Checkpoint Inhibitor Refractory Cancer Market Outlook, Trends And Future Opportunities (2023-2030)

Checkpoint Inhibitor Refractory Cancer Market Outlook, Trends And Future Opportunities (2023-2030)

Checkpoint Inhibitor Refractory Cancer Market, By Mechanism of Action (PD-1 Inhibitors, PD-L1 Inhibitors, CTLA-4 Inhibitors, IDO1 Inhibitors, A2AR Inhibitors, LAG3 Inhibitors, Others), By Cancer Type (Lung Cancer, Melanoma, Renal Cell Carcinoma, Bladder Cancer, Head and Neck Cancer, Hodgkin's Lymphoma, Others), By Route of Administration (Intravenous, Oral, Others), By Distribution Channel (Hospital Pharmacy, Retail Pharmacy, Online Pharmacy), Region (North America, Europe, Asia Pacific, Latin America, Middle East & Africa) The report offers a comprehensive view of the market from supply as well as demand side to help take informed decisions.

  • Published On: Sep 2023
  • Report ID: IDA43
  • Region: Global
  • Format: PDF/EXCEL

The Checkpoint Inhibitor Refractory Cancer Market is poised for remarkable expansion, with projections indicating it will soar to an impressive US$ 19.1 billion by 2030, marking a substantial leap from the US$ 3.4 billion recorded in 2023. This trajectory of growth is underpinned by a robust Compound Annual Growth Rate (CAGR) of 27.8% during the forecast period from 2023 to 2030.

Checkpoint inhibitors, a pivotal category of cancer immunotherapy, serve to activate the immune system, empowering it to identify and target cancer cells. However, a significant challenge arises as many patients inevitably develop resistance to these therapies over time. In this context, refractory cancer denotes disease progression following treatment with conventional approaches like chemotherapy or checkpoint inhibitors. The prevalence of cancer on a global scale, coupled with the escalating instances of acquired resistance, emerges as the driving force propelling growth within the refractory cancer market.

The Checkpoint Inhibitor Refractory Cancer Market revolves around pharmaceutical therapies designed to cater to cancer patients who have ceased responding to initial checkpoint inhibitor treatments. Checkpoint inhibitors represent a pioneering form of immunotherapy, facilitating the immune system's capacity to recognize and combat cancer cells. Refractory cancer, conversely, signifies the progression of the disease following the utilization of standard treatment protocols.

The market's meticulous segmentation strategy incorporates diverse elements such as mechanism of action, cancer type, line of therapy, route of administration, and geographic region. Among these facets, the PD-1/PD-L1 inhibitor segment takes precedence, contributing to the largest market share, surpassing 40% in 2022. PD-1/PD-L1 inhibitors hold the distinction of being the most widely employed class of checkpoint inhibitors. Nevertheless, the development of resistance to these inhibitors is a common occurrence, giving rise to a demand for innovative therapeutic approaches. The advent of novel inhibitors, including IDO1 and A2AR, is making substantial contributions to the growth of this segment.

A recent exemplar of industry advancements lies in Amgen's Lumakras, which received FDA approval in September 2022. It was granted approval for use in combination with Merck's Keytruda, particularly for patients with KRAS-mutated non-small cell lung cancer who had previously undergone checkpoint inhibitor immunotherapy. This development underscores the ongoing pursuit of innovative solutions within the checkpoint inhibitor refractory cancer market, offering renewed hope and therapeutic options for patients grappling with treatment resistance.

Epidemiology Insights:

  • Cancer is a leading cause of death worldwide, with 19.3 million new cases and 10 million cancer deaths in 2020. Lung cancer is the most common cancer type, followed by breast and colorectal cancers.
  • In the US, there were 1.9 million new cancer cases and 609,360 cancer deaths in 2021. The most common cancers are prostate, lung, colorectal and breast.
  • In the EU5, there were over 2.7 million new cases in 2020. Lung, breast, colorectal and prostate cancers were the most common.
  • The rising prevalence of cancer globally is expected to drive demand for newer therapies like checkpoint inhibitors. However, acquired resistance results in disease progression, creating the need for newer treatment approaches.
  • The refractory cancer patient pool is continuously growing as patients develop resistance to initial treatments like chemotherapy, targeted therapy, or immunotherapy. This is creating strong growth opportunities for novel therapies that can overcome resistance.

