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10-1074
Other Names
zinlirvimab, GS-2872, 10-1074-LS and 10-1074-LS-J (long-acting forms of 10-1074)
Drug Class
Broadly Neutralizing Antibodies
Organization
Rockefeller University; Gilead Sciences
Phase of Development

10-1074 is in Phase 2 development as a broadly neutralizing antibody for HIV treatment. (10-1074 is also being developed for HIV prevention.)

(Compound details obtained from Treatment Action Group website,1 Treatment Action Group Pipeline Report 2022,2 and Gilead Sciences press release3)

 
What is 10-1074?What is 10-1074?

What is 10-1074?

10-1074 is an investigational drug that is being studied as a possible strategy to treat people living with HIV. 10-1074 belongs to a group of drugs called broadly neutralizing antibodies (bNAbs).1

To learn how investigational drugs are tested during clinical trials, read the HIVinfo What is an Investigational HIV Drug? and HIV and AIDS Clinical Trials fact sheets.

How do broadly neutralizing antibodies work?How do broadly neutralizing antibodies work?

How do broadly neutralizing antibodies work?

Antibodies are proteins that the immune system makes to fight infection. A person with HIV produces specific antibodies against HIV. However, most of these antibodies do not stop HIV from multiplying in the body.4,5

Some people with HIV naturally produce rare types of HIV antibodies called broadly neutralizing antibodies (bNAbs). bNAbs are powerful antibodies that can work against different HIV strains. bNAbs can block HIV from entering healthy cells and activate other immune cells to help destroy infected cells.4,6,7

Researchers are investigating whether giving bNAbs to people with HIV can help them maintain undetectable levels of HIV without the need for daily antiretroviral therapy. Additionally, some bNAbs are being studied because they may be able to reduce the size of the latent HIV reservoir.6,8

Researchers are also trying to find out if 10-1074 can prevent HIV infection in people who do not have the virus.2 This record focuses on the study of 10-1074 as a treatment for HIV.

Select clinical trials of 10-1074Select clinical trials of 10-1074

Select clinical trials of 10-1074

Study Names: Tatelo Study; NCT03707977

Phase: 1/2
Status: This study has been completed.
Location: Botswana
Purpose: The purpose of this study was to evaluate the efficacy of 10-1074 and another investigational bNAb called VRC01LS in maintaining viral suppression in a group of children who had received early antiretroviral therapy (ART).9
Selected Study Results: Results presented at CROI 2022 showed that treatment with both 10-1074 and VRC01LS (given either individually or in combination) was generally safe and effective. Participants with a longer time on ART and bNAb overlap were more likely to succeed along with participants who enrolled earlier in the study and had favorable pre-intervention clinical and reservoir characteristics. There were no infusion reactions or severe side effects related to bNAb treatment.10

Additional Published Material:

Study Names: HIVACAR; NCT03619278

Phase: 1/2a
Status: See the ClinicalTrials.gov record for this study’s status.
Location: Not available
Purpose: The purpose of this study is to evaluate the safety and efficacy of combinations of therapeutic HIV vaccines with 10-1074 and the latency-reversing agent romidepsin in controlling viral load levels during an analytical treatment interruption of ART.11

Study Name: NCT04357821

Phase: 1/2
Status: This study is ongoing, but not recruiting participants.
Location: United States
Purpose: The purpose of this study is to evaluate whether a combination regimen consisting of therapeutic HIV vaccines, the bNAbs VRC07-523LS plus 10-1074, and lefitolimod can control viral load levels during an analytical treatment interruption of ART.12
Selected Study Results: Results presented at CROI 2023 indicated that most of the participants (seven out of 10) who received combination therapy had at least partial virologic control after an analytical treatment interruption of ART.13

Study Names: TITAN; NCT03837756

Phase: 2a
Status: This study is ongoing, but not recruiting participants.
Location: United States, Australia, Denmark, and Norway
Purpose: The purpose of this study was to evaluate the safety and efficacy of lefitolimod plus the bNAbs 3BNC117 and 10-1074 in delaying the time to viral rebound during an analytical treatment interruption of ART.14
Selected Study Results: Results presented at CROI 2023 showed that the groups receiving dual bNAb treatment had a significant delay in the time to viral rebound during an analytical treatment interruption of ART, as compared to groups receiving placebos only or lefitolimod plus placebo. The addition of lefitolimod to dual bNAb treatment did not confer any additional effect on viral control compared to dual bNAb treatment alone.15

