Phase 2
Completed N=62
Platform Trial of Novel Regimens Versus Standard of Care (SoC) in Participants With Non-small Cell Lung Cancer (NSCLC) - Sub-study 3
Neoplasms
Source: ClinicalTrials.gov NCT06926673 ↗
Enrolled (actual)
62
Serious AEs
27.4%
Results posted
Jul 2025
Primary outcomePrimary: Part 1: Number of Participants With Any Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) (Arm 4) — 6; 9; 8; 0 Participants
Summary
This study is a sub-study of the master protocol 205801 (NCT03739710). This sub study will assess safety and pharmacokinetics and pharmacodynamics (PK/PD) of novel regimens (Dostarlimab plus belrestotug , and Dostarlimab plus belrestotug plus nelistotug) in participants with previously treated NSCLC.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Part 1: Number of Participants With Any Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) (Arm 4) |
6; 9; 8; 0; 3; 2 | — |
| PRIMARY Part 1: Number of Participants With Any TEAEs and SAEs (Arm 5) |
10; 6; 11; 9; 3; 3 | — |
| PRIMARY Part 1: Number of Participants With Dose Limiting Toxicity (DLT) (Arm 4 and Arm 5) |
0; 0; 0; 1 | — |
| PRIMARY Part 1: Number of Participants Requiring Dose Modifications (Arm 4) |
0; 3; 2; 0; 1; 1 | — |
| PRIMARY Part 1: Number of Participants Requiring Dose Modifications (Arm 5) |
6; 2; 5; 6; 1; 0 | — |
| PRIMARY Part 1: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status (Arm 4) |
0; 5; 3; 6; 4; 6 | — |
| PRIMARY Part 1: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status (Arm 5) |
4; 2; 7; 1; 6; 5 | — |
| PRIMARY Part 1: Number of Participants With Worst-case Post Baseline Increase From Baseline in Vital Signs (Arm 4) |
0; 2; 2; 0; 1; 0 | — |
| PRIMARY Part 1: Number of Participants With Worst-case Post Baseline Increase From Baseline in Vital Signs (Arm 5) |
5; 1; 4; 5; 3; 0 | — |
| PRIMARY Part 1: Number of Participants Who Received Concomitant Medications (Arm 4) |
6; 9; 9 | — |
| PRIMARY Part 1: Number of Participants Who Received Concomitant Medications (Arm 5) |
10; 7; 11; 10 | — |
| PRIMARY Part 1: Number of Participants With Worst-case Post Baseline Relative to Baseline Electrocardiogram (ECG) Findings (Arm 4) |
4; 2; 4; 2; 6; 3 | — |
| PRIMARY Part 1: Number of Participants With Worst-case Post Baseline Relative to Baseline ECG Findings (Arm 5) |
5; 5; 5; 7; 4; 1 | — |
| PRIMARY Part 1: Number of Participants With Worst-case Post Baseline Relative to Baseline in QTcF Interval (Arm 4) |
4; 6; 8; 1; 0; 0 | — |
| PRIMARY Part 1: Number of Participants With Worst-case Post Baseline Relative to Baseline in QTcF Interval (Arm 5) |
10; 6; 10; 9; 0; 1 | — |
| PRIMARY Part 1: Number of Participants With Worst-case Post Baseline Relative to Baseline in Left Ventricular Ejection Fraction (LVEF) (Arm 4) |
1; 0; 0; 0; 0; 0 | — |
| PRIMARY Part 1: Number of Participants With Worst-case Post Baseline Relative to Baseline in Left Ventricular Ejection Fraction (LVEF) (Arm 5) |
2; 0; 0; 0; 2; 1 | — |
| PRIMARY Part 1: Number of Participants With Worst Case Hematology Results by Maximum Grade Increase Post-Baseline Relative to Baseline (Arm 4) |
1; 2; 0; 0; 0; 0 | — |
| PRIMARY Part 1: Number of Participants With Worst Case Hematology Results by Maximum Grade Increase Post-Baseline Relative to Baseline (Arm 5) |
1; 2; 3; 3; 0; 0 | — |