Market Landscape:

  • There are high unmet needs for effective therapies that can overcome resistance to existing checkpoint inhibitor treatments. Most patients eventually stop responding to initial immunotherapy.
  • Current standard treatments include chemotherapy, targeted therapy using inhibitors like BRAF or EGFR inhibitors, and immunotherapy using PD-1/PD-L1 immune checkpoint inhibitors.
  • Emerging treatment approaches focus on novel inhibitors of pathways beyond PD-1/PD-L1, like LAG3, TIGIT, IDO1, and adenosine A2A receptors. Dual checkpoint inhibitor combinations are also being evaluated.
  • Other novel approaches include CAR T-cell therapy, cancer vaccines, and oncolytic virus therapies to boost immune response against cancers.
  • The market has a mix of big pharma companies with high focus on branded checkpoint inhibitors, along with smaller biotech firms developing niche inhibitors and novel platforms.

Checkpoint Inhibitor Refractory Cancer Market Drivers:

The rising prevalence of cancer globally is a major factor driving growth in the checkpoint inhibitor refractory cancer market. As per WHO estimates, cancer cases are expected to rise by 60% over the next 20 years, from 14 million new cases in 2012 to 22 million cases in 2030. The growing cancer burden is leading to increasing utilization of treatments like chemotherapy, targeted therapy, and immunotherapy. However, a majority of cancer patients develop resistance to these initial treatments over time, creating demand for newer therapies in the refractory setting.

Another key driver is the rising cases of resistance and reduced response to existing checkpoint inhibitor immunotherapies like PD-1, PD-L1 and CTLA-4 inhibitors. Though checkpoint inhibitors revolutionized cancer treatment, most patients eventually become refractory. For instance, in NSCLC, the response rate with anti-PD-1 monotherapy is only around 20%. This is fueling research into novel inhibitors and combination approaches to overcome resistance.

The robust pipeline of investigational therapies that target mechanisms of resistance is also driving market growth. Companies are developing inhibitors of LAG3, TIGIT, IDO1, adenosine A2a receptor, and other immune pathways. Several combination approaches using PD-1/PD-L1 inhibitors along with CTLA4 inhibitors, chemotherapy, or targeted therapies are being explored to improve outcomes.

Growing investments in R&D in this niche area presents growth opportunities. In 2022, Merck acquired cancer immunotherapy developer Imago BioSciences for $1.35 billion to expand its pipeline. Amgen also acquired FivePrime Therapeutics for $1.9 billion to gain its CSF1R inhibitor. The strong interest amongst big pharma companies to expand their oncology pipeline is driving R&D activity.

Checkpoint Inhibitor Refractory Cancer Market Opportunities:

The development of predictive biomarkers to identify patients unlikely to respond to checkpoint inhibitors presents an opportunity to develop targeted therapies. Companies are focused on biomarker-driven clinical trials and companion diagnostic development. For instance, IdentifyMets is developing a gene expression test to identify cancer patients unlikely to respond to Keytruda.

Novel platforms like mRNA vaccines, oncolytic viruses, bispecific antibodies and CAR T-cell therapies hold promise in overcoming resistance mechanisms. Moderna recently started Phase 1/2 trials of its personalized cancer vaccine in combination with Keytruda for high-risk melanoma. Oncolytic viruses like Amgen’s T-Vx-ND are also being evaluated to boost anti-tumor immunity.

Emerging evidence that gut microbiome impacts response to checkpoint inhibitors offers potential opportunities. Multiple research groups are exploring microbiome modulating therapies to enhance immunotherapy efficacy. Early results from microbiome editing company Seraxis in melanoma are encouraging. Similar approaches could help overcome resistance.

The rising popularity of dual checkpoint inhibitor combinations presents an opportunity for long-term market growth. Though associated with higher toxicity, combinations like Opdivo and Yervoy have shown superior efficacy in difficult-to-treat cancers. Dual combinations targeting various immune pathways are a promising approach.

Key Insights


The market size in 2023

US$ 3.4 Bn

CAGR (2023 - 2030)


The revenue forecast in 2030

US$ 19.1 Bn

Base year for estimation


Historical data


Forecast period


Quantitative units

Revenue in USD Million, and CAGR from 2021 to 2030

Market segments

  • By Mechanism of Action: PD-1 Inhibitors, PD-L1 Inhibitors, CTLA-4 Inhibitors, IDO1 Inhibitors, A2AR Inhibitors, LAG3 Inhibitors, Others
  • By Cancer Type: Lung Cancer, Melanoma, Renal Cell Carcinoma, Bladder Cancer, Head and Neck Cancer, Hodgkin's Lymphoma, Others
  • By Route of Administration: Intravenous, Oral, Others
  • By Distribution Channel: Hospital Pharmacy, Retail Pharmacy, Online Pharmacy