Study Names: RIO; NCT04319367

Phase: 2
Status: This study is currently recruiting participants.
Location: United Kingdom
Study Purpose: The purpose of this study is to determine whether the combination of two long-acting bNAbs, 3BNC117-LS and 10-1074-LS, can prevent viral rebound after an analytical treatment interruption of ART.16,17

For more details on the studies listed above, see the Health Professional version of this drug summary.

Additional studies evaluating 10-1074 for HIV treatment have been completed or are being conducted, including the following early-phase trials:

  • NCT03526848: A Phase 1 study that evaluated whether 3BNC117 and 10-1074 could control viral load levels in adults with HIV during an analytical treatment interruption of ART. This study has been completed and results are available.18
  • NCT04250636: A Phase 1 study that evaluated the safety, pharmacokinetics, and antiviral activity of single infusions of both 3BNC117-LS and 10-1074-LS in adults with HIV who were off ART. This study has been completed and results are available.19
  • NCT04811040: A Phase 1b study evaluating the safety and efficacy of 3BNC117-LS (also known as GS-5423) and 10-1074-LS (also known as GS-2872) in combination with the capsid inhibitor lenacapavir in controlling viral load levels in adults with viral suppression. This study is ongoing, but not recruiting participants. Results were presented at CROI 2023.20
  • BEAT-2 (NCT03588715): A Phase 1 study that evaluated whether the immune modulator peginterferon alfa-2b plus 3BNC117 and 10-1074 could control viral rebound and reduce the latent HIV reservoir in adults with HIV during an analytical treatment interruption of ART. This study has been completed and main outcome results are available from CROI 2023.1,21
  • ACTG A5386 (NCT04340596): A Phase 1 trial evaluating the safety and efficacy of N-803 (an investigational therapy based on the cytokine IL-15) administered with and without the bNAbs VRC07-523LS and 10-1074 in controlling viral load during an analytical treatment interruption of ART. This study is currently recruiting participants.22
  • ACTG A5364 (NCT05079451): A Phase 1 trial evaluating the safety and ability of 3BNC117-LS and 10-1074-LS in combination to prevent viral relapse during an analytical treatment interruption. See the ClinicalTrials.gov record for this study’s status.23
  • MCA-1031 (ES38918) (NCT05245292): A Phase 1 trial evaluating the safety and antiretroviral activity of the combination of 3BNC117-LS and 10-1074-LS in addition to N-803 in treatment-experienced adults living with HIV during an analytical treatment interruption. This study is currently recruiting participants.24
  • ANRS 176 RHIVIERA-02 (NCT05300035): A Phase 2 study investigating the safety and efficacy of treatment with 3BNC117-LS and 10-1074-LS in combination with antiretroviral therapy. See the ClinicalTrials.gov record for this study’s status.25

What side effects might 10-1074 cause?What side effects might 10-1074 cause?

What side effects might 10-1074 cause?

One goal of HIV research is to identify new drugs that have fewer side effects. The following side effects were observed in some of the studies of 10-1074 listed above. 

Tatelo Study (NCT03707977)

In this Phase 1/2 trial, results showed that one participant experienced a serious side effect (neutropenia) that was possibly related to study treatment. No participants experienced infusion reactions or life-threatening side effects related to single or dual bNAb administration, and no expedited side effects occurred with dual bNAb treatment.10,26,27

TITAN (NCT03837756)

In this Phase 2a trial, participants were randomly assigned to receive placebo/placebo, lefitolimod/placebo, placebo/bNAbs, or lefitolimod/bNAbs. Two severe side effects occurred. One severe side effect was unrelated to study treatment and the other (infusion reaction) was related to 3BNC117. Mild side effects occurred more frequently in the lefitolimod/bNAbs group than in the other treatment groups.14,15

Because 10-1074 is still being studied, information on possible side effects of the drug is not complete. As testing of 10-1074 continues, additional information on possible side effects will be gathered.

