VPM1002 / Max Planck Institute, SAKK, Serum Institute of India - LARVOL DELTA

Intravesical recombinant BCG followed by perioperative chemo-immunotherapy (chemo-IO) for patients with muscle-invasive bladder cancer (MIBC): Interim analysis of SAKK 06/19 study (ESMO 2025) - P2 | "We previously investigated a recombinant BCG vaccine (rBCG, VPM1002BC) demonstrating good safety and efficacy (SAKK 06/14)...Atezolizumab (Atezo) 1200 mg is administered on day 1 and then 4 times every 3 weeks (q3w). Cisplatin and gemcitabine start on day 22 and are given for 4 cycles q3w followed by radical cystectomy (RC)...Conclusions The combination of intravesical rBCG with perioperative chemo-IO was feasible and well-tolerated without unexpected toxicities. The interim analysis met predefined efficacy and safety criteria and the trial continues enrollment into stage 2."

Clinical • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

Intravesical recombinant BCG followed by perioperative chemo-immunotherapy for patients with muscle-invasive bladder cancer (MIBC): A multicenter, single arm phase 2 trial (SAKK 06/19). (ASCO-GU 2024) - P2 | "Recently, a novel recombinant BCG vaccine (VPM1002BC) has been developed and a clinical study in BCG-refractory NMIBC (SAKK 06/14, Eur Urol Oncol...Atezolizumab (atezo) 1200mg is given on day 1 and then every 3 weeks (q3w) for four times. Chemotherapy with cisplatin (70mg/m2 day 1) and gemcitabine (1000mg/m2 day 1 & 8) q3w is started on day 22 and given for four cycles followed by radical cystectomy and lymphadenctomy...Accrual to the study is currently ongoing (NCT04630730). Clinical trial information: NCT04630730."

Clinical • P2 data • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

Intravesical recombinant BCG combined with chemo-immunotherapy (chemo-IO) as perioperative therapy for patients with muscle-invasive bladder cancer (MIBC): Primary analysis of SAKK 06/19. (ASCO 2026) - P2 | "The recombinant BCG vaccine VPM1002BC (rBCG) is associated with enhanced immunogenicity and an improved safety profile...Atezolizumab (Atezo) 1200 mg was administered on day 1 and then x4 every 3 weeks (q3w). Cisplatin and gemcitabine started on day 22 and were given for 4 cycles q3w followed by RC...98% received 4 doses of Atezo and 95% had 4 cycles of platinum (20% switched to carboplatin)... This is the first trial to combine intravesical rBCG with chemo-IO in MIBC. The combination was feasible and safe without unexpected toxicities. The centrally assessed pCR rate of 65% and PaR of 80% are among the highest reported in an unselected MIBC population."

Clinical • Bladder Cancer • Genito-urinary Cancer • Immune Modulation • Immunology • Oncology • Solid Tumor

Comparison of VPM1002 with BCG in the prevention of tuberculosis in newborn infants: a multicentre, double-blind, randomised, phase 3, non-inferiority trial. (PubMed, Lancet Infect Dis) - P3 | "VPM1002 did not show non-inferiority to BCG on the primary endpoint of QFT conversion. Because fewer infections occurred than expected (334 of 632 planned events, despite extending the duration to 48 months), the trial did not have sufficient statistical certainty to definitively compare the two vaccines. Moreover, discordance between the QFT surrogate and confirmed tuberculosis endpoints, approximately 33·0% higher household tuberculosis exposure in the VPM1002 group, and violation of the proportional hazards assumption when tuberculosis exposure was included as a covariate (that is, the effect of tuberculosis exposure on QFT conversion was not constant over time, precluding reliable HR estimation without penalised modelling) collectively add to this uncertainty. Both vaccines showed similar adverse event profiles. These findings highlight challenges in using IGRA-defined infection endpoints in infant vaccine trials."

