Candel Therapeutics Reports Both Prolonged Median Overall Survival and Long Tail of Survival in Phase 2a Clinical Trial of CAN-2409 in Advanced Non-Small Cell Lung Cancer (NSCLC) Patients Non-Responsive to Immune Checkpoint Inhibitor (ICI) Treatment
Candel Therapeutics reported final survival data from its Phase 2a clinical trial of CAN-2409 in advanced Non-Small Cell Lung Cancer (NSCLC) patients who failed to respond to immune checkpoint inhibitor (ICI) treatment. The study showed remarkable results with median overall survival (mOS) of 24.5 months in the evaluable patient population, significantly exceeding the standard care outcomes.
Key findings include:
- 21.5 months mOS in patients with progressive disease despite ICI therapy, compared to 9.8-11.8 months with standard docetaxel chemotherapy
- 37% of patients survived beyond 2 years after CAN-2409 administration
- 69% of patients showed regression in uninjected tumors (abscopal effect)
- Non-squamous NSCLC patients showed superior outcomes with 25.4 months mOS
The treatment maintained a favorable safety profile throughout the extended follow-up period. The FDA has granted Fast Track Designation for CAN-2409 in combination with ICI treatment for stage III/IV NSCLC patients resistant to first-line PD-(L)1 inhibitor therapy.
Candel Therapeutics ha riportato i dati finali di sopravvivenza dal suo studio clinico di fase 2a su CAN-2409 in pazienti con carcinoma polmonare non a piccole cellule (NSCLC) avanzato che non hanno risposto al trattamento con inibitori dei checkpoint immunitari (ICI). Lo studio ha mostrato risultati notevoli con una sopravvivenza globale mediana (mOS) di 24,5 mesi nella popolazione di pazienti valutabile, superando significativamente i risultati delle cure standard.
I risultati chiave includono:
- 21,5 mesi di mOS nei pazienti con malattia progressiva nonostante la terapia ICI, rispetto a 9,8-11,8 mesi con la chemioterapia standard con docetaxel
- Il 37% dei pazienti è sopravvissuto oltre 2 anni dopo la somministrazione di CAN-2409
- Il 69% dei pazienti ha mostrato regressione nei tumori non iniettati (effetto abscopale)
- I pazienti con NSCLC non squamoso hanno mostrato risultati superiori con 25,4 mesi di mOS
Il trattamento ha mantenuto un profilo di sicurezza favorevole durante l'intero periodo di follow-up prolungato. La FDA ha concesso la Designazione Fast Track per CAN-2409 in combinazione con il trattamento ICI per pazienti con NSCLC di stadio III/IV resistenti alla terapia di inibitori PD-(L)1 di prima linea.
Candel Therapeutics reportó los datos finales de supervivencia de su ensayo clínico de fase 2a sobre CAN-2409 en pacientes con cáncer de pulmón no microcítico (NSCLC) avanzado que no respondieron al tratamiento con inhibidores de puntos de control inmunitarios (ICI). El estudio mostró resultados notables con una supervivencia global mediana (mOS) de 24.5 meses en la población de pacientes evaluable, superando significativamente los resultados del tratamiento estándar.
Los hallazgos clave incluyen:
- 21.5 meses de mOS en pacientes con enfermedad progresiva a pesar de la terapia ICI, en comparación con 9.8-11.8 meses con quimioterapia estándar de docetaxel
- El 37% de los pacientes sobrevivió más de 2 años después de la administración de CAN-2409
- El 69% de los pacientes mostró regresión en tumores no inyectados (efecto abscopal)
- Los pacientes con NSCLC no escamoso mostraron resultados superiores con 25.4 meses de mOS
El tratamiento mantuvo un perfil de seguridad favorable durante todo el período de seguimiento prolongado. La FDA ha otorgado la Designación de Vía Rápida para CAN-2409 en combinación con tratamiento ICI para pacientes con NSCLC en etapa III/IV resistentes a la terapia de inhibidores PD-(L)1 de primera línea.