Regional scope

North America, Europe, Asia Pacific, Latin America, Middle East, and Africa

Market Drivers

  • Rising prevalence of cancer globally
  • Increasing cases of resistance to checkpoint inhibitors
  • Robust pipeline of investigational therapies
  • Growing investments in R&D in the refractory cancer space

Market Restraints

  • High costs associated with emerging experimental therapies
  • Added toxicity risks with combination immunotherapies

Competitive Landscape

Merck, Amgen, AstraZeneca, Roche, Pfizer, Novartis, AbbVie, GlaxoSmithKline, Sanofi, Gilead Sciences, Takeda, Bristol-Myers Squibb, Merck KGaA, Regeneron, Moderna, Johnson & Johnson, Eli Lilly, Bayer, Daiichi Sankyo, Eisai

Checkpoint Inhibitor Refractory Cancer Market Trends:

A key trend is the development of therapies with novel mechanisms of action compared to existing PD-1/PD-L1 inhibitors. Targeting non-redundant pathways that mediate resistance is of growing interest. Examples include TIGIT inhibitors being developed by Genentech and Arcus Biosciences.

Leveraging real-world data and AI to better understand resistance mechanisms and predictors of response is an important trend. In 2021, GlaxoSmithKline acquired AI startup Exscientia which is using AI platforms for oncology drug discovery. Real-world data improves understanding of treatment patterns.

Biopharma companies are increasingly pursuing strategic collaborations and acquisitions to fast-track novel therapies in the refractory cancer space. Gilead-Galapagos, Bristol Myers Squibb-Dragonfly Therapeutics, Roche-Regeneron are some partnerships seen in recent years in this niche space.

Due to the disappointing efficacy of monotherapies, combination regimens are gaining prominence. Combining PD-1 inhibitors with CTLA-4 inhibitors or chemotherapy has shown clinical benefit. Many ongoing clinical studies are assessing novel doublet and triplet combinations.

Checkpoint Inhibitor Refractory Cancer Market Restraints:

A key factor hampering growth is the high costs associated with the development and approval of emerging experimental therapies, coupled with hesitancy among payers. For instance, the ICER value for a new lung cancer immunotherapy could be ~$200,000 per QALY.

The added toxicity risks associated with combination immunotherapies using multiple checkpoint inhibitors acts as a market restraint. In studies, over 55% patients experienced high-grade adverse effects with Opdivo-Yervoy versus only 16.3% with Opdivo alone.

The lack of definitive biomarkers to predict patient response to emerging investigational therapies is a challenge. Currently, biomarkers like TMB and PD-L1 expression have limited sensitivity. Better predictive biomarkers are required for more targeted use.

The limited efficacy offered by new experimental agents in early-phase studies makes it challenging to demonstrate superiority over existing gold-standard therapies, restricting rapid approval and adoption.

Recent Developments:


Involved Company

Gilead’s $21Bn Acquisition of Immunomedics Gilead Sciences


Merck’s $2.75Bn Acquisition of VelosBio Merck


Roche’s Collaboration with Regeneron for Immune Roche

Regeneron Checkpoint Inhibitors

Product launch:

  • In June 2021, Merck launched Keytruda in combination Merck with chemotherapy for first-line treatment of locally advanced or metastatic esophageal and gastroesophageal cancers. This expanded Keytruda's addressable patient population.
  • In March 2022, AstraZeneca and Daiichi’s Enhertu AstraZeneca, Daiichi Sankyo was granted accelerated US FDA approval for unresectable or metastatic HER2-mutant non-small cell lung cancer following prior systemic therapy.
  • In September 2021, BeiGene announced China NMPA BeiGene
    approval of tislelizumab in combination with chemotherapy as first-line treatment for patients with advanced squamous non-small cell lung cancer.


  • In September 2020, Gilead completed the Gilead Sciences, Immunomedics acquisition of Immunomedics for $21 billion. This allowed Gilead to gain rights to Trodelvy, an antibody-drug conjugate for metastatic triple-negative breast cancer.
  • In November 2021, Pfizer acquired Trillium Pfizer, Trillium Therapeutics Therapeutics for $2.3 billion to boost its immuno-oncology portfolio with CD47 blocking therapies.

Checkpoint Inhibitor Refractory Cancer Market Regional Insights:

The Checkpoint Inhibitor Refractory Cancer Market exhibits distinct regional trends and drivers, influenced by factors such as cancer prevalence, research endeavors, product launches, and the presence of key industry players. A closer look at regional insights reveals key growth dynamics.