Head-to-Head • Journal • P3 data • Human Immunodeficiency Virus • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis • IFNG

Safety and Immunogenicity of VPM1002 Vaccination or BCG Revaccination Against TB in Pre-Adolescents Living With and Without HIV in South Africa (clinicaltrials.gov) - P1/2 | N=0 | Withdrawn | Sponsor: International Maternal Pediatric Adolescent AIDS Clinical Trials Group | Trial completion date: Jul 2027 ➔ Dec 2026 | Trial primary completion date: Jul 2027 ➔ Dec 2026

Trial completion date • Trial primary completion date • Human Immunodeficiency Virus • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis • CD4

Advances in development of tuberculosis vaccines and preventive drug therapies: current pipeline, evidence, and access. (PubMed, Lancet Microbe) - "Platforms include live-attenuated mycobacterial vaccines (eg, MTBVAC), recombinant BCG-derived approaches (eg, VPM1002), protein-adjuvant subunit vaccines (eg, M72/AS01E), viral-vectored candidates (eg, AdHu5Ag85A, ChAdOx1.85A, and TB/FLU-04L), and inactivated whole-cell strategies (eg, DAR-901, RUTI, and Immuvac [MIP])...For contacts of multidrug-resistant or rifampicin-resistant tuberculosis, randomised trials and pooled analyses support 6 months of daily levofloxacin to reduce incident multidrug-resistant tuberculosis. Bedaquiline-containing preventive regimens and shorter fluoroquinolone-based combinations are under clinical evaluation, but definitive phase 3 efficacy data are not yet available. The expansion of the vaccine pipeline alongside improved short-course preventive regimens offers a credible opportunity to accelerate tuberculosis incidence decline, although translation into population-level impact will depend on shown efficacy, sustained financing, reliable..."

Journal • Review • Human Immunodeficiency Virus • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Immunotherapy for tuberculosis: current landscape, mechanistic insights, and translational perspectives. (PubMed, Front Immunol) - "This review integrates recent advances across the immunotherapy landscape, including next-generation vaccines (M72/AS01E, MTBVAC, VPM1002, BNT164 mRNA candidates), host-directed therapies (HDTs) targeting autophagy, metabolic and inflammatory pathways, cytokine-based and antimicrobial peptide strategies, and adoptive cell therapies. Key translational challenges-the absence of reliable correlates of protection, the demand for precision immunomodulation in comorbid populations (HIV, diabetes), and chronic underfunding of TB research-are discussed alongside emerging opportunities offered by mRNA platforms, repurposed drugs, and multi-omics-guided patient stratification. Collectively, immunotherapy is evolving from an adjunctive concept into a strategic pillar of TB control, with the potential to shorten treatment, prevent relapse, and address drug-resistant disease."

Journal • Review • Diabetes • Human Immunodeficiency Virus • Immunology • Infectious Disease • Metabolic Disorders • Pulmonary Disease • Respiratory Diseases • Tuberculosis • PD-1 • PD-L1

Addition of Intravesical Recombinant BCG to Perioperative Chemo-Immunotherapy in Muscle-Invasive Bladder Cancer: Primary Analysis of the Single-Arm Phase 2 Trial SAKK 06/19. (PubMed, J Clin Oncol) - "This is the first trial combining intravesical rBCG with chemo-immunotherapy in MIBC, demonstrating high pCR and PaR rates that warrant further investigation in prospective randomized trials."

Journal • P2 data • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

…Primary analysis of SAKK 06/19, presented at the 2026 ASCO Annual Meeting (Targeted Oncology) - " Intravesical rBCG priming plus systemic chemoimmunotherapy achieved ypT0N0 in 68% and ≤ypT1N0 in 83% among cystectomy patients, surpassing the Simon minimax efficacy threshold. Treatment delivery was high, but 15% did not undergo cystectomy, predominantly due to refusal, underscoring feasibility challenges with complex multidisciplinary perioperative regimens. Clinical CR by multimodal restaging showed strong correlation with pCR (PPV 92%, NPV 69%), supporting its potential utility as a response-enrichment or de-escalation tool."