Candel Therapeutics는 면역 체크포인트 억제제(ICI) 치료에 반응하지 않은 진행성 비소세포 폐암(NSCLC) 환자를 대상으로 한 CAN-2409의 2a상 임상 시험에서 최종 생존 데이터를 보고했습니다. 이 연구는 평가 가능한 환자 집단에서 중앙 전체 생존 기간(mOS)이 24.5개월로 나타나는 등 주목할 만한 결과를 보여주었으며, 표준 치료 결과를 크게 초과했습니다.
주요 결과는 다음과 같습니다:
- ICI 치료에도 불구하고 진행성 질환을 가진 환자의 mOS가 21.5개월이며, 이는 표준 도세탁셀 화학요법의 9.8-11.8개월에 비해 상당히 개선된 수치입니다.
- 환자의 37%가 CAN-2409 투여 후 2년 이상 생존했습니다.
- 환자의 69%가 비주사 종양에서 퇴행을 보였습니다(부수적 효과).
- 비편평 NSCLC 환자는 25.4개월의 mOS로 우수한 결과를 보였습니다.
치료는 연장된 추적 관찰 기간 동안 우호적인 안전성 프로파일을 유지했습니다. FDA는 1차 PD-(L)1 억제제 치료에 저항하는 III/IV기 NSCLC 환자를 위한 ICI 치료와 함께 CAN-2409에 대해 신속 심사 지정을 부여했습니다.
Candel Therapeutics a rapporté les données finales de survie de son essai clinique de phase 2a sur CAN-2409 chez des patients atteints de cancer du poumon non à petites cellules (NSCLC) avancé qui n'ont pas répondu au traitement par inhibiteurs de points de contrôle immunitaires (ICI). L'étude a montré des résultats remarquables avec une survie globale médiane (mOS) de 24,5 mois dans la population de patients évaluables, dépassant significativement les résultats des soins standards.
Les résultats clés incluent:
- 21,5 mois de mOS chez les patients avec une maladie progressive malgré la thérapie ICI, comparé à 9,8-11,8 mois avec la chimiothérapie standard au docétaxel
- 37 % des patients ont survécu plus de 2 ans après l'administration de CAN-2409
- 69 % des patients ont montré une régression des tumeurs non injectées (effet abscopal)
- Les patients atteints de NSCLC non squameux ont montré des résultats supérieurs avec 25,4 mois de mOS
Le traitement a maintenu un profil de sécurité favorable tout au long de la période de suivi prolongée. La FDA a accordé la désignation Fast Track pour CAN-2409 en combinaison avec le traitement ICI pour les patients atteints de NSCLC de stade III/IV résistant à la thérapie par inhibiteurs PD-(L)1 de première ligne.
Candel Therapeutics hat die endgültigen Überlebensdaten aus seiner Phase-2a-Studie zu CAN-2409 bei fortgeschrittenen nicht-kleinzelligen Lungenkrebspatienten (NSCLC) veröffentlicht, die nicht auf die Behandlung mit Immun-Checkpoint-Inhibitoren (ICI) angesprochen haben. Die Studie zeigte bemerkenswerte Ergebnisse mit einer medianen Gesamtüberlebenszeit (mOS) von 24,5 Monaten in der evaluierbaren Patientengruppe, was die Ergebnisse der Standardbehandlung signifikant übertraf.
Wichtige Ergebnisse sind:
- 21,5 Monate mOS bei Patienten mit progressiver Erkrankung trotz ICI-Therapie, im Vergleich zu 9,8-11,8 Monaten mit der Standardchemotherapie mit Docetaxel
- 37 % der Patienten überlebten mehr als 2 Jahre nach der Verabreichung von CAN-2409
- 69 % der Patienten zeigten eine Regression in nicht injizierten Tumoren (abscopale Wirkung)
- Nicht-squamöse NSCLC-Patienten zeigten mit 25,4 Monaten mOS überlegene Ergebnisse
Die Behandlung wies während des verlängerten Nachbeobachtungszeitraums ein günstiges Sicherheitsprofil auf. Die FDA hat für CAN-2409 in Kombination mit ICI-Behandlungen für Patienten mit resistentem Stadium III/IV NSCLC, die auf die Erstlinientherapie mit PD-(L)1-Inhibitoren nicht ansprechen, die Fast-Track-Designierung erteilt.