| PRIMARY Part 1: Number of Participants With Worst Case Clinical Chemistry Results by Maximum Grade Increase Post-Baseline Relative to Baseline (Arm 4) |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Part 1: Number of Participants With Worst Case Clinical Chemistry Results by Maximum Grade Increase Post-Baseline Relative to Baseline (Arm 5) |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Part 1: Number of Participants With Worst Case Change Post-baseline in Clinical Chemistry Parameters (Arm 4) |
0; 1; 1; 0; 0; 0 | — |
| PRIMARY Part 1: Number of Participants With Worst Case Change Post-baseline in Clinical Chemistry Parameters (Arm 5) |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Part 1: Number of Participants With Worst-Case Urinalysis Results Post-Baseline Relative to Baseline (Arm 4) |
4; 6; 7; 1; 1; 1 | — |
| PRIMARY Part 1: Number of Participants With Worst-Case Urinalysis Results Post-Baseline Relative to Baseline (Arm 5) |
4; 5; 6; 6; 4; 0 | — |
| PRIMARY Part 2: Overall Survival (OS) |
— | — |
| SECONDARY Part 1: Objective Response Rate (ORR) (Arm 4) |
0; 0; 0 | — |
| SECONDARY Part 1: Objective Response Rate (ORR) (Arm 5) |
0; 0; 9; 0 | — |
| SECONDARY Part 1: Disease Control Rate (DCR) (Arm 4) |
17; 22; 11 | — |
| SECONDARY Part 1: Disease Control Rate (DCR) (Arm 5) |
40; 14; 27; 0 | — |
| SECONDARY Part 1: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of Belrestotug (Arm 4) |
88.470; 118.762; 271.835; 9.412; 22.091; 44.350 | — |
| SECONDARY Part 1: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of Belrestotug (Arm 5) |
126.386; 137.837; 153.377; 22.967; 19.408; 20.752 | — |
| SECONDARY Part 1: Cmax and Cmin of Dostarlimab (Arm 4) |
119.400; 124.278; 97.433; 33.900; 34.071; 22.935 | — |
| SECONDARY Part 1: Cmax and Cmin of Dostarlimab (Arm 5) |
108.920; 126.857; 68.751; 109.330; 29.290; 34.550 | — |
| SECONDARY Part 1: Cmax and Cmin of Nelistotug (Arm 5) |
299.889; 479.714; 75.580; 554.750; 43.689; 88.243 | — |
| SECONDARY Part 2: Survival Rate at 12 and 18 Months |
— | — |
| SECONDARY Part 2: Number of Participants With Complete Response (CR), Partial Response (PR), Stable Disease (SD) and Progressive Disease (PD) |
— | — |
| SECONDARY Part 2: Progression-free Survival (PFS) |
— | — |
| SECONDARY Part 2: Objective Response Rate (ORR) |
— | — |
| SECONDARY Part 2: Duration of Response (DOR) |
— | — |
| SECONDARY Part 2: Disease Control Rate (DCR) |
— | — |
| SECONDARY Part 2: Number of Participants With Immune-based (i) Complete Response (iCR), Partial Response (iPR), Unconfirmed Progressive Disease (iUPD), Confirmed Progressive Disease (iCPD), and Stable Disease (iSD) |
— | — |
| SECONDARY Part 2: Progression-free Survival (iPFS) |
— | — |
| SECONDARY Part 2: Objective Response Rate (iORR) |
— | — |
| SECONDARY Part 2: Duration of Response (iDOR) |
— | — |
| SECONDARY Part 2: Number of Participants With AEs, SAEs, Adverse Events of Special Interest (AESI), AE/SAEs Leading to Dose Modifications/Delays/Withdrawals |
— | — |
| SECONDARY Part 2: Number of Participants With Clinically Significant Changes in Vital Signs and Laboratory Parameters |
— | — |
| SECONDARY Part 2: Cmax and Cmin for Dostarlimab |
— | — |
| SECONDARY Part 2: Cmax and Cmin for Belrestotug |
— | — |
| SECONDARY Part 2: Number of Participants With Positive Anti-drug Antibodies (ADA) |
— | — |
Eligibility Criteria
Inclusion Criteria
- Participants capable of giving signed informed consent/assent.