P2 data • Bladder Cancer

Study to Assess VPM1002 in Reducing Healthcare Professionals' Absenteeism in COVID-19 Pandemic (clinicaltrials.gov) - P3 | N=59 | Completed | Sponsor: Serum Life Science Europe GmbH | Active, not recruiting ➔ Completed

Trial completion • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Correction: Efficacy and safety of VPM1002 and Immuvac in preventing tuberculosis: phase 3 randomised clinical trial (PreVenTB trial). (PubMed, BMJ) - No abstract available

Journal • P3 data • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Efficacy and safety of VPM1002 and Immuvac in preventing tuberculosis: phase 3 randomised clinical trial (PreVenTB trial). (PubMed, BMJ) - "Both vaccines were safe but did not show any efficacy against all forms of microbiologically confirmed TB or pulmonary TB. VPM1002 showed considerable efficacy against extrapulmonary TB. Both vaccines showed efficacy against extrapulmonary TB in participants who had a positive tuberculin skin test."

Clinical • Journal • P3 data • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis • CD4

ResQ133A-NMIBC: A phase 1/2 clinical trial of intravesical recombinant mycobacterium bacillus Calmette-Guerin (rBCG) in participants living with non-muscle invasive bladder cancer eligible to receive conventional BCG. (ASCO-GU 2026) - P1/2 | "As reported in the SAKK06/14 trial, rBCG VPM1002BC was found to be efficacious and safe in NMIBC recurrence after conventional BCG therapy [Rentsch 2022 ]...Response assessments will occur every 12 weeks through week 52. As of October 21, 2025, the study is open and awaiting the enrollment of its first participant."

Clinical • P1/2 data • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

Status of Tuberculosis Vaccines Development in Clinical Trials (PubMed, Jugan Geongang Gwa Jilbyeong) - "The recombinant protein-based M72/AS01E vaccine has been mentioned as a potential vaccine, and is currently recruiting subjects for a Phase 3 clinical trial. In addition, recombinant protein-based GemTBvac and whole cell-based MIP, MTBVAC, and VPM1002 are in Phase 3 clinical trials. While several platform-based TB vaccine candidates are in clinical trials; however, the antigens contained in these candidates are often redundant and limited. To diversify the TB vaccine clinical pipeline, it is necessary to continue research to identify new antigens, the development of preclinical animal models for efficacy evaluation, and the identification of valid endpoints through the analysis of clinical trial results are necessary."

Journal • Review • Infectious Disease • Novel Coronavirus Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Overcoming Treatment Challenges in HIV-Associated Mycobacterial Diseases: New Therapeutic Frontiers. (PubMed, Int J Mol Sci) - "Beyond established regimens, we highlight host-directed strategies such as metformin, glutathione augmentation, mTOR modulation, and vitamin D; immunotherapies including interferon-γ, GM-CSF, and IL-7; and therapeutic vaccines (M72/AS01E, MTBVAC, VPM1002) as promising adjuncts. Distinct from guideline-focused overviews, this review emphasizes non-tuberculous mycobacterial disease (NTM, including MAC) and leprosy in PLWH and synthesizes host-directed and adjunctive strategies with their translational prospects, including ART compatibility and IRIS. By integrating TB, NTM, and leprosy across the HIV care continuum, we highlight opportunities not treated in detail elsewhere-particularly HDT-enabled approaches and implementation considerations in PLWH."

Journal • Review • Human Immunodeficiency Virus • Infectious Disease • Nontuberculous Mycobacterial Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis • CSF2 • IFNG • IL7

ResQ132Ex-NMIBC: EXPANDED ACCESS OF RECOMBINANT MYCOBACTERIUM BACILLUS CALMETTE-GUERIN IN NON-MUSCLE INVASIVE BLADDER CANCER (SUO 2025) - P, P1/2 | "In the SAKK06/14 trial, rBCG VPM1002BC was demonstrated to be efficacious and safe in NMIBC recurrence after conventional BCG therapy [Rentch 2022]...As of August 5, 2025, over 150 patients have received expanded access to rBCG at 25+ Urology locations in the United States. "

Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urology

Adult TB vaccine: Possible novel tool to end TB (MTS 2025) - "We will discuss the immunopathogenesis of TB and how it informs vaccine development, highlighting key vaccine candidates such as M72/AS01E, VPM1002, and BCG revaccination strategies. Furthermore, the lecture will address how adult TB vaccination could synergize with existing TB control strategies, including latent TB treatment, diagnostics, and public health interventions. Special focus will be given to implementation considerations, including population targeting, delivery logistics, and cost-effectiveness in low- and middle-income countries."