Where can I get more information about clinical trials studying 10-1074?Where can I get more information about clinical trials studying 10-1074?

Where can I get more information about clinical trials studying 10-1074?

More information about 10-1074-related research studies is available from ClinicalTrials.gov. (The ClinicalTrials.gov search can be modified so that you can get results that better match your interests. To learn more about the ClinicalTrials.gov search features, please see How to Search.)

Some clinical trials may be looking for volunteer participants. Your health care provider can help you decide whether participating in a clinical trial is right for you. For more information, visit NIH Clinical Research Trials and You.

ReferencesReferences

References

  1. Treatment Action Group website. Research toward a cure trials. Accessed March 21, 2023
  2. Jefferys R. HIV vaccines & passive immunization. Treatment Action Group Pipeline Report 2022. Accessed March 21, 2023
  3. Gilead Sciences: press release, dated January 9, 2020. Gilead Sciences licenses portfolio of HIV antibodies from The Rockefeller University. Accessed March 21, 2023
  4. HIV Vaccine Trials Network (HVTN). Using antibodies for HIV prevention. Accessed March 21, 2023
  5. Snow B. The rise of broadly neutralizing antibodies. AIDS Vaccine Advocacy Coalition (AVAC). Published May 17, 2018. Accessed March 21, 2023
  6. National Institute of Allergy and Infectious Diseases (NIAID). Sustained ART-free HIV remission. Accessed March 21, 2023
  7. National Institute of Allergy and Infectious Diseases (NIAID). Future directions for HIV treatment research. Accessed March 21, 2023
  8. Grobben M, Stuart RA, van Gils MJ. The potential of engineered antibodies for HIV-1 therapy and cure. Current Opinion in Virology. 2019;38:70-80. doi:10.1016/j.coviro.2019.07.007. Accessed March 21, 2023
  9. National Institute of Allergy and Infectious Diseases (NIAID). A clinical trial to evaluate the impact of broadly neutralizing antibodies VRC01LS and 10-1074 on maintenance of HIV suppression in a cohort of early-treated children in Botswana (dual bNAb treatment in children). In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on October 12, 2018. NLM Identifier: NCT03707977. Accessed March 21, 2023
  10. Shapiro RL, Maswabi K, Ajibola G, et al. Treatment with broadly neutralizing antibodies in children with HIV in Botswana (The Tatelo Study). Webcast presented at: Conference on Retroviruses and Opportunistic Infections (CROI); February 12-16, 2022; Virtual. Accessed March 21, 2023
  11. David Garcia Cinca. A Phase I/IIa, randomised study to evaluate the safety and the effectiveness of a combination of therapeutic vaccine, broadly neutralising antibody (10-1074), and the latency reversing agent romidepsin to achieve a remission of HIV infection in chronically HIV-infected participants under stable combined antiretroviral therapy. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on March 14, 2018. NLM Identifier: NCT03619278. Accessed March 21, 2023
  12. University of California, San Francisco. Combinatorial therapy with a therapeutic conserved element DNA vaccine, MVA vaccine boost, TLR9 agonist and broadly neutralizing antibodies: a proof-of-concept study aimed at inducing an HIV remission. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on April 18, 2020. NLM Identifier: NCT04357821. Accessed March 21, 2023
  13. Peluso M, Deitchman A, Magombedze G, et al. Rebound dynamics following immunotherapy with an HIV vaccine, TLR-9 agonist, and broadly neutralizing antibodies. Poster presented at: Conference on Retroviruses and Opportunistic Infections (CROI); February 19-22, 2023; Seattle, WA. Poster 435. Accessed March 21, 2023
  14. University of Aarhus. Combining a TLR9 agonist with broadly neutralizing antibodies for reservoir reduction and immunological control of HIV infection: an investigator-initiated randomized, placebo-controlled, Phase IIa trial. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on February 7, 2019. NLM Identifier: NCT03837756. Accessed March 21, 2023
  15. Gunst JD, Reikvam DH, McMahon JH, et al. The impact of 3BNC117, 10-1074, and lefitolimod on HIV-1 persistence: the TITAN trial. Abstract presented at: Conference on Retroviruses and Opportunistic Infections (CROI); February 19-22, 2023; Seattle, WA. Abstract 136. Accessed March 21, 2023