- Male or female, aged 18 years or older at the time consent is obtained.
- Participants with histologically or cytologically confirmed diagnosis of NSCLC (squamous or non-squamous) and
- Documented disease progression based on radiographic imaging, during or after a maximum of 2 lines of systemic treatment for locally/regionally advanced recurrent, Stage IIIb/Stage IIIc/Stage IV or metastatic disease. Two components of treatment must have been received in the same line or as separate lines of therapy: i) No more than or less than 1 line of platinum-containing chemotherapy regimen, and ii) No more than or less than 1 line of Programmed cell death ligand 1 (PD[L]1) monoclonal antibody (mAb) containing regimen.
- Participants with known V-Raf Murine Sarcoma Viral Oncogene Homolog B (BRAF) molecular alterations must have had disease progression after receiving the locally available SoC treatment for the molecular alteration.
- Participants who received prior anti-PD(L)1 therapy must fulfill the following requirements: i) Have achieved a CR, PR or SD and subsequently had disease progression (per RECIST 1.1 criteria) either on or after completing PD(L)1 therapy ii) Have not progressed or recurred within the first 12 weeks of PD(L)1 therapy, either clinically or per RECIST 1.1 criteria
- Measurable disease, presenting with at least 1 measurable lesion per RECIST 1.1.
- Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0 or 1.
- A tumor tissue sample obtained at any time from the initial diagnosis of NSCLC to time of study entry is mandatory. Although a fresh tumor tissue sample obtained during screening is preferred, archival tumor specimen is acceptable.
- Adequate organ function as defined in the protocol.
- A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least 1 of the following conditions apply:
i) Not a woman of childbearing potential (WOCBP) as defined in the protocol or ii) A WOCBP who agrees to follow the protocol defined contraceptive guidance during the treatment period and for at least 120 days after the last dose of study treatment.
- Life expectancy of at least 12 weeks.
Exclusion Criteria
Participants who received prior treatment with the following therapies (calculation is based on date of last therapy to date of first dose of study treatment):
- Docetaxel at any time.
- Any of the investigational agents being tested in the current study.
- Systemic approved or investigational anticancer therapy within 30 days or 5 half-lives of the drug, whichever is shorter. At least 14 days must have elapsed between the last dose of prior anticancer agent and the first dose of study drug administered.
- Prior radiation therapy: permissible if at least one non-irradiated measurable lesion is available for assessment per RECIST version 1.1 or if a solitary measurable lesion was irradiated, objective progression is documented. A wash out of at least 2 weeks before start of study drug for radiation of any intended use is required.
- Received greater than (>) 2 prior lines of therapy for NSCLC, including participants with BRAF molecular alternations.
- Invasive malignancy or history of invasive malignancy other than disease under study within the last 2 years.
- Carcinomatous meningitis (regardless of clinical status) and uncontrolled or symptomatic Central nervous system (CNS) metastases.
- Major surgery less than or equal to ( 10 milligrams [mg]) oral prednisone or equivalent) or other immunosuppressive agents within 7 days prior to first dose of study treatment. Steroids as premedication for hypersensitivity reactions (e.g., computed tomography [CT] scan premedication) are permitted.
- Prior allogeneic/autologous bone marrow or solid organ transplantation.
- Receipt of any live vaccine within 30 days prior to first dose of study treatment.
- Toxicity from previo
Data sourced from ClinicalTrials.gov (NCT06926673). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.