- Significantly extended survival: 24.5 months mOS vs 9.8-11.8 months with standard care
- 37% of patients survived beyond 2 years post-treatment
- 69% showed tumor regression in uninjected sites (abscopal effect)
- Superior efficacy in non-squamous NSCLC (25.4 months mOS)
- FDA Fast Track Designation received
- Favorable safety and tolerability profile maintained
- Treatment completion rate shows dropouts: only 46 of 76 enrolled patients completed full treatment
- efficacy in squamous NSCLC patients compared to non-squamous type
- Phase 2a trial design not optimized for intention-to-treat analysis
Insights
The Phase 2a results for CAN-2409 in advanced NSCLC represent a potentially significant breakthrough for patients with options after failing immune checkpoint inhibitor (ICI) therapy. The median overall survival of 21.5 months in patients with progressive disease despite ICI treatment substantially exceeds the 9.8-11.8 months typically seen with docetaxel chemotherapy in this population.
What's particularly striking is the long tail of survival - 37% of patients remaining alive beyond 2 years after treatment suggests durable responses that are rarely seen in advanced NSCLC. The demonstrated abscopal effect (regression of uninjected tumors) in 69% of evaluable patients with multiple lesions indicates robust systemic immune activation rather than just local tumor control.
The differential response based on histology is clinically significant. The 25.4-month median survival in non-squamous NSCLC patients with progressive disease despite ICI treatment represents more than double the expected survival with standard approaches. The biomarker data showing larger changes in T cells, B cells, and dendritic cells in non-squamous patients provides a biological rationale for this difference and enables a precision medicine approach.
The safety profile appears favorable, particularly important when considering quality of life in this patient population where existing chemotherapy options often come with significant toxicities. The FDA's Fast Track Designation reflects the unmet need in this space and should accelerate development timelines.
These Phase 2a results significantly strengthen Candel's clinical and commercial position in the competitive oncology landscape. The substantial survival advantage demonstrated in ICI-refractory NSCLC represents a potential paradigm shift in a large market with effective options for these patients.
The identification of non-squamous histology as a potential predictor of enhanced response provides Candel with a clear path toward a targeted, potentially registrational trial. This precision medicine approach increases the probability of clinical success while addressing a substantial patient population - non-squamous histology represents approximately 70-80% of all NSCLC cases.
The abscopal effect observed in 69% of patients with multiple lesions is particularly valuable, as it suggests CAN-2409 potentially offers systemic disease control from local administration, differentiating it from other localized therapies. This could translate to broader clinical utility and adoption.
The Fast Track Designation already secured from the FDA provides regulatory advantages including more frequent FDA interactions, Rolling Review, and potential Accelerated Approval and Priority Review. This could significantly expedite the path to market compared to standard development timelines.
The favorable safety profile mentioned would position CAN-2409 competitively against chemotherapy options like docetaxel, which are associated with significant toxicities. This could drive both physician adoption and patient preference if approved, potentially leading to rapid market penetration in the second-line setting.