  • North America: Pioneering Advancements North America is poised to dominate the Checkpoint Inhibitor Refractory Cancer Market, commanding a substantial market share of over 42% in 2023. This region's leadership is attributed to several factors, including a high prevalence of cancer cases, continuous launches of new products, and the significant presence of key players in the industry. North America's commitment to advancing cancer treatment options positions it at the forefront of the market.
  • Europe: A Strong Contender Europe solidifies its position as the second-largest market for checkpoint inhibitor refractory cancer, contributing a noteworthy market share of over 32% in 2023. The growth in this region is driven by an increasing incidence of cancer and a rising focus on research to develop novel therapies. Europe's dedication to advancing the field of cancer treatment underscores its significance in the market.
  • Asia Pacific: A Thriving Frontier The Asia Pacific market emerges as the fastest-growing hub for the Checkpoint Inhibitor Refractory Cancer Market, exhibiting an impressive Compound Annual Growth Rate (CAGR) of over 28% during the forecast period. This growth surge is attributed to expanding Research and Development (R&D) expenditure and the strategic focus of global companies on this region. Asia Pacific captures a market share of 15.7%, representing its status as a thriving frontier in cancer treatment.
  • Other Regions: Contributing to Global Growth While holding smaller market shares, Latin America and the Middle East & Africa regions play integral roles in the global Checkpoint Inhibitor Refractory Cancer Market. Latin America contributes with a market share of 5.8%, while the Middle East & Africa region accounts for 5.2%. These regions, though relatively smaller in market size, contribute to the global landscape and offer potential avenues for growth.

In summary, regional disparities in cancer prevalence, research focus, and industry presence significantly influence the dynamics of the Checkpoint Inhibitor Refractory Cancer Market. North America leads the way with pioneering advancements, Europe maintains its position as a formidable contender, and the Asia Pacific region emerges as a thriving frontier. Additionally, Latin America and the Middle East & Africa continue to make valuable contributions to the global market landscape.

Checkpoint Inhibitor Refractory Cancer Market Segmentation:

By Mechanism of Action

  • PD-1 Inhibitors
  • PD-L1 Inhibitors
  • CTLA-4 Inhibitors
  • IDO1 Inhibitors
  • A2AR Inhibitors
  • LAG3 Inhibitors
  • Others

By Cancer Type

  • Lung Cancer
  • Melanoma
  • Renal Cell Carcinoma
  • Bladder Cancer
  • Head and Neck Cancer
  • Hodgkin's Lymphoma
  • Others

By Route of Administration

  • Intravenous
  • Oral
  • Others

By Distribution Channel

  • Hospital Pharmacy
  • Retail Pharmacy
  • Online Pharmacy

By Region

  • North America
    • U.S.
    • Canada
  • Europe
    • Germany
    • U.K.
    • Spain
    • France
    • Italy
    • Russia
    • Rest of Europe
  • Asia Pacific
  • China
  • India
  • Japan
  • Australia
  • South Korea
  • Rest of Asia Pacific
  • Latin America
    • Brazil
    • Argentina
    • Mexico
    • Rest of Latin America
  • Middle East & Africa
  • GCC Countries
  • Israel,
  • South Africa
  • North Africa
  • Central Africa
  • Rest of the Middle East

Top companies in the Checkpoint Inhibitor Refractory Cancer Market:

  • Merck
  • Amgen
  • AstraZeneca
  • Roche
  • Pfizer
  • Novartis
  • AbbVie
  • GlaxoSmithKline
  • Sanofi
  • Gilead Sciences
  • Takeda
  • Bristol-Myers Squibb
  • Merck KGaA
  • Regeneron
  • Moderna
  • Johnson & Johnson
  • Eli Lilly
  • Bayer
  • Daiichi Sankyo
  • Eisai

Frequently Asked Questions

The current market size of the checkpoint inhibitor refractory cancer market is estimated at USD 3.4 billion in 2023.

Increasing cancer prevalence globally, rising cases of resistance to checkpoint inhibitors, Strong R&D focus and pipeline products, Advances in combination therapies, Emergence of niche inhibitors and novel platforms, Growing diagnostic capabilities

Major players in Checkpoint Inhibitor Refractory Cancer Market: Merck, Amgen, AstraZeneca, Roche, Pfizer, Novartis, AbbVie, GlaxoSmithKline, Sanofi, Gilead Sciences, Takeda, Bristol-Myers Squibb, Merck KGaA, Regeneron, Moderna, Johnson & Johnson, Eli Lilly, Bayer, Daiichi Sankyo, Eisai

CAGR of 27.8% and market size of USD 19.1 billion by 2030