant settings, pending positive trial outcomes.
• Long-term (2028+): Broader indication spectrum, including other PIK3CA-driven malignancies, augmented use in combination therapies, and possibly developing resistance management.

With Novartis’s continued investment in clinical research and strategic partnerships, Alpelisib is positioned to retain its leadership role in a niche but expanding targeted therapy market.

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Key Challenges and Considerations

• Toxicity management: Hyperglycemia remains a pivotal limiting factor, requiring careful patient selection and management strategies.
• Biomarker testing infrastructure: Widespread implementation of PIK3CA mutation testing is necessary for optimal patient stratification.
• Competitive development: Future pipeline agents and combination regimens may alter the competitive landscape.

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Conclusion

Alpelisib has established a solid foothold in precision breast oncology, with ongoing trials poised to expand its indications and clinical utility. Market prospects are robust, fueled by increasing adoption of molecular diagnostics, positive clinical outcomes, and strategic combination approaches. Navigating safety concerns and competitive advancements will determine its long-term market sustainability. Stakeholders should closely monitor ongoing research and evolving regulatory pathways to leverage emerging opportunities effectively.

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Key Takeaways

• Regulatory status: Alpelisib is FDA and EMA-approved for PIK3CA-mutant HR-positive, HER2-negative advanced breast cancer.
• Clinical pipeline: Ongoing trials aim to expand its utility across cancer types and combination therapies.
• Market potential: The targeted PI3K inhibitor market is expected to grow at a CAGR of 15-20%, with Alpelisib leading its niche.
• Adoption drivers: Genomic testing, combination therapy research, and management of adverse effects are critical factors.
• Future outlook: Broader indications, early-line use, and combination strategies are expected to sustain growth prospects.

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FAQs

1. What is the primary mechanism of action of Alpelisib?
   Alpelisib specifically inhibits the PI3K alpha isoform, a key enzyme in cell growth and survival pathways, notably activated in PIK3CA-mutant cancers.

2. Which patient population is most likely to benefit from Alpelisib?
   Postmenopausal women and adult men with HR-positive, HER2-negative PIK3CA-mutant advanced breast cancer, particularly after progression on endocrine therapy.

3. Are there any significant safety concerns associated with Alpelisib?
   The most common adverse event is hyperglycemia, which requires proactive management. Other side effects include rash, diarrhea, and fatigue.

4. Is Alpelisib being investigated for other cancers?
   Yes, ongoing trials are exploring its efficacy in PIK3CA-mutant head and neck cancers, ovarian cancers, and other solid tumors.

5. What are the key factors influencing Alpelisib’s market growth?
   Increased molecular testing, clinical validation in broader indications, combination therapy strategies, and management of adverse effects.

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References

[1] U.S. Food and Drug Administration. (2019). FDA Approves Novartis’ Piqray for Breast Cancer.
[2] Basel, Switzerland: Novartis. (2022). SOLAR-1 Trial Results Summary.
[3] Juric D, et al. (2020). Safety and management of hyperglycemia in alpelisib trials. Cancer.

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This comprehensive analysis aims to support strategic decision-making for pharmaceutical companies, investors, clinicians, and policymakers invested in Alpelisib’s evolving landscape.