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Autologous B7-H3 Chimeric Antigen Receptor T Cells in Previously Treated Extensive-Stage Small Cell Lung Cancer With Recurrent or Refractory Disease

ConditionsRecurrent Small Cell Lung CancerExtensive-Stage Small Cell Lung CancerSmall Cell Lung CancerSmall Cell Lung CarcinomaRefractory Small Cell Lung CancerExtrapulmonary Small Cell CarcinomaNeuroendocrine CarcinomaPoorly Differentiated Neuroendocrine CarcinomaHigh-Grade Neuroendocrine Carcinoma
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18-120
SponsorNational Cancer Institute (NCI)

About this trial

Background:

Small cell lung cancer (SCLC) is the deadliest form of lung cancer. Extrapulmonary neuroendocrine cancer (EPNEC) is a similar type of cancer that develops anywhere other than the lungs. EPNEC is also deadly. B7-H3 is a protein often found in SCLC and EPNEC tumor cells. Researchers can modify a person s own T cells, or immune cells, to target B7-H3. When these modified T cells are returned to the body-a treatment called B7-H3 chimeric antigen receptor (CAR) T cell therapy-they may help kill cancer cells.

Objective:

To test B7-H3 CAR T cell therapy in people with SCLC or EPNEC.

Eligibility:

People aged 18 years and older with SCLC or EPNEC that either did not respond or returned after treatment.

Design:

Participants will be screened. They will have blood tests and tests of their heart function. They will have imaging scans.

Participants will undergo apheresis: Blood will be taken from the body through a needle. The blood will pass through a machine that separates out the T cells. The remaining blood will be returned to the body through a different needle. The collected T cells will be altered to make them attack cells with B7-H3.

Participants will be in the hospital for at least 15 days. They will receive chemotherapy drugs to prepare their body for the treatment. These drugs will be given through a tube attached to a needle inserted into a vein.

The modified T cells will be infused through a vein. Participants will remain in the hospital until they are well enough to go home.

Follow-up visits will continue for 15 years....

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Age >=18 years old.

Histologically confirmed small cell lung cancer (SCLC) or extrapulmonary neuroendocrine cancers (EP-NEC) that has recurred following or is refractory to first-line therapy. Note: small cell cancers of non-lung primary sites are also eligible.

Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-2.

Pulse oximetry >= 90% on room air.

Disqualifiers

History of anaphylactic reactions attributed to anti-B7-H3 antibodies or compounds of similar chemical or biologic composition to autologous B7-H3 CAR T cells, cyclophosphamide, fludarabine, or other agents used in this study.

Positive serology for HIV.

Active HBV infection as demonstrated by test for hepatitis B surface antigen (HBsAg).

Positive serology for HCV.

Trial design

Design model

Sequential

Treatments tested in this trial

  • Autologous B7-H3 CAR T

    Drug

    For both dose escalation and expansion phases, B7-H3 CAR T cell infusion will be performed following lymphodepleting therapy. Up to 2 years post the initial infusion, participants will be offered the option for an additional infusion of B7-H3 CAR T cells at the same dose level as the initial dose, with or without LD if eligible.

  • Cyclophosphamide

    Drug

    For both dose escalation and expansion phases, FDA approved lymphodepleting agents, cyclophosphamide and fludarabine will be used on this study prior to the administration of T cells.

  • Fludarabine

    Drug

    For both dose escalation and expansion phases, FDA approved lymphodepleting agents, cyclophosphamide and fludarabine will be used on this study prior to the administration of T cells.

Treatment groups

40 Participants
are divided into 2 treatment groups
Group A: Dose EscalationExperimental treatment 3 interventions
Group B: Dose ExpansionExperimental treatment 3 interventions

Trial outcomes

Primary outcomes

1

Determine the maximum tolerated dose (MTD) or maximum administered dose (MAD) of autologous B7-H3 CAR T cells

The MTD/MAD is the dose level at which no more than 1 of up to 6 participants experience DLT during autologous B7-H3 CAR T cell treatment, and the dose below that at which at least 2 (of \<=6) participants have DLT as a result of treatment.

Time frame
Dose Limiting Toxicity (DLT) period (day 0 through day 28)
2

Determine disease control rate (DCR)

DCR will be reported as a percentage of participants who achieve a complete response, partial response, or stable disease following autologous B7-H3 CAR T cells treatment.

Time frame
Until disease progression or 15 years, whichever occurs first

Secondary outcomes

1

Assess safety of autologous B7-H3 CAR T cells infusion

Safety will be reported based on the number (percentage) of participants experiencing adverse events per dose level as well as reporting specific grades and types of toxicity encountered per the Common Terminology Criteria for Adverse Events (CTCAE) version 6.0.

Time frame
Study duration
2

Objective Response Rate (ORR)

The ORR will be reported among 13-16 participants, which includes both participants treated at the MTD/MAD during the dose escalation phase (3-6 participants) and the 10 participants treated during the dose expansion phase, along with a 95% two-sided confidence interval.

Time frame
Until disease progression or 15 years, whichever occurs first
3

Duration of Response (DOR)

DOR will be reported using a Kaplan-Meier curve and 95% confidence interval for the median of each based on the participants at the final dose level.

Time frame
Until disease progression or 15 years, whichever occurs first
4

Progression Free Survival (PFS)

PFS will be reported using a Kaplan-Meier curve and 95% confidence interval for the median of each based on the participants at the final dose level.

Time frame
Until disease progression or 15 years, whichever occurs first

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

National Cancer Institute (NCI)

Lead sponsor

Source ClinicalTrials.gov
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