zinlirvimab (GS-2872) / National Institute of Allergy and Infectious Diseases, Rockefeller University, Gilead - LARVOL DELTA

Evaluation of Safety, Immunogenicity and Efficacy of a Triple Immune Regimen in Adults Initiated on ART During Acute HIV-1 (clinicaltrials.gov) - P1/2 | N=45 | Recruiting | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Trial completion date: Apr 2026 ➔ Aug 2029 | Trial primary completion date: Apr 2026 ➔ Apr 2028

Trial completion date • Trial primary completion date • Human Immunodeficiency Virus • Infectious Disease • CD4

Study to Evaluate the Safety and Efficacy of Teropavimab and Zinlirvimab in Combination With Lenacapavir in Virologically Suppressed Adults With HIV-1 Infection (clinicaltrials.gov) - P1 | N=32 | Completed | Sponsor: Gilead Sciences | Phase classification: P1b ➔ P1

Phase classification • Human Immunodeficiency Virus • Infectious Disease • CD4

ACACIA: Antiretrovirals Combined With Antibodies for HIV-1 Cure In Africa (clinicaltrials.gov) - P2 | N=135 | Recruiting | Sponsor: Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections | Not yet recruiting ➔ Recruiting

Enrollment open • Human Immunodeficiency Virus • Infectious Disease

ACACIA: Antiretrovirals Combined with Antibodies for HIV-1 Cure in Africa (clinicaltrials.gov) - P2 | N=135 | Not yet recruiting | Sponsor: Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections | Initiation date: Oct 2024 ➔ Jan 2025

Trial initiation date • Human Immunodeficiency Virus • Infectious Disease

Efficacy and safety analysis of lenacapavir with broadly neutralising antibodies, teropavimab and zinlirvimab, in people with HIV-1 highly sensitive to one or both broadly neutralising antibodies (HIV-Glasgow 2024) - P1b | "Conclusions : All participants who received LEN, TAB and high-dose ZAB maintained viral suppression with no difference in safety or tolerability between dose groups. These early phase results suggest that high treatment efficacy for the long-acting regimen of LEN, TAB and high-dose ZAB can be achieved when at least one antibody is highly active in people with HIV highly susceptible to one or both bNAbs."

Clinical • Human Immunodeficiency Virus • Infectious Disease • CD4

3BNC117-LS and 10-1074-LS Plus N-803 (bNAb+N-803) (clinicaltrials.gov) - P1 | N=28 | Active, not recruiting | Sponsor: Rockefeller University | Recruiting ➔ Active, not recruiting

Enrollment closed • Human Immunodeficiency Virus • Infectious Disease • CD4

Susceptibility to lenacapavir, fostemsavir and broadly neutralizing antibodies in French primary HIV-1 infected patients in 2020-2023. (PubMed, J Med Virol) - "Predictive sensitivity was evaluated for maraviroc and broadly neutralizing antibodies (bNAbs) (zinlirvimab and teropavimab). The genotypic profile was associated with a predictive positive value (PPV) > 83% of susceptibility to both teropavimab and zinlirvimab for 23 viruses (31%), while 22 (29%) had a PPV between 62% and 75%, suggesting reduced susceptibility to both bNAbs as soon as primary infection. The surveillance of TDR evidenced at the time of PHI is important with regard to new strategies for HIV patients with virological failure and global implementation of PrEP using NRTI, INI such as recently approved injectable cabotegravir, and future long-acting drugs such as lenacapavir and bNAbs."

Journal • Human Immunodeficiency Virus • Infectious Disease • CXCR4

Susceptibility Screening of HIV-1 Viruses to Broadly Neutralizing Antibodies, Teropavimab and Zinlirvimab, in People with HIV-1 Suppressed by Antiretroviral Therapy. (PubMed, J Acquir Immune Defic Syndr) - "bNAb susceptibility was correlated among all three in-vitro assays used to determine teropavimab and zinlirvimab susceptibility in virally suppressed PWH. These findings may help refine PWH selection criteria for eligibility for future studies."

Journal • Human Immunodeficiency Virus • Infectious Disease

Potent and broadly neutralizing HIV-1 antibodies with improved pharmacokinetics achieved by negative supercharging (AIDS 2024) - "While confirmation is needed regarding whether the enhanced potency observed in in vitro pseudovirus assays translates to improved protection in non-human primates, the conservation of the CH1 and CL domains in IgG1 suggests that these substitutions in the CH1 and CL, along with the addition of acidic tails, have the potential to enhance the PK and potency of various therapeutic antibodies."