- Experimental treatment with CAN-2409 was associated with a median overall survival (mOS) of 24.5 months in patients with advanced NSCLC who had an inadequate response to ICI treatment, failed several chemotherapy regimens, and presented with multiple negative prognostic factors at enrollment (
90% of the patients had stage IV disease, most patients had low or undetectable PDL-1 expression, >90% were current or former smokers, and most patients had failed multiple lines of chemotherapy) - mOS of 21.5 months was observed in patients with progressive disease at baseline despite ICI therapy (cohort 2), markedly exceeding mOS which has been reported in published literature for this population with standard of care of docetaxel chemotherapy (mOS of 9.8-11.8 months)
- Long tail of survival observed in
37% (15/41) of patients with progressive disease despite ICI treatment at enrollment, who were still alive more than 2 years after CAN-2409 administration at the time of data cutoff (March 3, 2025) - Evidence of a systemic immune response with regression of both injected and uninjected lesions observed in approximately two-thirds of patients with metastatic disease and at least one uninjected tumor (abscopal effect)
- Statistically significant improved overall survival in non-squamous NSCLC compared to squamous NSCLC after experimental treatment with CAN-2409, supported by immunological biomarker data; mOS of 25.4 months in per protocol population of patients with non-squamous NSCLC with progressive disease at baseline despite ICI
- CAN-2409 continued to exhibit a generally favorable safety and tolerability profile throughout the extended follow-up period, with no new safety signals identified
NEEDHAM, Mass., March 26, 2025 (GLOBE NEWSWIRE) -- Candel Therapeutics, Inc. (Candel or the Company) (Nasdaq: CADL), a clinical stage biopharmaceutical company focused on developing multimodal biological immunotherapies to help patients fight cancer, today announced final survival data from a phase 2a clinical trial of CAN-2409 in patients with stage III/IV NSCLC, inadequately responding to ICI treatment. mOS was 24.5 months in 46 evaluable patients receiving 2 courses of CAN-2409 (per protocol population; cohort 1 and 2) and 21.5 months in evaluable patients from cohort 2 (n=41) that presented with progressive disease at baseline, despite ICI treatment. mOS in patients with progressive disease despite ICI treatment, was 9.8-11.8 months in other studies, including those with standard of care of docetaxel chemotherapy, which has a very poor prognosis, did not exceed 12 months in other published studies.(1, 2) This final analysis included extended follow-up data (1 year after the previous data cut) with a median follow up time for the per protocol population of 32.4 months. Data showed a sizable percentage of patients with survival exceeding 24 months, evidence of a long tail of survival, with
Biomarker research showed an enhanced immunological and clinical response after CAN-2409 administration in patients with non-squamous histology compared to squamous histology, and improved mOS was observed in this population (25.4 months in patients with progressive disease despite ICI treatment and non-squamous NSCLC, n=33).
“Treatment options are quite limited for patients with unresectable NSCLC who progress on anti-PD-1 therapy,” said Charu Aggarwal, MD, MPH, Leslye Heisler Professor for Lung Cancer Excellence at the University of Pennsylvania’s Perelman School of Medicine and Principal Investigator of the study. “The survival benefit seen in this study is striking, especially when compared to both the current standard of care treatment of docetaxel chemotherapy and other therapies under investigation for this patient group,” she added.
Data Highlights:
Pre-treatment and mid-treatment dropout rates were comparable to those reported in other clinical trials in similar populations of patients with advanced NSCLC.(1, 3) Three patients were enrolled, but did not receive treatment, 22 patients received only one injection of CAN-2409, 51 patients received at least 2 injections of CAN-2409, but 5 patients did not complete treatment. 46 patients received complete treatment (2 courses of CAN-2409 plus prodrug) and were included in the evaluable, per protocol population. The per protocol population was representative of the overall enrolled population in terms of baseline demographics and prognostic factors.
- Survival data:
- In patients with an inadequate response to ICI treatment (Cohort 1+2, n=46), mOS was 24.5 months.
- In patients with progressive disease, despite ICI treatment (Cohort 2, n=41), mOS was 21.5 months, which is markedly longer than the 9.8–11.8 months of survival reported in published literature in a similar patient population receiving standard of care of docetaxel chemotherapy.1,2
37% of patients exceeding 24 months survival were still alive at the time of the March 3, 2025 data cut.
- Potential precision medicine approach:
- Patients with non-squamous histology predominated amongst the long-term survivors: 14/15 patients with OS > 24 months and 9/9 patients with OS > 30 months had non-squamous NSCLC.
- Patients with non-squamous histology exhibited larger changes in T cells, B cells, and dendritic cells after CAN-2409 administration compared to patients with squamous NSCLC.
- mOS of 25.4 months observed in non-squamous NSCLC patients with progressive disease, despite ICI treatment (n=33).
- Although a phase 2a open-label experimental medicine clinical trial is not designed for an intention to treat (ITT) analysis, we conducted an exploratory ITT analysis and observed mOS of 16.7 months after CAN-2409 administration in non-squamous NSCLC patients with progressive disease despite ICI treatment (n=53). Recent trials have reported a mOS of 9.9–12.3 months in ICI-refractory, non-squamous NSCLC patients receiving standard of care docetaxel chemotherapy.(1,2)
- Systemic anti-tumor response (abscopal effect) and safety profile:
- Decrease in size of uninjected tumors was observed in
69% of patients with multiple lesions (n=35), indicating that local injection may induce a systemic anti-tumor immune response (abscopal effect). - CAN-2409 maintained its generally favorable safety and tolerability profile throughout the extended follow-up period.