Clinical • Infectious Disease • Respiratory Diseases • Tuberculosis

Sex Differences in Vaccine-Induced Immunity and Protection Against Mycobacterium tuberculosis. (PubMed, J Infect Dis) - "In this study, we vaccinated male and female C57BL/6 mice with BCG and 2 recombinant derivatives, VPM1002 and BCGΔBCG1419c, and assessed their protection against Mycobacterium tuberculosis (Mtb) HN878...Vaccination of males with BCGΔBCG1419c, but not BCG, enhanced CD8 T-cell and B-cell recall responses in vaccine-draining lymph nodes, and reduced lung inflammation after Mtb challenge. These findings underscore the impact of sex differences on vaccine efficacy and suggest that future research should consider sex as a biological variable to optimize TB vaccination strategies."

Journal • Infectious Disease • Inflammation • Pneumonia • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Study to Check the Efficacy and Safety of Recombinant BCG Vaccine in Prevention of TB Recurrence (clinicaltrials.gov) - P2/3 | N=2000 | Completed | Sponsor: Serum Institute of India Pvt. Ltd. | Active, not recruiting ➔ Completed

Trial completion • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Evaluation of Efficacy and Safety of VPM1002 in Comparison to BCG in Prevention of Tb Infection in Infants (clinicaltrials.gov) - P3 | N=6940 | Completed | Sponsor: Serum Institute of India Pvt. Ltd. | Active, not recruiting ➔ Completed | Trial completion date: Dec 2025 ➔ Oct 2024 | Trial primary completion date: Dec 2025 ➔ Oct 2024

Trial completion • Trial completion date • Trial primary completion date • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

PreVenTB trial: protocol for evaluation of efficacy and safety of two vaccines VPM1002 and Immuvac (Mw) in preventing tuberculosis (TB) in healthy household contacts of newly diagnosed sputum smear-positive pulmonary TB patients: phase III, randomised, double-blind, three-arm placebo-controlled trial. (PubMed, BMJ Open) - "The results of this clinical trial will be presented at scientific conferences and disseminated through publications in peer-reviewed journals, conference presentations and shared with Ministry of Health and Family Welfare, policy-makers and other stakeholders. CTRI/2019/01/017026."

Clinical • Clinical protocol • Journal • P3 data • Human Immunodeficiency Virus • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis • CD4 • CD8

Safety and Immunogenicity of VPM1002 Vaccination or BCG Revaccination Against TB in Pre-Adolescents Living With and Without HIV in South Africa (clinicaltrials.gov) - P1/2 | N=0 | Withdrawn | Sponsor: International Maternal Pediatric Adolescent AIDS Clinical Trials Group | N=480 ➔ 0 | Not yet recruiting ➔ Withdrawn

Enrollment change • Trial withdrawal • Human Immunodeficiency Virus • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis • CD4 • CD8

Evaluation of Efficacy and Safety of VPM1002 in Comparison to BCG in Prevention of Tb Infection in Infants (clinicaltrials.gov) - P3 | N=6940 | Active, not recruiting | Sponsor: Serum Institute of India Pvt. Ltd. | Trial primary completion date: Aug 2023 ➔ Dec 2025

Trial primary completion date • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Study to Check the Efficacy and Safety of Recombinant BCG Vaccine in Prevention of TB Recurrence (clinicaltrials.gov) - P2/3 | N=2000 | Active, not recruiting | Sponsor: Serum Institute of India Pvt. Ltd. | Trial completion date: Feb 2024 ➔ Jul 2024

Trial completion date • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Safety and Immunogenicity of VPM1002 Vaccination or BCG Revaccination Against TB in Pre-Adolescents Living With and Without HIV in South Africa (clinicaltrials.gov) - P1/2 | N=480 | Not yet recruiting | Sponsor: International Maternal Pediatric Adolescent AIDS Clinical Trials Group | Trial completion date: Oct 2026 ➔ Jul 2027 | Trial primary completion date: Oct 2026 ➔ Jul 2027

Trial completion date • Trial primary completion date • Human Immunodeficiency Virus • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis • CD4 • CD8