Late-breaking abstract • PK/PD data • Human Immunodeficiency Virus • Infectious Disease

Resistance analyses during treatment of lenacapavir with broadly neutralizing antibodies in people with HIV (AIDS 2024) - "BACKGROUND: Combination of lenacapavir (LEN) with broadly neutralizing antibodies (bNAbs) teropavimab (TAB; 30 mg/kg), and zinlirvimab (ZAB; either 10 or 30 mg/kg) was investigated in a phase 1b randomized clinical study in virally suppressed people with HIV. High rates of virologic suppression were maintained during treatment with LEN and bNAbs, including among participants susceptible to only one bNAb. Development of low-copy number genotyping allowed geno- and phenotypic resistance analyses in three participants with VR, with emergent LEN resistance only detected for one participant. All three participants with VR received 10 mg/kg of ZAB, suggesting a higher dose of ZAB may decrease risk of VR."

Human Immunodeficiency Virus • Infectious Disease

Comparison of HIV-specific broadly neutralising antibodies resistance prediction using plasma RNA, blood, and gut tissue HIV proviral sequences (AIDS 2024) - P2 | "Screening potential participants for bNAb resistance is common in clinical trials, however the optimal strategy to determine viral sensitivity, and whether plasma virus or proviral samples can be used is yet to be defined. We analysed samples (PBMC-derived HIV DNA sequences and rebound plasma envelope sequences (n=17), paired[SF1] baseline rectal biopsies (n=4)) from participants in the unblinded placebo arm of the RIO trial (RCT of 3BNC117-LS and 10-1074-LS in primary HIV infection; NCT04319367). HIV-1 envelope sequence-based bNAb resistance screening using proviral DNA from PBMC was consistent with predicted viral sensitivities from plasma virus at time of rebound. This has implications for sample choice for bNAb screening. The study findings are limited by small numbers, and to participants with proviral sequences predicted as sensitive at baseline."

Human Immunodeficiency Virus • Infectious Disease

A Study of GS-5423 and GS-2872 in Combination With Capsid Inhibitor Lenacapavir in Virologically Suppressed Adults With HIV-1 Infection (clinicaltrials.gov) - P2 | N=83 | Active, not recruiting | Sponsor: Gilead Sciences | Trial primary completion date: Mar 2025 ➔ Jul 2024

Combination therapy • Trial primary completion date • Human Immunodeficiency Virus • Infectious Disease • CD4

Impact of LS Mutation on Pharmacokinetics of Preventive HIV Broadly Neutralizing Monoclonal Antibodies: A Cross-Protocol Analysis of 16 Clinical Trials in People without HIV. (PubMed, Pharmaceutics) - "To characterize the LS mutation for monoclonal antibodies targeting HIV, we compared pharmacokinetic parameters between parental versus LS variants for five pairs of anti-HIV immunoglobin G1 monoclonal antibodies (VRC01/LS/VRC07-523LS, 3BNC117/LS, PGDM1400/LS PGT121/LS, 10-1074/LS), analyzing data from 16 clinical trials of 583 participants without HIV. Results suggest a favorable pharmacokinetic profile of LS variants regardless of HIV epitope specificity. Insights support lower dosages and/or less frequent dosing of LS variants to achieve similar levels of antibody exposure in future clinical applications."

Journal • PK/PD data • Human Immunodeficiency Virus • Infectious Disease

ACACIA: Antiretrovirals Combined With Antibodies for HIV-1 Cure In Africa (clinicaltrials.gov) - P2 | N=135 | Not yet recruiting | Sponsor: AIDS Clinical Trials Group | Trial primary completion date: Jan 2026 ➔ Feb 2029

Trial primary completion date • Human Immunodeficiency Virus • Infectious Disease

RIO: A Randomised Placebo Controlled Trial of ART Plus Dual Long-acting HIV-specific Broadly Neutralising Antibodies (bNAbs). (clinicaltrials.gov) - P2 | N=72 | Recruiting | Sponsor: Imperial College London | Trial completion date: Mar 2025 ➔ Jul 2027 | Trial primary completion date: Dec 2023 ➔ Jul 2027