- Decrease in size of uninjected tumors was observed in
“These updated survival data confirm and strengthen our previously reported findings, demonstrating that CAN-2409 has the potential to extend survival for patients with advanced NSCLC, who have limited treatment options after failing to respond to, or progressing, despite immune checkpoint inhibitor therapy,” said Paul Peter Tak, MD, PhD, FMedSci, President and Chief Executive Officer of Candel. “CAN-2409 may represent an entirely new approach to solid tumor treatment, with its unique mechanism of action and favorable safety profile to date, enabling potentially meaningful improvements in outcomes beyond current standard of care. These compelling results mark a potentially transformative advance in our fight against this aggressive disease.”
“The extension of survival in patients with non-squamous disease is notable even when compared to data that have been reported for other investigational products, such as antibody-drug conjugates, for this patient population,” said W. Garrett Nichols, MD, CMO of Candel. “CAN-2409, in addition to continued ICI treatment, may prolong survival beyond that offered by docetaxel chemotherapy, and has the potential to be better tolerated.”
Based on these positive findings, the Company will advance its development program for CAN-2409 in NSCLC, including preparation and enabling work for a future, potentially registrational, clinical trial in patients with NSCLC with non-squamous histology. The U.S. Food and Drug Administration (FDA) previously granted Fast Track Designation for CAN-2409 plus valacyclovir in combination with ICI treatment for the treatment of stage III/IV NSCLC in patients who are resistant to first line PD-(L)1 inhibitor therapy and who do not have activating molecular driver mutations or have progressed on directed molecular therapy.
About CAN-2409
CAN-2409, Candel’s most advanced multimodal biological immunotherapy candidate, is an investigational, off-the-shelf, replication-defective adenovirus engineered to deliver the herpes simplex virus thymidine kinase (HSV-tk) gene to a patient’s specific tumor and induce an individualized, systemic immune response against the tumor. HSV-tk is an enzyme that locally converts orally administered valacyclovir into a toxic nucleotide analogue that kills nearby cancer cells. Together, this regimen is designed to induce an individualized and specific CD8+ T cell-mediated response against the injected tumor and uninjected distant metastases for broad anti-tumor activity, based on in-situ vaccination against a variety of tumor antigens. Because of its versatility, CAN-2409 has the potential to treat a broad range of solid tumors. Encouraging monotherapy activity, as well as combination activity with standard of care radiotherapy, surgery, chemotherapy, and immune checkpoint inhibitors, have previously been shown in several preclinical and clinical settings. More than 1,000 patients have been dosed with CAN-2409 with a favorable tolerability profile to date, supporting the potential for combination with other therapeutic strategies.
Candel's clinical development program for CAN-2409 includes completed phase 2a clinical trials in both non-small cell lung cancer (NSCLC) and pancreatic ductal adenocarcinoma (PDAC), as well as a positive pivotal randomized, placebo-controlled phase 3 clinical trial of CAN-2409 in localized, non-metastatic prostate cancer. In December 2024, Candel announced that CAN-2409 achieved its primary endpoint in a phase 3 clinical trial in men with intermediate-to-high-risk, localized prostate cancer, demonstrating statistically significant and clinically meaningful improvement in disease-free survival when added to SoC radiation therapy +/- androgen deprivation therapy. In the Company’s randomized controlled phase 2a clinical trial of CAN-2409 in borderline resectable PDAC, positive survival data showed notable improvement in estimated median overall survival of 31.4 months after experimental treatment with CAN-2409 plus standard of care versus 12.5 months in the control group in patients with PDAC, who received only standard of care. Median survival post-progression was 21.2 months in patients who received CAN-2409 compared to 6.4 months in the control arm. CAN-2409 plus prodrug has been granted Fast Track Designation by the FDA for the treatment of PDAC, stage III/IV NSCLC in patients who are resistant to first line PD-(L)1 inhibitor therapy and who do not have activating molecular driver mutations or have progressed on directed molecular therapy, and localized primary prostate cancer. The FDA has also granted Orphan Drug Designation to CAN-2409 for the treatment of PDAC. Candel’s pivotal phase 3 clinical trial in newly diagnosed, localized prostate cancer was conducted under a Special Protocol Assessment (SPA) agreed with the FDA.