  16. Imperial College London. A randomised placebo controlled trial of ART plus dual long-acting HIV-specific broadly neutralising antibodies (bNAbs) vs ART plus placebo in treated primary HIV infection on viral control off ART. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on March 2, 2020. NLM Identifier: NCT04319367. Accessed March 21, 2023
  17. Lee JM, Collins S, Babalis D, et al. The RIO trial: rationale, design, and the role of community involvement in a randomised placebo-controlled trial of antiretroviral therapy plus dual long-acting HIV-specific broadly neutralising antibodies (bNAbs) in participants diagnosed with recent HIV infection—study protocol for a two-stage randomised phase II trial. Trials. 23(1):263. doi:10.1186/s13063-022-06151-w. Accessed March 21, 2023
  18. Rockefeller University. An open label, randomized study of the safety and antiretroviral activity of 3BNC117 and 10-1074 in HIV-infected individuals on combination antiretroviral therapy and during analytical treatment interruption. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on May 3, 2018. NLM Identifier: NCT03526848. Accessed March 21, 2023
  19. Rockefeller University. An open label, single arm study of the safety, pharmacokinetics and antiretroviral activity of the combination of 3BNC117-LS and 10-1074-LS in viremic HIV-infected individuals. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on January 30, 2020. NLM Identifier: NCT04250636. Accessed March 21, 2023
  20. Gilead Sciences. A Phase 1b randomized, blinded, proof-of-concept study to evaluate the safety and efficacy of broadly neutralizing antibodies (bNAbs) GS-5423 and GS-2872 in combination with capsid inhibitor lenacapavir (GS-6207) in virologically suppressed adults with HIV-1 infection. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on March 19, 2021. NLM Identifier: NCT04811040. Accessed March 21, 2023
  21. Luis Montaner. Pilot study on innate activation and viral control in HIV-infected adults undergoing an analytical treatment interruption after administration of pegylated interferon alpha 2b with broadly HIV-1 neutralizing antibodies (3BNC117, 10-1074). In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on April 30, 2018. NLM Identifier: NCT03588715. Accessed March 21, 2023
  22. National Institute of Allergy and Infectious Diseases (NIAID). A Phase I clinical trial of the safety, tolerability, and efficacy of IL-15 superagonist (N-803) with and without combination broadly neutralizing antibodies to induce HIV-1 control during analytic treatment interruption. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on March 23, 2020. NLM Identifier: NCT04340596. Accessed March 21, 2023
  23. National Institute of Allergy and Infectious Diseases (NIAID). A Phase I, open-label study of the safety and ability of broadly neutralizing antibodies 3BNC117-LS and 10-1074-LS in combination to durably prevent viral relapse during a monitored analytical treatment interruption. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on September 2, 2021. NLM Identifier: NCT050709451. Accessed March 21, 2023
  24. Rockefeller University. An open label, single arm study of the safety and antiretroviral activity of two long-acting broadly neutralizing antibodies plus an IL-15 superagonist in ART-treated adults living with HIV during analytical treatment interruption. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on February 8, 2022. NLM Identifier: NCT05245292. Accessed March 21, 2023
  25. ANRS, Emerging Infectious Diseases. A randomised Phase II placebo-controlled trial of antiretroviral therapy (ART) plus dual long-acting HIV-specific broadly neutralising antibodies (bNAbs) vs ART plus placebo during primary HIV-1 infection to study the impact on post-treatment HIV control. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on January 3, 2022. NLM Identifier: NCT05300035. Accessed March 21, 2023
  26. Capparelli EV, Ajibola G, Maswabi K, et al. Safety and pharmacokinetics of intravenous VRC01LS and 10-1074 in young children. Abstract presented at: Conference on Retroviruses and Opportunistic Infections (CROI); March 8-11, 2020; Virtual. Abstract 465. Accessed March 21, 2023
  27. Capparelli EV, Ajibola G, Maswabi K, et al. Safety and pharmacokinetics of VRC01LS and 10-1074 among children in Botswana. Abstract presented at: Conference on Retroviruses and Opportunistic Infections (CROI); March 6-10, 2021; Virtual. Abstract 609. Accessed March 21, 2023
 

Last Reviewed: March 21, 2023