Trial completion date • Trial primary completion date • Human Immunodeficiency Virus • Infectious Disease • CD4 • CD8

RHIVIERA-02: Phase II Trial of ART + Dual bNAbs vs. ART + Placebo During Primary HIV-1 Infection-impact on Post-ART Control (clinicaltrials.gov) - P2 | N=69 | Recruiting | Sponsor: ANRS, Emerging Infectious Diseases | Not yet recruiting ➔ Recruiting

Enrollment open • Human Immunodeficiency Virus • Infectious Disease

Evaluation of Safety, Immunogenicity and Efficacy of a Triple Immune Regimen in Adults Initiated on ART During Acute HIV-1 (clinicaltrials.gov) - P1/2 | N=45 | Recruiting | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Not yet recruiting ➔ Recruiting

Enrollment open • Human Immunodeficiency Virus • Infectious Disease • CD4

Teropavimab and Zinlirvimab Sensitivity in People Living With MDR HIV-1: PRESTIGIO Registry Data (CROI 2024) - P | "A significant number of the analyzed 4DR-PWH were found to have virus susceptible to TAB and ZAB. These data provide proof-of-concept that selected multidrug-resistant PWH may be candidates for future trials investigating bNAbs-containing regimens to achieve or maintain virologic suppression."

Human Immunodeficiency Virus • Infectious Disease • CD4

Lenacapavir Plus bNAbs for People With HIV and Sensitivity to Either Teropavimab or Zinlirvimab (CROI 2024) - P1b | "The long-acting combination of LEN+TAB+ZAB was well tolerated, with a favorable safety profile. All participants in the higher ZAB dose group maintained VS for 6 months, which suggests that more inclusive sensitivity criteria may be appropriate for treatment studies of LEN+TAB+ZAB when higher bNAb levels are maintained."

Hepatitis B • Hepatology • Human Immunodeficiency Virus • Infectious Disease • Inflammation • Novel Coronavirus Disease • CD4

Safety of teropavimab and zinlirvimab with lenacapavir once every 6 months for HIV treatment: a phase 1b, randomised, proof-of-concept study. (PubMed, Lancet HIV) - P1b | "Lenacapavir with teropavimab and zinlirvimab 10 mg/kg or 30 mg/kg was generally well tolerated with no serious adverse events. HIV-1 suppression for at least 26 weeks is feasible with this regimen at either zinlirvimab dose in selected people with HIV-1."

Journal • P1 data • Dermatology • Human Immunodeficiency Virus • Infectious Disease • CD4

ACACIA: Antiretrovirals Combined With Antibodies for HIV-1 Cure In Africa (clinicaltrials.gov) - P2 | N=135 | Not yet recruiting | Sponsor: AIDS Clinical Trials Group

New P2 trial • Human Immunodeficiency Virus • Infectious Disease

A Study of GS-5423 and GS-2872 in Combination With Capsid Inhibitor Lenacapavir in Virologically Suppressed Adults With HIV-1 Infection (clinicaltrials.gov) - P2 | N=83 | Active, not recruiting | Sponsor: Gilead Sciences | Recruiting ➔ Active, not recruiting

Combination therapy • Enrollment closed • Human Immunodeficiency Virus • Infectious Disease • CD4

RHIVIERA-02: Phase II Trial of ART + Dual bNAbs vs. ART + Placebo During Primary HIV-1 Infection-impact on Post-ART Control (clinicaltrials.gov) - P2 | N=69 | Not yet recruiting | Sponsor: ANRS, Emerging Infectious Diseases

Trial completion date • Trial primary completion date • Human Immunodeficiency Virus • Infectious Disease

Study to Evaluate the Safety and Efficacy of Teropavimab and Zinlirvimab in Combination With Lenacapavir (GS-6207) in Virologically Suppressed Adults With HIV-1 Infection (clinicaltrials.gov) - P1b | N=32 | Completed | Sponsor: Gilead Sciences | Active, not recruiting ➔ Completed

Combination therapy • Trial completion • Human Immunodeficiency Virus • Infectious Disease • CD4

3BNC117-LS and 10-1074-LS Plus N-803 (bNAb+N-803) (clinicaltrials.gov) - P1 | N=36 | Recruiting | Sponsor: Rockefeller University | Trial primary completion date: Dec 2024 ➔ Dec 2025

Trial primary completion date • Human Immunodeficiency Virus • Infectious Disease • CD4