About Candel Therapeutics
Candel is a BLA ready clinical stage biopharmaceutical company focused on developing off-the-shelf multimodal biological immunotherapies that elicit an individualized, systemic anti-tumor immune response to help patients fight cancer. CAN-2409 is the lead product candidate from the adenovirus platform. CAN-3110 is the lead product candidate from the HSV platform and is currently in an ongoing phase 1b clinical trial in recurrent high-grade glioma. In October 2023, the Company announced that Nature published initial results from this ongoing clinical trial: CAN-3110 was well tolerated and the investigators observed nearly two-fold increase in median overall survival compared to historical controls after a single CAN-3110 injection in this therapy-resistant condition.4 Finally, Candel’s enLIGHTEN™ Discovery Platform is a systematic, iterative HSV-based discovery platform leveraging human biology and advanced analytics to create new viral immunotherapies for solid tumors.
For more information about Candel, visit: www.candeltx.com
Forward-Looking Statements
This press release includes certain disclosures that contain “forward-looking statements,” within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, express or implied statements regarding the timing and advancement of current and future development programs; including the timing and availability of additional data and key data readout milestones and presentations; expectations regarding early biological readouts as predictor of clinical response; and expectations regarding the therapeutic benefit of the Company’s programs, including the ability of CAN-2409 to treat a broad range of solid tumors and improve disease-free survival, overall survival, and post-progression survival. The words “may,” “will,” “could,” “would,” “should,” “expect,” “plan,” “anticipate,” “intend,” “believe,” “estimate,” “predict,” “project,” “potential,” “continue,” “target” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Any forward-looking statements in this press release are based on management’s current expectations and beliefs and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this press release, including, without limitation, those risks and uncertainties related to the timing and advancement of development programs; expectations regarding the therapeutic benefit of the Company’s programs; that final data from the Company’s pre-clinical studies and completed clinical trials may differ materially from reported interim data from ongoing studies and trials; the Company’s ability to efficiently discover and develop product candidates; the Company’s ability to obtain and maintain regulatory approval of product candidates; the Company’s ability to maintain its intellectual property; the implementation of the Company’s business model, including strategic plans for the Company’s business and product candidates; and other risks identified in the Company’s filings with the U.S. Securities and Exchange Commission (SEC) including the Company’s most recent Annual Report on Form 10-K filed with the SEC and any subsequent filings with the SEC. The Company cautions you not to place undue reliance on any forward-looking statements, which speak only as of the date they are made. The Company disclaims any obligation to publicly update or revise any such statements to reflect any change in expectations or in events, conditions, or circumstances on which any such statements may be based, or that may affect the likelihood that actual results will differ from those set forth in the forward-looking statements. Any forward-looking statements contained in this press release represent the Company’s views only as of the date hereof and should not be relied upon as representing its views as of any subsequent date.
Investor Contact:
Theodore Jenkins
VP, Investor Relations and Business Development
Candel Therapeutics, Inc.
tjenkins@candeltx.com
Media Contact:
Ben Shannon
ICR Healthcare
CandelPR@icrhealthcare.com
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1 Paz-Ares LG et al. J Clin Oncol 2024;42:2860-2872
2 Ahn MJ et al. J Clin Onc 2024;43:260-272
3 Reckamp,KL et al. J Clin Oncol. 2022; 40 :2295-2306
4 Ling AL, et al. Nature. 2023;623(7985):157-166.
FAQ
What survival rates did CAN-2409 achieve in the Phase 2a NSCLC trial (CADL)?
How does CAN-2409's effectiveness compare to standard treatment in NSCLC patients?
What is the abscopal effect observed in Candel's (CADL) NSCLC trial?
Which NSCLC patient group showed the best response to CAN-2409 treatment?
What regulatory status has CAN-2409 received from the FDA for NSCLC treatment?
