Immunotherapy Rechallenge in Patients with Solid Tumors in Clinical Trials

A Umbrella Study to Evaluate the Safety and Preliminary Efficacy of Combined or Sequential Immunotherapy in Patients with Advanced Solid Tumors Progressing on Clinical Trial Drugs

This study plans to include approximately 60-100 patients with advanced solid tumors who have progressed on clinical trial drugs. It will use an open-label, single-arm, multi-cohort umbrella design. In the first phase, patients who have progressed during treatment with novel tumor immunotherapy drugs will initially be targeted, combining or sequencing with PD-1 monoclonal antibody therapy. The inclusion criteria for frontline clinical trials are as follows: priority will be given to phase I clinical trials of novel immunotherapeutics as monotherapy, such as tumor vaccines, NK cell therapy, and new immune checkpoint inhibitors. Based on preliminary data, these have shown synergistic effects with PD-1/L1 monoclonal antibodies. In principle, the same investigational drug will only be used in either a combination or sequencing cohort. Subsequently, the study will expand to include patients who have progressed on other clinical trial treatments, combining or sequencing with other immune mechanism drugs.

Study Overview

• Status: Recruiting
• Conditions: Cancer
• Intervention / Treatment: Drug: research drug in combination with Toripalimab; Drug: Toripalimab

Detailed Description

This study plans to include approximately 60-100 patients with advanced solid tumors who have progressed on clinical trial drugs, using an open-label, single-arm, multi-cohort umbrella design. In the first phase, patients who have progressed during treatment with novel tumor immunotherapy drugs will initially be targeted, combining or sequencing with PD-1 monoclonal antibody therapy. The selection criteria for frontline clinical trials are as follows: priority will be given to phase I clinical trials of novel immunotherapeutics as monotherapy, such as tumor vaccines, NK cell therapy, and new immune checkpoint inhibitors. Based on preliminary data, these have shown synergistic effects with PD-1/L1 monoclonal antibodies. In principle, the same investigational drug will only be used in either a combination or sequencing cohort. Subsequently, the study will expand to include patients who have progressed on other clinical trial treatments, combining or sequencing with other immune mechanism drugs.

Based on the interventions, the study is divided into combination therapy cohorts, sequential therapy cohorts, and real-world cohorts. The combination therapy cohorts will be further subdivided according to the investigational drug the patients received in the frontline setting: for instance, patients who have progressed on investigational drug A (e.g., SG1827) will receive drug A combined with PD-1 monoclonal antibody therapy (cohort A), and patients who have progressed on investigational drug B (e.g., ABO2011) will receive drug B combined with PD-1 monoclonal antibody therapy (cohort B), and so on. In the sequential therapy cohorts, regardless of the investigational drug used in the frontline setting, patients will receive PD-1 monoclonal antibody therapy. The real-world cohorts will include patients who do not meet the inclusion criteria for the aforementioned cohorts or refuse to participate in the interventional trials, with only subsequent treatment information, tumor progression, and overall survival being collected.

No specific sample size is predetermined for each cohort, and the study team may adjust the cohort sizes based on preliminary study results. In the combination therapy cohorts, the dosage and administration method of the investigational drugs will continue as per the patients' previous trial treatments. In both the combination and sequential therapy cohorts, the PD-1 monoclonal antibody will be administered at a fixed dose of 200 mg every 21 days or 3 mg/kg every 14 days. The treatments will continue until disease progression, death, or the occurrence of intolerable toxicity.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Dawei Wu, Dr.; Phone Number: (+86)-010-87788165; Email: wumingshi-117@163.com

Study Locations

• China
  • Beijing, China
    • Recruiting
    • Cancer Institute and Hospital, Chinese Academy of Medical Sciences
    • Contact: Ning li
    • Contact: Ning Li; Phone Number: 010-87788495; Email: cancergcp@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Recurrent or metastatic solid tumors confirmed by histopathology that cannot be treated with curative local therapy
2. Prior systemic anti-tumor treatment requirements: Previous first-line treatment involved a clinical trial of a new drug, with disease progression, and deemed by the investigator to no longer benefit from it
3. Suggested first dose administered within 12 weeks after the last treatment.
4. According to the RECIST 1.1 criteria, there should be at least one measurable lesion or more
5. ECOG PS 0-2 points
6. expected survival ≥ 3 months
7. as assessed by the investigator, major organ functions are good enough and can tolerate the experimental treatment regimen used in this study
8. subjects can understand and comply with the study procedures, sign the informed consent form, and voluntarily participate in this study
9. patients included in the real-world cohort who do not meet the aforementioned inclusion criteria or refuse to participate in the aforementioned interventional experimental treatment

Exclusion Criteria:

1. Previous exposure to immunotherapy (standard treatment or clinical trials) resulted in severe immune-related adverse events, as assessed by the investigator, making the re-administration of immunotherapy inappropriate.
2. Previous adverse reactions to advanced solid tumors have persisted, and the investigator anticipates these might impact the safety evaluation of the investigational drug
3. Previously experienced hyperprogression during immune therapy (conventional treatment or clinical trials), and the Other conditions deemed unsuitable for participation in this study by the investigator believes that no further benefit can be gained from this study. Criteria include: (1) Tumor progression time less than two months during immunotherapy
4. (2) Tumor burden increased by over 50% compared to baseline
5. (3) Tumor growth rate post-immunotherapy exceeds twice the previous rate
6. Central nervous system metastases or leptomeningeal metastases with clinical symptoms
7. During the screening period, subjects are determined by the investigator to have severe or uncontrolled underlying diseases (such as hypertension, diabetes, cardiovascular diseases, pulmonary diseases, autoimmune diseases, etc.)
8. Received other anti-tumor therapy between the last front-line therapy and the first dose of the study drug
9. Other conditions deemed unsuitable for participation in this study by the investigator

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Combination therapy; Research drug in combination with Toripalimab	Drug: research drug in combination with Toripalimab; research drug in combination with Toripalimab
Experimental: Sequential therapy; Toripalimab	Drug: Toripalimab; Toripalimab
No Intervention: RWS cohort; observation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Experiencing AEs	Number of participants with AE by CTCAE v5.0.	5 years
Number of Participants Experiencing TEAEs	Number of Participants with TEAEs by CTCAE v5.0.	5 years
Number of Participants Experiencing TRAEs	Number of Participants with TRAEs by CTCAE v5.0.	5 years
Number of Participants Experiencing SAEs	Number of Participants with SAEs by CTCAE v5.0.	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR)	Overall Response Rate (ORR)	5 years
Disease Control Rate(DCR) Disease Control Rate(DCR) Disease Control Rate(DCR) Disease Control Rate(DCR)	Disease Control Rate(DCR)	5 years
Duration of Response (DOR)	Duration of Response (DOR)	5 years
Progression-Free Survival (PFS)	Progression-Free Survival (PFS)	5 years
Overall Survival (OS)	Overall Survival (OS)	5 years

Collaborators and Investigators

• Sponsor: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
• Investigators: Principal Investigator: Ning Li, Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Study record dates

Study Major Dates

• Study Start (Actual): May 24, 2024
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2028

Study Registration Dates

• First Submitted: July 14, 2024
• First Submitted That Met QC Criteria: September 23, 2024
• First Posted (Actual): September 25, 2024

Study Record Updates

• Last Update Posted (Actual): September 25, 2024
• Last Update Submitted That Met QC Criteria: September 23, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: immunotherapy; solid tumor; rechallenge; clinical trail
• Other Study ID Numbers: NCC20231105

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Academic papers publishing research results

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No